Presentation Outline ICHP Annual Meeting September 13-15

ACTIVITY DESCRIPTION 

Target Audience 

This continuing pharmacy education activity is planned to meet the need of 

pharmacists in a variety of practice settings, including large and small health 

systems, outpatient clinics, managed-care organizations, long-term care 

facilities, and academia. This program will target health-system pharmacists 

who are responsible for the safe and effective use of medications utilized for the 

treatment of patients with PAH. 

Learning Objectives 

Upon completing this program, participants will be able to: 

• Discuss the pathophysiology of PAH 

• Compare the safety and efficacy among the various classes of medications 

used in the treatment of PAH 

• Utilize evidence-based guidelines to select appropriate therapy to meet 

individualized patient treatment goals 

ACCREDITATION 

Pharmacists 

Center for Independent Healthcare Education (Center) is accredited by 

the Accreditation Council for Pharmacy Education as a provider of 

continuing pharmacy education. Center has assigned 1.5 contact hours 

(0.15 CEUs) for this activity. 

ACPE Universal Activity Number: 473-999-12-004-L01-P 

Type of Activity: Knowledge-based 

Instructions for Credit 

To receive a Statement of Credit, participants must register for the symposium, 

document attendance, and complete and return the evaluation form. A Statement 

of Credit will be mailed to you 4 weeks after the symposium. 

1

Roberto F. Machado, MD 

Associate Professor of Medicine 

Section of Pulmonary, Critical Care 

Medicine, Sleep and Allergy 

FACULTY 

Heather R. Bream-Rouwenhorst, 

PharmD, BCPS 

Clinical Assistant Professor 

University of Iowa College of Pharmacy 

Clinical Pharmacy Specialist–Cardiology 

U i it f I H it l & Cli i 

Iowa City, IA 

Institute for Personalized 

RRespiratory i t MMedicine di i University of Iowa Hospitals & Clinics 

University of Illinois at Chicago 

College of Medicine 

Chicago, IL 

James C. Coons, PharmD, BCPS 

(AQ Cardiology) 

Associate Professor 

University of Pittsburgh School of 

Pharmacy 

Department of Pharmacy & Therapeutics 

Pittsburgh, PA 

DISCLOSURES 

Planning Committee Members 

Heather R. Bream-Rouwenhorst, PharmD, BCPS Paul DeLisle 

James C. Coons PharmD, BCPS (AQ Cardiology) Marco Cicero, PhD 

Roberto F. Machado, MD Maja Drenovac, PharmD 

Disclosure of Financial Interest Summary 

Heather R. Bream-Rouwenhorst, PharmD (faculty) has no relevant financial relationships with commercial 

interests. 

Dr Dr. Bream-Rouwenhorst Bream Rouwenhorst does not intend to discuss the off-label off label use of a product product. 

James C. Coons, PharmD (faculty) has no relevant financial relationships with commercial interests. 

Dr. Coons does not intend to discuss the off-label use of a product. 

Roberto F. Machado, MD (faculty) has relevant financial relationships with commercial interests as follows: 

Advisory Board: Gilead Sciences 

Grant Recipient/Research Support: NIH, Actelion, United Therapeutics 

Dr. Machado does intend to discuss imatinib for PAH treatment. 

No (other) speakers, authors, planners or content reviewers have any relevant financial relationships 

to disclose. No (other) speakers or authors will discuss off-label use of a product. 

Content review confirmed that the content was developed in a fair, balanced manner free from 

commercial bias. Disclosure of a relationship is not intended to suggest or condone commercial bias in 

any presentation, but it is made to provide participants with information that might be of potential 

importance to their evaluation of a presentation. 

Major Issues and Challenges of 

Hospital Pharmacists When 

Managing Patients with PAH 


(AQ-Cardiology) 


University of Pittsburgh School of Pharmacy 

Department of Pharmacy and Therapeutics 

Pittsburg, PA 

2

Current Challenges 

• Expansion of therapeutic options 

– Medications 

– Delivery systems 

• Complexity of regimens 

• High-risk medications 

• Patient acuity 

• Educational needs 

Pharmacotherapy Timeline 

• 1960-1980…empiric/various vasodilators 

• 1980… oral anticoagulants, calcium channel 

blockers, lung/heart transplantation 

• 1996… epoprostenol 

• 2001… bosentan 

• 2002… treprostinil subcutaneous (SC) 

• 2004… treprostinil intravenous (IV), iloprost 

• 2005… sildenafil 

• 2007… ambrisentan 

• 2009… tadalafil, treprostinil inhaled 

• 2010… thermostable epoprostenol 

Evaluating Prostacyclin Safety 

• Surveys of PAH centers 

– University Hospital Consortium (UHC) 

– Phone interview – 18 large PAH centers 

– Electronic ec o c su survey ey – convenience co e e ce sa sample p e oof aall 

PAH centers in US (n=97) 

Kingman MS, et al. J Heart Lung Transplant. 2010;29:841-846. 

3

Findings and Scope of Problem 

• UHC and phone interviews 

– Baseline evaluation of policies 

• 8 of 18 kept patients on their home pumps 

• 10 of 18 patients did not keep back-up prostacyclin 

cassettes on the unit 



• Phone interview 

– Serious errors at 17 of 18 centers 

• Failure to restart CADD pump 

• Wrong patient 

• Wrong rate 

• Errors in dose calculations 

• Flushing of the prostacyclin line 

– 3 deaths 

CADD, computerized ambulatory drug delivery 



• Electronic survey 

– Serious or potentially serious errors – 68% 

• Wrong patient 

• Wrong dose 

• Pump left off 

• Flushing the line 

– 9 deaths 


4

Examples of Medication Considerations 

Treprostinil 

• Multiple vial concentrations 

– 1, 2.5, 5, & 10 mg/mL 

• Multiple routes of administration 

– IV, SC, inhaled 

• Multiple delivery systems 

– IV – CADD infusion pump, Crono-5 pump 

– SC – CADD-MS3 & MiniMed syringe pumps 

– Inhaled – Tyvaso inhalation system ® 

Examples of Medication Considerations 

Epoprostenol 

• Requires reconstitution 

• Requires back-up cassette 

• Multiple formulations 

– Epoprostenol (Flolan ® ) 

– Generic epoprostenol 

– “Room-temperature stable” epoprostenol 

(Veletri ® ) 

Knowing the Pharmacist’s Role in 

Managing PAH 

Pathophysiology of PAH 

Heather R. Bream-Rouwenhorst, 

PharmD, BCPS 



Clinical Pharmacy Specialist – Cardiology 

University of Iowa Hospitals and Clinics 

Iowa City, IA 

5

• Etiology 

• Epidemiology 

• PPathophysiology th h i l 

Overview 

Definition 

• Mean pulmonary artery pressure (mPAP) >25 

mmHg at rest in setting of: 

– Normal or decreased cardiac output 

– Normal fluid status 

Badesch DB, et al. J Am Coll Cardiol. 2009;54(1 Suppl):S55. 

1. Pulmonary 

arterial 

hypertension 

Etiology (Dana Point, 2008) 

1.1 Idiopathic 

1.2 Heritable 1.2.1 BMPR2 1.2.2 ALK1, endoglin 

1.2.3 Unknown 

1.3 Drug/toxin-induced 

1.4 Associated with 1.4.1 Connective tissue disease 

1.4.2 HIV infection 

1.4.3 Portal hypertension 

1.4.4 Congenital heart disease 

1.4.5 Schistosomiasis 

1.4.6 Chronic hemolytic anemia 

1.5 Persistent pulmonary 

hypertension of the 

newborn 

Simonneau G, et al. J Am Coll Cardiol. 2009;54(1s1):S43-54. 

6


1’. Pulmonary veno-occlusive disease 

(PVOD) and/or pulmonary capillary 

hemangiomatosis (PCH) 

2. PH due to left heart disease 2.1 Systolic dysfunction 

2.2 Diastolic dysfunction 

2.3 3 Valvular a u a disease d sease 

3. PH due to lung diseases and/or 3.1 COPD 

hypoxia 

3.2 Interstitial lung disease 

3.3 Other pulmonary diseases with 

mixed restrictive and obstructive pattern 

3.4 Sleep-disordered breathing 

3.5 Alveolar hypoventilation disorders 

3.6 Chronic exposure to high altitude 

3.7 Developmental abnormalities 



4. CTEPH 

5. PH with unclear 5.1 Hematologic Myeloproliferative disorders 

multifactorial 

mechanisms 

disorders 

5.2 Systemic 

Splenectomy 

Sarcoidosis 

disorders 

Pulmonary Langerhans cell histiocytosis 

LLymphangioleiomyomatosis h i l i t i 

Neurofibromatosis type 1 

Vasculitis 

5.3 Metabolic Glycogen storage disease 

disorders 

Gaucher disease 

Thyroid disorders 

5.4 Others Tumoral obstruction 

Fibrosing mediastinitis 

CKD on dialysis 


Epidemiology 

• PAH prevalence1 – Estimated 50,000–100,000 Americans 

– 15,000–20,000 diagnosed and receiving 

treatment 

• Diagnosed typically 3rd –4th decade of life2 • Female:male ratio 1.7:1 

• 2.8-year median survival without treatment3 1 DeMarco T. Cardiol Rev. 2006;14:312–8. 

2 Rich S, et al. Ann Intern Med. 1987;107:216-23. 

3 D’Alonzo GE, et al. Ann Intern Med. 1991;115:343-9. 

7

Mean Survival by Etiology 

CHD, congenital heart disease; CTD, connective tissue disease; IPAH, idiopathic pulmonary arterial hypertension; 

Portopulm, portopulmonary hypertension 

McLaughlin VV, et al. J Am Coll Cardiol. 2009;53:1573-1619. 

Pathophysiology 

Normal PAH 


Pathophysiology 

• Endothelin-1 

• Nitric oxide 

• Prostacyclin 

Serotonin 

• Serotonin 

• Vasoactive intestinal peptide (VIP) 

• Inflammation 

8

PAH Therapy Targets 

Schulze-Neick I, Beghetti M. Eur Respir Rev. 2010;19:331–9. 

Serotonin 

• Effects 

– Vasoconstriction 

– Smooth muscle cell hyperplasia and hypertrophy 

• Impaired platelet serotonin storage in PAH 

– Dexfenfluramine 

• No PAH-SSRI association 

McLaughlin VV, et al. Curr Probl Cardiol. 2011;36:461-517. 

Marcos E, et al. Am J Respir Crit Care Med. 2003;168:487-93. 

VIP 

• Effects 

– Vasodilatation 

– Inhibition of vascular smooth muscle cell 

proliferation 

• Low levels in PAH population 

McLaughlin VV, et al. Curr Probl Cardiol. 2011;36:461-517. 

9


Managing PAH 

Knowing Your Therapeutic Options: 

Current Medications and Their 

Effectiveness 



Section of Pulmonary, Critical Care Medicine, 

Sleep and Allergy 

Institute for Personalized Respiratory Medicine 

University of Illinois at Chicago College of Medicine 

Chicago, IL 

PAH Treatment Goals 

• Fewer/less severe symptoms 

• Improved exercise capacity 

• Improved hemodynamics 

• Prevention of clinical worsening 

• Improved quality of life 

• Improved survival 

What Is the Optimal Treatment Strategy? 

Anticoagulate ± Diuretics ± 

Oxygen ± Digoxin 

Oral CCB 

Sustained 

Response 

Yes 

Continue 

CCB 

Positive 

Acute Vasoreactivity Testing 

Negative 

No LOWER RISK DETERMINANTS OF RISK HIGHER RISK 

No Clinical evidence of RV failure Yes 

Gradual Progression of symptoms Rapid 

II, III WHO class IV 

Longer (>400 m) 6MWD Shorter (10.4 mL/kg/min CPET Peak VO2 20 mm Hg; 

CI

Chronic Adjuvant Therapies in PAH 

Digoxin 

• Variable inotropic effect and use 

• No long-term data; need to balance unproven benefits with known risks 

Oxygen 

• Use to prevent hypoxic vasoconstriction 

• Consider exercise, sleep, altitude 

• Aim for target saturation >90% 

• May not correct hypoxia with shunt 

Diuretics 

• Most need; hypotension not a contraindication (may need BP support) 

• Renal function and electrolytes must be monitored closely 

Anticoagulation 

• Recommended in IPAH 

• Retrospective data only; need to balance unproven benefits with known risks 

• INR 1.5–2.5 

Adapted from: Badesch DB, et al. Chest. 2004;126:35S-62S. 

Badesch DB, et al. Chest. 2007;131:1917-1928. 


Other Management Issues 

• Encourage exercise and activity within the limits 

of disease and ability to maintain O2 levels 

• Immunizations 

• Contraception 




Oral CCB 

Sustained 

Response 

Yes 

Continue 

CCB 

Positive 


Negative 






CI

Criteria for “Responders” 

Criteria for Long-term Beneficial Effect of CCB? 

557 consecutive IPAH 

70 acute responders (12.6%) 487 non-responders (87.4%) 

38 long-term CCB responders (6.8%) 32 long-term CCB failures 

CCB, calcium-channel blocker 

Sitbon O, et al. Circulation. 2005;111:3105-3111. 

93.2% “non-responders” 

• Acute vasodilator testing with PgI2 (n=156) or NO (n=401) 

• Acute response = fall in mPAP and PVR >20% � initiation of 

chronic CCB 

• Long-term CCB responders = NYHA FC I/II after at least one 

year on oral CCB without need for prostanoids and/or ERAs 

Revised Definition of 

Vasodilator Responder 

“Vasodilator Response” 

• Fall in mPAP ≥10 mmHg 

• + mPAP (absolute) ( )

Cummulative 

suurvival 

Survival in IPAH 

Long-term CCB Responders 

1.0 

0.8 

0.6 

04 0.4 

0.2 

0.0 

Subjects 

at risk, n 

Long-term CCB responders (~50% of acute 

responders or ≤6% of IPAH patients) 

p=0.0007 

Long-term CCB failure 

0 2 4 6 8 10 12 14 16 18 

Years 

38 33 30 22 13 8 3 3 2 1 

19 12 7 4 0 

Sitbon O, et al. Circulation. 2005;111:3105-3111. 

Long-term CCB 

responders 

Long-term CCB 

failure 




Oral CCB 

Positive 



Negative 



Sustained 


Response 



CI 400 ( m) ) 6MWD Shorter (10.4 mL/kg/min CPET Peak VO 2 20 mm Hg; 

CI

Key Pathways Implicated in PAH Pathogenesis 

Endothelin 

Pathway 

Pre-proendothelin 

Endothelin 

receptor A 

Endothelin Endothelin-11 

Smooth muscle cells 

Proendothelin 

Endothelin 

receptor B 

Vasoconstriction 

and proliferation 

Endothelial cells 

Humbert M, et al. N Engl J Med. 2004;351:1425-1436. 

Nitric Oxide 

Pathway 

L-arginine 

Nitric Oxide 

cGMP 

L-citrulline 

Phosphodiesterase 

type 5 Vasodilation 

and antiproliferation 


Prostacyclin 

Pathway 

Arachidonic acid 

Prostaglandin I 2 

Prostacyclin (prostaglandin I I2) ) 

cAMP 

Vasodilation 



Key Pathways Implicated in PAH Pathogenesis 

Endothelin 

Pathway 


Endothelin 

receptor A 




Proendothelin 



Endothelin 

receptor A 

Endothelinreceptor 

antagonists 

Endothelin 

receptor B 



Nitric Oxide 

Pathway 

L-arginine 

Nitric Oxide 

cGMP 

L-citrulline 


type 5 Vasodilation 


Prostacyclin 

Pathway 





cAMP 

Vasodilation 



Mechanisms of Action of 

Approved Therapies for PAH 

Endothelin 

Pathway 




Proendothelin 

Endothelin 

receptor B 




Nitric Oxide 

Pathway 

L-arginine 


type 5 

Nitric Oxide 

cGMP 

L-citrulline 

Prostacyclin 

Pathway 



Exogenous 

nitric oxide 

Vasodilation 



type 5 inhibitor 



cAMP 

Vasodilation 



Prostacyclin 

derivatives 

14

ACCF/AHA Consensus PAH Treatment 

Algorithm 



Oral CCB 

Sustained 

Response 

Yes 

Continue 

CCB 

No 

Positive 

Modified from McLaughlin VV, et al. J Am Coll Cardiol. 2009;53:1573-1619. 


Endothelin 

receptor A 


antagonists 


Negative 

Lower Risk Higher Risk 

ERAs or PDE-5 Is (oral) 

Epoprostenol or Treprostinil (IV) 

Iloprost (inhaled) 

Treprostinil (SC, inhaled) 

Reassess: consider 

combo-therapy 

Investigational Protocols 

Epoprostenol or Treprostinil (IV) 

Iloprost (inhaled) 

ERAs or PDE-5 Is (oral) 

Treprostinil (SC) 

Atrial septostomy 

Lung transplant 

Approved Therapeutic Targets 

Endothelin 

Pathway 




Proendothelin 

Endothelin 

receptor B 




Nitric Oxide 

Pathway 

L-arginine 


type 5 

Nitric Oxide 

cGMP 

L-citrulline 

Prostacyclin 

Pathway 



Exogenous 

nitric oxide 

Vasodilation 






cAMP 

Vasodilation 



Endothelin Receptor Antagonists: 

Pivotal Trials 

Study Name 

Drug 

BREATHE-1 

Oral bosentan* 

vs placebo 

EARLY 

Oral bosentan 

vs placebo 

ARIES-1&2 

Oral ambrisentan § 

vs placebo 

N 

Etiology 

Class Design 

213 

PAH 

III, IV 

185 

PAH 

II 

394 

PAH 

II, III 

Double-blind 

16-week 

Double-blind 

6-month 

Double-blind 

12-week 

Positive 

Results 

•6MWD 

• Delay clinical worsening 

• Symptoms 


• Hemodynamics 

•6MWD 


*Bosentan = Tracleer ® . Approved for FC II-IV. 62.5-125 mg po bid. 

§ Ambrisentan = Letairis ® . Approved for FC II-III. 5-10 mg po qd 

Rubin L, et al. N Engl J Med. 2002;346:896-903. 

Channick RN, et al. Lancet. 2001;358:1119-1123. 

Galiè N, et al. Lancet, 2008;371:2093-2100. 

Galiè N, et al. Circulation. 2008;117:3010-3019. 

Prostacyclin 

derivatives 

15

120 

115 

110 

105 

100 

95 

90 

85 

80 

75 

70 

Is Treatment of Less Symptomatic 

(FC II) Patients Justified? 

% Baseline PVR at 

Month 6 

p

Study Name 

Drug 

SUPER-1 

Oral sildenafil* 

l b 

PDE-5 Inhibitor Pivotal Trials 

N 

Etiology 

Class Design 

278 Double-blind 

PAH 12-week 

I IV 

Positive Results 

vs placebo I-IV 

•6MWD 

• Symptoms 

• HHemodynamics d i 

PHIRST-1 

Oral tadalafil § 

vs placebo 

405 

PAH 

I-IV 

Galiè N, et al. N Engl J Med. 2005:353:2148-2157. 

Galiè N, et al. Circulation. 2009;119;2894-2903. 

Double-blind 

16-week 

*Sildenafil = Revatio ® . Approved for FC II-III. 20 mg po tid. 

§ Tadalafil = Adcirca ® . Approved for FC I-IV. 40 mg po qd. 

•6MWD 



• HRQoL 

PDE-5 Inhibitor Adverse Effects 

• Nose bleed 

• Headache 

• Dyspepsia 

• Flushing 

• Diarrhea 

• Visual changes 

• Contraindicated with use of nitrates 


Endothelin 

receptor A 


antagonists 

Approved Therapeutic Targets 

Endothelin 

Pathway 




Proendothelin 

Endothelin 

receptor B 




Nitric Oxide 

Pathway 

L-arginine 


type 5 

Nitric Oxide 

cGMP 

L-citrulline 

Prostacyclin 

Pathway 



Exogenous 

nitric oxide 

Vasodilation 






cAMP 

Vasodilation 



Prostacyclin 

derivatives 

17

Prostacyclin Analogues: 

Intravenous, Subcutaneous, or Inhaled 

Epoprostenol ( (Flolan Flolan ® 

or Veletri ® ) 

Treprostinil (Remodulin ® ) 

Treprostinil 

(Remodulin ® ) 

Iloprost 

Iloprost (Ventavis ® ) 

Treprostinil (Tyvaso ® ) 

Approved uses: Epoprostenol IV: FC III-IV, 2 ng/kg/min titrated to desired clinical response in 1-2 ng/kg/min 

increments. Treprostinil IV / SC: FC II-IV, 1.25-2.5 ng/kg/min/wk. IV=diluted. Inhaled: FC III, to 54 mcg, 4 inh/d. 

Iloprost Inhaled: FC III-IV, 2.5-5 mcg, 6-9 inh/d. 

Prostacyclin Analogues: Pivotal Trials 

Study Name / Drug 

AIR 

Inhaled iloprost vs placebo 

TRIUMPH 1 

Inhaled treprostinil vs 

placebo § 

SQ treprostinil 

vs SQ placebo 

TRUST 

IV treprostinil vs placebo 

IV epoprostenol 

vs conventional Rx 

IV epoprostenol 

vs conventional Rx 

N / Etiology / 

Class 

203 

PH 

III-IV 

Design Positive Results 

Double-blind 

12-week 

• Composite end point 

•6MWD 

• Symptoms 


235 

Double-blind •6MWD 

PAH 

12-week on 

III-IV* background oral Rx 

470 

Double-blind •6MWD 

PAH 

12-week • Symptoms 

II-IV 

• Hemodynamics y 

44 Double‐blind, placebo‐ • 6MWD 

PAH 

controlled • Symptoms 

III 

2‐week 

81 

Open-label •6MWD 

IPAH/FPAH 

12-week • Symptoms 

III,IV 


• Survival 

111 

Open-label •6MWD 

APAH SSc 

12-week • Hemodynamics 

III,IV 

• Symptoms 

*Approved for class III only. § Included background therapy with ERA or PDE5-I. 

Olschewski H, et al. N Engl J Med. 2002;347:322-329; Simonneau G, et al. Am J Respir Crit Care Med. 2002;165:800-804; 

Barst RJ, et al. N Engl J Med. 1996;334:296-301; McLaughlin VV, et al. Am J Respir Crit Care Med. 2008;177:A965. 

McLaughlin VV, et al. J Am Coll Cardiol. 2010;55:1915-1922. Badesch D, et al. Ann Intern Med 2000;132(6):425-432. 

Hiremath J, et al. J Heart Lung Transplant. 2010;29:137-149. 

IV Epoprostenol in IPAH: 

Change From Baseline in 6MWD 

Mediann 

change 

from baaseline 

(m) 

40 

30 

20 

10 

0 

‐10 

‐20 

‐30 

31 

Epoprostenol 

(n=41; baseline=315 m) 

p

IV Epoprostenol in PAH Due to Sclero-derma: 

Change From Baseline in 6MWD 

Median changge 

from 

baseline (m) 

80 

60 

40 

20 

0 

-20 

-40 

-60 

Badesch D, et al. Ann Intern Med. 2000;132:425-434. 

(%) 

100 

80 

60 

Conventional therapy 

(n=55) 

Epoprostenol (n=56) 

p=0.003 

Week 1 

p

On-therapy Favorable Prognostic 

Indicators 

• Functional class I or II 

• 6MWD >380 m 


– normal cardiac index (>2 2 L/min/m2 – normal cardiac index (>2.2 L/min/m ) 

– normal RA pressure 

• Positive response to CCB 

• BNP

70 

60 

50 

40 

30 

20 

10 

Inhaled Iloprost Added to Bosentan 

(STEP) 

0 

Mean 6MWD Change 

from Baseline (m) 

Bosentan 

+ Iloprost 

(n=32) 

p=0.051 0 051 

Bosentan 

+ Placebo 

(n=33) 

1.00 

0.75 

0.50 

0.25 

*log-rank test. 

McLaughlin VV, et al. Am J Respir Crit Care Med. 2006;174:1257-1263. 

Proportion Free of 

Clinical Worsening Iloprost 

Placebo 

p=0.02* 

0.00 

0 28 56 84 

Time (d) 

Inhaled Treprostinil Added to Bosentan or 

Sildenafil (TRIUMPH) 

Meters 

30 

25 

20 

15 

10 

5 

Change in Peak 6MWD 

by Specific Combination: 

6 

Background 

sildenafil 

Background 

bosentan 

Entire population 

22 

7 

6 

11 

25 

0 

Day 1 Week 6 

Time 

Week 12 

McLaughlin VV, et al. J Am Coll Cardiol. 2010;55:1915-1922. 

19 

9 

20 

Change from baselinee 

> defined value (meterss) 

% Achieving Specific 

6MWD Improvements 

Placebo 

Inhaled treprostinil 

50 

12 

31 

45 

14 

35 

40 

17 

37 

35 

22 

39 

30 

28 

43 

25 

32 

48 

20 

32 

52 

0 20 40 60 

Percentage of patients 

Combination Therapy Caveats 

• Experience evolving 

• Most data from ‘add-on’ - ? De novo? Order? 

• More drugs available 

– more options 

– more ways to get it wrong 

• More questions than answers 

• Costs/expenditures; third-party hurdles 

Taichman DB. Ann Intern Med. 2008;149:583-585. 

21

Antiproliferative Therapy in PAH 

• Abnormal endothelial and smooth muscle cell proliferation 

is a hallmark of PAH lesions 

• Endothelial cells in PAH are hyperproliferative, apoptosisresistant, 

and display abnormalities in cell cycle regulation 

• Plexogenic g lesions can have monoclonal origin g 

• Several experimental studies support this approach: 

– Statins 

– Tyrosine kinase inhibitors (e.g. imatinib) 

– SSRIs 

– DCA 

– Carbon monoxide 

• Humans studies are underway 

Imatinib in 

PAH 

Ghofrani HA, et al. Am J Respir Crit Care Med. 2010;182:1171-1177. 

Imatinib in 

PAH 

Ghofrani HA, et al. Am J Respir Crit Care Med. 2010;182:1171-1177. 

22

Conclusions 

• PAH therapy improves hemodynamics, 

functional capacity, morbidity and possibly 

mortality 

• Despite progress progress, PAH is still incurable and 

current therapies do not alter vascular 

remodeling characteristic of the disease 

• New therapies for PAH are needed 


Managing PAH 

Utilizing Treatment Algorithms 

in Practice 


(AQ-Cardiology) 




Pittsburg, PA 


Utilize evidence-based guidelines to select 

appropriate therapy to meet individualized 

patient treatment goals. 

23

CURRENT PRACTICE 

GUIDELINES 


Risk Assessment 

Risk Factor Lower Risk Higher Risk 

Evidence of RV failure No Yes 

Symptom progression Gradual Rapid 

Functional class II, III IV 

6-min walk distance >400 meters 10.4 

mL/kg/min 

Peak VO 2 20 mm Hg; CI

ESC/ERS 

Guidelines 

Galie N, et al. Eur Heart J. 2009;30:2493-2537. 

Pharmacotherapy Considerations 

• Most clinical experience in PAH trials with 

idiopathic disease or associated with connective 

tissue disease or anorexigen use 

• Limited long-term data 

• Limited experience with combination therapy 



PATTERNS 

25

REVEAL Registry: Summary of 

Treatments at Enrollment 

All Patients ERA PDE-5 Inhibitor Prostacyclin 

Overall 47% 49% 42% 

Monotherapy 18.5% 17.1% 12.1% 

Combo with 1 

oral therapy 

11.9% 11.9% 21.7% 

Combo with 1 

prostacyclin 

9.2% 12.5% 0.4% 

Combo with >1 

other therapy 

7.4% 7.5% 7.8% 

Badesch DB, et al. CHEST. 2010;137(2):376-387. 

REVEAL Registry: Summary of 

Treatments at Enrollment 

Class IV ERA PDE-5 Inhibitor Prostacyclin 

Overall 44.4% 49.2% 58.9% 

Monotherapy 4% 11.3% 19.3% 

Combo with 1 

oral therapy 

12 12.9% 9% 12 12.9% 9% 26 26.6% 6% 

Combo with 1 

prostacyclin 

14.5% 12.1% --- 

Combo with >1 

other therapy 

12.9% 12.9% 12.8% 

13% of patients were not treated with any PAH medication 

Badesch DB, et al. CHEST. 2010;137(2):376-387. 

Are Treatment Patterns the Same 

Throughout the US? 

Use of Any Continuous Prostanoid in WHO Class III/IV Patients, by Region 

Frantz, et al. Presented at the American Thoracic Society International Conference, San Diego, CA, May 15-20, 2009. 

26

FUTURE DIRECTIONS WHICH MAY 

IMPACT TREATMENT GUIDELINES 

Combination Therapies 

• Which medication is most effective and when? 

• “Front-loaded” vs. “step-wise” approach? 

• Does treating patients earlier make a difference? 

Rationale for a “Step-Wise Approach” 

• PAH is a progressive, insidious disease 

• Addition of new medications may be needed to 

achieve and maintain goals 

• Analogous to “CHF approach” 

27

Evidence for Combination Therapy in PAH 

Author Study 

Humbert M. 

Eur Resp J. 2004 

McLaughlin V. 

Am J Resp Crit Care 

Med. 2006 

Hoeper M. 

Eur Resp J. 2006 

Simonneau G. 

Ann Intern Med. 2008 

McLaughlin V. 

J Am Coll Cardiol. 

2010 

Tapson V. 

American Thoracic 

Society 2008 

RCT: randomized, controlled trial 

Background 

Rx 

Study Drug Design 

BREATHE-2 Epoprostenol Bosentan Up-front RCT 

STEP Bosentan Iloprost Sequential RCT 

COMBI Bosentan Iloprost 

Sequential open 

label 

PACES Epoprostenol Sildenafil Sequential RCT 

TRIUMPH 1 

FREEDOM C 

Sildenafil, 

bosentan, or both 

Sildenafil, ERA, 

or both 

Treprostinil 

(inhaled) 

Sequential RCT 

Treprostinil (oral) Sequential RCT 


Author Study Patients N 

Humbert M. 

Eur Resp J. 2004 BREATHE-2 

IPAH SSc 

SLE 

Duration 

(wks) 

I EP I EP TCW 

33 16 TPR - ND 

McLaughlin V. 

Am J Resp Crit 

Care Med. 2006 STEP PAH 67 12 6MWD - + 

Hoeper M. 

Eur Resp J. 2006 COMBI IPAH 40 12 6MWD - - 

Simonneau G. 

Ann Intern Med. 

2008 

McLaughlin V. 

J Am Coll Cardiol. 

2010 

PACES 

IPAH CTD, 

CHD 

267 16 6MWD + + 

TRIUMPH 1 PAH 235 12 6MWD + - 

Tapson V. 

FREEDOM C PAH 354 16 6MWD - - 

ATS 2008 

CHD, congenital heart disease; CTD, connective tissue disease; IEP, initial endpoint; IPAH, idiopathic PAH; ND, no 

significant difference; SLE, systemic lupus erythematosus; SSc, systemic sclerosis; TPR, total pulmonary 

resistance; TCW, time to clinical worsening 


• Exercise capacity (6MWD) the primary endpoint 

in all sequential studies 

• Only 2 of 6 met statistical significance for 6MWD 

and time to clinical worsening 

• Only 1 trial met significance for both endpoints 

Type of population and duration of disease? 

Need to re‐examine endpoints? 

Strategy – timing and type of therapy? 

‐ Is there a critical time to start new therapies that is being missed 

(eg, start with induction then add‐on therapies later?) 

28

Rationale for “Front-Loaded” Approach 

• PAH not always a “one drug” disease 

• Redundancy of pathways 

• Chemotherapeutic or induction approach 

AMBITION Trial 

A randomized, multicenter study of first-line 

AMBrisentan and Tadalafil combination 

therapy in subjects with pulmonary arterial 

hypertensION 

To compare 2 treatment strategies upfront 

combo (amb + tad) vs. mono (amb or tad) 

Event-driven trial 

Primary objective: time to clinical failure 

Secondary objectives: safety & tolerability, 

6MWD at peak and trough levels 

NCT01178073. http://www.clinicaltrials.gov/ct2/show/NCT01178073. Accessed Feb 2012. 

REVEAL Registry: Independent Predictors of 

Mortality Based on a Multivariate Model 

Parameter a Hazard ratio P value 

Connective tissue–associated PAH 1.59

REVEAL Registry: 

Risk Score 

• Composite Assessment of Risk 

• 19 easily obtained variables 

• 10 variables from 

demographics and exam 

• 9 from diagnostic tests 

• Useful at any point during therapy 

• Applicable for all PAH subgroups 

• Multivariable model coefficients were 

replaced with integer values to create 

calculator 

• Risk Calculator allows easy 

tabulation of risk score 

BNP, B-type natriuretic peptide; NYHA, New York Heart Association; REVEAL, Registry to Evaluate 

Early and Long-term PAH disease management; WHO, World Health Organization. 

Benza RL, et al. Chest. 2012;141:354-362. 

The Risk Score “Cliff-Effect” 

12-mo Kaplan-MMeier 

Survival, % 

100% 

90% 

80% 

70% 

60% 

50% 

40% 

30% 

20% 

10% 

0% 

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 

Predicted Risk Score 

Adapted from Benza R, et al. Circulation. 2010;122:164-172. 

Implications for Use of REVEAL Score 

• Incorporating score into therapeutic decisionmaking 

• Practical considerations: 

– Goal REVEAL score

Addressing gthe Challenges g in 

PAH Management 

Panel Discussion 

Transitions 

James C. Coons, PharmD, BCPS (AQ-Cardiology) 




Pittsburg, PA 

Transitions 

• Inhaled vs. parenteral prostacyclin therapy? 

• When is it acceptable to transition from 

p 

parenteral to inhaled therapy or vice-versa? 

31

Outpatient-to-Inpatient and 

Inpatient-to-Outpatient Transitions? 

Heather R. Bream-Rouwenhorst, PharmD, BCPS 



Clinical Pharmacy Specialist – Cardiology 

University of Iowa Hospitals and Clinics 

Iowa City, IA 

Dilemma 

Intravenous prostacyclin therapy is commonly 

ordered incorrectly. 

What steps should be taken to ensure smooth 

outpatient-to-inpatient and inpatient-tooutpatient 

transitions? 

Considerations 

• DOSING WEIGHT! 

• Patient may not “know” dose but MUST confirm 

– Knows number of vials needed to prepare 

cassettes 

– Dilutions 

– Often “mL per day” 

– Timing of next cassette/bag 

• Pump availability 

32


• Central vs. peripheral access 

– Concentration and stability issues 

– May need to convert cassettes to bags and viceversa 

• 4 mL/h lowest peripheral flow rate 

• Back-up 

– Essential for epoprostenol 

– Not needed for treprostinil 

Novel Therapies 

Coming Down the Pike 



Section of Pulmonary, Critical Care Medicine, Sleep and Allergy 

Institute for Personalized Respiratory Medicine 

University of Illinois at Chicago College of Medicine 

Chicago, IL 

Open Forum: 

Q and dAA 

33

Options in Action: A Case‐Based 

Approach to Pulmonary Hypertension 

Kimberly Ackerbauer, PharmD, BCPS 

Clinical Pharmacy Specialist, Cardiac Intensive Care Unit 

Rush University Medical Center 

September 13, 2012 

Objectives 

• Describe key elements to ensure safe and effective 

use of injectable agents to manage pulmonary 

hypertension 

• List steps involved in transitioning a patient from 

hospital p to home 

Additional Goals 

• Review differences between injectable prostacyclin 

therapies 

• Recognize potential complications associated with 

preparation and administration 

Pulmonary Hypertension 

• Pulmonary hypertension is a syndrome resulting in increased blood 

pressure in the pulmonary arteries which eventually leads to right sided 

heart failure 

• Hemodynamic definition: Mean pulmonary artery pressure >25mmHg 

with pulmonary capillary wedge pressure ≤15mmHg 

http://www.hwcrc.org/Health/Disease/circulatory%20system.htm 

Conflict of Interest 

• No conflicts of interest to disclose 

DW: Presents to Hospital 

• Chief Complaint: Shortness of breath and lower extremity edema x 2 days 

• History of Present Illness: DW is a 51 year old F with a past medical history significant 

for idiopathic pulmonary hypertension with symptoms of right heart failure. She presents to 

the ED with shortness of breath with minimal exertion and also notes lower extremity 

edema. She denies fever or other infectious symptoms. 

• Past Medical History: 

Idiopathic pulmonary hypertension 

Diabetes mellitus 

• Medications: 

–Metformin 1000mg BID 

–Sildenafil 20 mg q8h 

–Digoxin 125mcg daily 

–Furosemide 40mg daily 

WHO Classification 

I. Primary Pulmonary Arterial Hypertension 

• Idiopathic, familial, connective tissue disorders, HIV, portal 

hypertension, toxins, etc 

II. Associated with left heart disease 

III. Associated with lung g disease 

• COPD, interstitial lung disease, etc 

IV. Chronic thrombotic or embolic disease 

V. Miscellaneous 

• Sarcoidosis, compression of pulmonary vessels, etc 

8/29/2012 

1

Pulmonary Hypertension 

• Approximately 15% mortality within 1 yr on modern therapy 1 

• Predictors of a poor prognosis: 

• Advanced functional class (NYHA Functional classes) 

• Measured by 6‐minute walk test (20mmHg 

• Low cardiac index

Requirements for Safe Use: Physicians 

• Authorized Prescribers 

– Knowledge of disease state 

– Cost $100,000‐$160,000/year 

– Appropriate selection of agent 

– Administration challenges 

– Insurance approval process and requirements 

– Knowledge of side effects, monitoring parameters 

– Complications: 

• Infected lines 

• Transitioning between agents 

• Abrupt discontinuation 

Product Selection 3‐5 

Epoprostenol IV Treprostinil IV Treprostinil SQ 

Half‐life 6 mins 4 hours 4 hours 

Side effects 

ALL: Flushing, headache N/V/D, hypotension, dizziness, anxiety, arthralgia, jaw 

Specific Side 

Effects 

Stability Room Temp: 8hrs 

(Veletri 24h at RT) 

• Treprostinil 

pain, rash • , especially Half life with titration 

• Rate 

On ice: 24hrs • ICE 

• Infusion reaction 

Infection risk Infusion site pain 

48h, no ice 72h, no ice 

Cassette or 

Syringe change 

Q24h Q48h Q72h 

Tubing change Q72h Q72h Q72h 

Dilution Required Required None 

• Intravenous 

• Subcutaneous 

Treprostinil 

http://www.smiths-medical.com/ 

http://www.remodulin.com/hcp/iv‐administration.aspx 

Requirements for Safe Use: 

Technicians, Pharmacists, Nurses 

• Pharmacy technicians 

– Supply management 

– Preparation 

• Pharmacists 

– PPreparation, ti di dispensing i 

– Assist MDs, technicians, RNs in all responsibilities 

• Nurses 

– Assist MDs in all responsibilities 

– Administration 

– Pump management, monitoring 

Epoprostenol 

• Inpatient therapy 

– Hospital Pumps 

• Drug good for 48hr (okay to make back up) 

• 40hr in fridge + 8hr no ice needed 

– CADD pumps 

• Drug good for 48hr (okay to make back up) 

• 24hr in fridge then 24hr on ice 

• Home therapy 

• CADD pump 

http://www.smiths‐medical.com/ 

DW: Initiation of Therapy 

• Feb 24: Initiation of epoprostenol through PICC line 

– Dosing weight selected at 106kg 

– Started at 2ng/kg/min 

– Rush utilizes CADD pumps for all IV prostacyclin administration 

• Pharmacist 

– Verified indication (weight, dose, concentration) 

– Planned titration 

• Increase 24h dose by 30‐50% 

– Minimum flow rate for CADD ~40mL/24 (100mL cassette) 

• Specialty pharmacy recommendation to ensure accurate delivery of epoprostenol 

– Coordinate dispense times 

8/29/2012 

3

Example Cassette Calculations 

• Vial sizes: 0.5mg, 1.5mg (0.5mg=500,000ng) 

• Cassette volume 100mL 

• Pump programmed for mL/24h (round to nearest mL) 

• 0.5mg/mL into 100mL cassette=5,000ng/mL 

2ng/kg/min *106kg *60 min *24h =61 mL/24h 

5000ng/mL 

Enough for titration? 

61mL x 1.5 = 92mL (50% extra allows for titration) 

DW: Therapy Complications 

• Mar 7: ID service approves tunneled catheter 

• Changing lines: 

– “Bolus” or “IVP” dose 

• Duration of drug to get through new lumen 

• 48mL/24hr 48mL/24hr, lumen =4 4 mL=1.6hr mL 1 6hr for drug to get to circulation 

– Lumen volume 

• Attach syringe to line and withdraw until blood returns 

• Bolus dose is 60‐80% of lumen volume 

• 0.6 x 4mL = 2.4mL (same concentration) 

Transitioning to IV Treprostinil 

• Technique used (PICC line to tunneled catheter) 

– Bolus dose, lumen volume 

– Overlap epoprostenol and treprostinil x 15‐30min 

– 1:1 conversion, typically higher treprostinil requirements 

• Others (published reports) 

– IV Epoprostenol to IV Treprostinil 

• Rapid switch: change reservoir (same line used) 6 

• ↓ epoprostenol and ↑ treprostinil over 24‐48h (2 lines used) 7 

– IV Epoprostenol to SQ Treprostinil 

• Over 14 days (2 lines used) 8 

DW: Therapy Complications 

• Feb 25: Insurance paperwork started 

– Requirements (Medicare guidelines) 

– First time prescriber, difficultly identifying required 

paperwork without specialty pharmacy guidance 

• Mar 4: Patient develops E. Coli bacteremia, UTI 

– Antibiotics started, unable to culture PICC 

– Per ID service, bacteremia from UTI, unlikely line infection 

– Okay to use PICC until new line can be placed 

DW: Complications Continue 

• Mar 8: Informed coverage denied 

– Treprostinil preferred/approved 

• Mar 9: Transition to IV Treprostinil 

SQ Treprostinil 

• Pump programmed for mL/hr 

• Rate must be in increments of 0.002mL/hr 

• Vial sizes (multi‐dose): 1mg/mL, 2.5mg/mL, 5mg/mL, 10mg/mL 

• Concentration 1,000,000ng=1mg 

• 2.5mg/mL into 3mL syringe 

8ng/kg/min *106kg *60 min =0.02mL/hr 

2,500,000ng/mL 

• 0.02mL x 72h=1.5mL in syringe 

8/29/2012 

4

• Trained nurses 

– Programming rates 

– Alarms 

– Priming lines 

– Monitoring 

Administration/Nursing 

• Miscellaneous 

– Secondary means of IV access 

– Do not interrupt infusion 

– Do not FLUSH line, single lumen preferred 

– No other medications should be administered through the same line 

– Do not change dose based on daily weights 

Home Training 

• Training 

– Disease state 

– Mixing, documented mixing partner, aseptic technique, 

quiet area 

– Pump use, titrations, alarms 

– Drug and supply distribution 

– Extra supply 

– Signs and symptoms of too much/too little medication 

• When to call 

• Specialty RN determines when safe to go home 

• Mar 10: HOME!! 

Questions? 

Specialty Pharmacy Training 

• Training typically started prior to initiation 

• Safety screen/cleanliness 

– Patients generally not send to SNF 

• MMar 9 and d 10 10: specialty iltpharmacy h training t i i 

Home Therapy 

• Example: SQ treprostinil titration protocol 

• 63.6kg 

Dose ng/hr Conc (mg/mL) Rate Syringe volume (mL) 

15.5ng/kg/min g g 59,148 , 2.5 0.024mL/hr 1.8mL 

17ng/kg/min 64,872 2.5 0.026mL/hr 1.9mL 

18.5ng/kg/min 70,596 2.5 0.028mL/hr 2.1mL 

19.5ng/kg/min 74,412 2.5 0.030mL/hr 2.2mL 

21ng/kg/min 80,136 2.5 0.032mL/hr 2.4mL 

22ng/kg/min 83,952 2.5 0.034mL/hr 2.5mL 

23ng/kg/min 87,768 5 0.018mL/hr 1.3mL 



References 

1. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on 

pulmonary hypertension: a report of the American College of Cardiology Foundation Task 

Force on Expert Consensus Documents. J Am Coll Cardiol 2009;53:1573–619. 

2. Farber HW, Loscalzo J. Pulmonary Arterial Hypertension. N Engl J Med 2004; 351:1655‐65. 

3. Flolan [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2011. 

4. Remodulin [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2011. 

5 Veletri [package insert] South San Francisco CA : Actelion Pharmaceuticals US Inc 

5. Veletri [package insert]. South San Francisco, CA : Actelion Pharmaceuticals US Inc. 

6. Sitbon O, Manes A, Jais X, et al. Rapid switch from intravenous epoprostenol to intravenous 

treprostinil in patients with pulmonary arterial hypertension. J Cardiovasc Pharmacol. 2007 

Jan;49(1):1‐5. 

7. Gomberg‐Maitland M, Tapson VF, Benza RL. Transition from intravenous epoprostenol to 

intravenous treprostinil in pulmonary hypertension. Am J Respir Crit Care Med 2005; 

172:1586–89. 

8. Rubenfire M, McLaughlin VV, Allen RP, et al . Transition from IV epoprostenol to 

subcutaneous treprostinil in pulmonary arterial hypertension. Chest 2007; 132:757‐763 

8/29/2012 

5

Assessment Question 1 

Which of the following is NOT true regarding injectable 

epoprostenol? 

A. Half life ̃6mins 

B. Can be administered SQ 

C. Requires 24h cassette changes with the CADD pump. 


Which of the folloiwng are potential complications of IV 

treprostinil use? 

A. Infected lines 

B. Calculation errors 

C. Flushing the line it is infusing in 

D. All of the above 


Which of the following should NOT change throughout a 

patient’s course of therapy? 

A. Dosing weight 

B. Drug concentration 

C. Dose 

8/29/2012 

6

Presentation Outline 

ICHP Annual Meeting 

September 13-15- 2012 

“Evolving Trends That Will Impact Pharmacy’s Future” 

David A Zilz 

1) Introduction: Future leaders need a vision to meet future needs, expectations and 

mandates. 

a) Articulation critical issues 

b) Analyzing pertinent data and statistics 

c) Developing forecasting mentality 

d) Creating a vision on how to implement of patient and health-system services 

2) Critical Issues identified by ASHP Research and Education Foundation: 

a) Support the profession - advance pharmacy practice – foster leadership – 

accountability for patient outcomes 

b) Create demand – new models of practice – leverage expertise and unique 

abilities of pharmacists 

c) Drive advancement – technical, human and leadership competencies – in 

complex and rapidly changing organizations. 

d) Ensure financial stability of the Foundation 

3) Major dimensions in vision and forecasting: 

a) Patients and changing demographics 

b) Health care providers, especially pharmacists 

c) The restructuring of healthcare systems. 

d) Technology-Technicians-Trainees 

4) Patients and care statistics and trends: 

a) Numbers – patients 

b) Hospitals – beds – admissions – 

c) Emergency departments 

d) Disease trends 

5) Providers 

a) Physicians, hospitalists, nurses, physician assistants 

b) Pharmacists and the changing landscape 

c) Health systems and chain drug (health center) stores 

6) Future health systems and pharmacy enterprises 

a) Roles and responsibilities 

b) Leadership needed 

c) Future role of residency trained pharmacists 

7) Integrating career into a complete life plan 

8) Concluding remarks.

Illinois Council of Health‐Systems 

Pharmacists 

Annual Meeting 

Oak Brook, Illinois 

September 13‐15, 2012 

“Prayer to Owen Meany” 

• “Faith takes practice (not only in religious‐ 

but every aspect of life)” 

and 

• “We are always being trained for the next 

opportunity but we will not know why, until 

the moment we die.” 

Tomorrow and you!! ‐ 1 

ASHP’s Role in Strategic Leadership Development 

• Annual ASHP Conference for Leaders in Health‐System 

Pharmacy 

• Sections for Pharmacy Practice Manager and Clinical 

Specialists 

• Targeted monthly Newslinks 

• ASHP Connect 

• Specialized programming at ASHP national meetings 

• Educational and networking webinars 

• Web‐based practice resources 

• Residency accreditation 

Evolving Trends That Impact Will 

Pharmacy Practice in the Future 

David A. Zilz, B.S.Pharm., M.S, CDL, FASHP 

Senior Consultant, Corporate Pharmacy Programs 

University of Wisconsin Health Systems and Hospital & Clinics 

Clinical Professor Emeritus‐ UW School of Pharmacy 

Madison, Wisconsin 

The speaker has no conflict to disclose. 

Since Then‐Unique Path‐perhaps? 

• Practice 

• Associations 

• Consulting 

• Blue Collar 

• Volunteer 

Tomorrow and you!! ‐ 2 

ASHP Research and Education Foundation 

Visionary Leadership 

• Strategic Plan 

• approved (June 1, , 2011) 0 ) 

• identifies four critical issues 

• 12 strategic initiatives to address them. 

• That is truly “Visionary Leadership” 

8/29/2012 

1

The Critical Issue ‐ 1 

“Facilitate and strongly support the 

pharmacy p yp profession in advancing g 

pharmacy practice models that 

foster pharmacists’ leadership and 

accountability for patient 

outcomes.” 


“Drive the advancement of the 

technical, human, and leadership p 

competencies of pharmacists and 

pharmacy staff in complex and 

rapidly changing organizations.” 

The R & E Vision 

& Role of Forecasting 

Four major dynamics that will change your 

practices in the future: 

1) Patients and changing demographics 

2) Pharmacy & other health care providers 

3) Restructuring of the health care systems 

4) Technologies and Technicians + Students 


“Create demand for new models 

of pharmacy practice that 

leverage the expertise and 

unique abilities of pharmacists.” 


“Ensure the long‐term 

financial sustainability of the 

Foundation.” 

Statistics 

Patients 

8/29/2012 

2

Patient Activity ‐ 1 

Patients in U.S. 

– 310.9 million – 80+% will receive prescription 

– Beds available ‐ all facilities – 944,277 

– Community hospital/university – 805,593 

– Admissions annually all facilities – 37,479,709 – 

Discharges or 140,000 today‐most with new 

medications 

– Admissions in community/university – 35,527,377 

Patient Care Activities 

Emergency Room Patients 

• Injury‐related visits: 

� 42.4 million 

� 41.4 per 100 citizens (OH: 46.8; IL: 41.8; MA: 41.5; WI: 33.3; MI: 39.6; 

MD: 37.7; NC: 40.8) 

� All others discharged on medication 

• Patients seen by: 

� Physicians: 111,000,000 

� Physician Assistants and ER Techs: 21,450,000 

� Nurse Practitioner: 4,400,000 

� Patient patterns: 

� 4% of the patients account for 20% of all visits 

� 5% of patients account for 50+% of costs 

Diabetes –IAF Forecast ‐ 2 

We need to better forecast the profession’s future 

2010 to 2015 

• Major j complications: p visual, , renal, , amputations p 

– 3,676,300 to 4,850,900 = 1,052,500 + 28% 

• Over 65 –the percentages even greater. 

• “Point is” many entities are forecasting better 

each year 

Patient Care Activities 

Emergency Room Patients 

• ER visits: 

• 123.8 million (13‐17% admitted) 

• Medications: 

• 96,419,000 mentioned medications 

� 27,343,000 did not mention medications 

� ~30% had 3 or more medications 

� And 425,000 visits – inappropriate pain relieveres 

• Patients over 65 years of age: 

• 19,261,000 

� 1,675,000 with chest pain or shortness of breath 

Diabetes –IAF Forecast ‐ 1 

We need to better forecast the profession’s future 

2010 to 2015 

Population: p 310,233,000 , , to 325,540,000 , , = 

15,307,000 +4.9 % 

Pre‐diabetes: 79,016,000 to 82,915,000 = 

3,899,000 +5.0 % 

Diagnosed: 20,300,000 to 26,600,000 = 6,300,000 

+ 31% 

Statistics 

Providers 

8/29/2012 

3

Numbers Health Professionals 

Where do pharmacists fit? ‐ 1 

• Nurses –3.3+ million 

• Physicians – 980,000 

• Physician Assistants – 84,000 + 4,160/yr 

• Pharmacists – 270,000 

• Pharmacists –Health‐Systems ‐ 57,000 

– 5% retire each year – need 2,900 residency 

trained people every year just to replace retirees 

Physician Statistics 

• Total no. of physicians: 954,000 

� Resident positions: 110,000 (13% are non‐US citizens) 

• Primary Care: 352,908 

� Predicted to need 45,000 more by 2020 

� NNo. entering t i Family F il Medicine Mdii in i 5 years declined d li db by 25%; 25% reason 

for non‐physician providers 

• Medical school entering class: 18,000 

� In 2009, 4 new schools admitted 190 

� Pharmacy admits about 12,000 

Medical Residents & Students 

National Trends 

(April 2010) 

• Expansion of Medical Schools (as of Oct. 2009): 

� Number of students admitted: 18,000 

� Expanding di by b 340 3 0 

• Four new schools: 190 more students 

• Existing schools added 150 more students 

– Contrast 20++ new pharmacy schools 

• Residents‐in‐training in 2010: 

� 110,000 

� 14,300 non‐US citizens trained outside of US medical schools 

2011 AHA Futurescan 

• Clinical extenders will provide the bulk of primary care 

• Two Factors 

– Development of clinical guidelines 

– Pressing patient demands 

• Two‐thirds of responders believe by 2016 

– Advanced practice p nurses, , pphysician y assistants and 

pharmacists—will provide most primary care 

• Rationale for prediction: 

– 82% ‐ M.D.’s who oppose will reverse thoughts 

– Regulations in states will allow prescribing without M.D. signature 

– Potential for cost savings 

– 71% believe productivity and efficient use of resources will be same 

Physician Statistics 

• 60% of Health Systems own physician practices 

• 50% of all US physicians are employed by hospitals 

• 32% of first year residents have decided they would like to work 

for hospitals. 

• 75% of cardiology practices owned by Hospitals/Health 

Systems 

• Of the 10,400 certified Oncologists, McKesson Health 

Solutions employees 2,990 

Hospitalists 


• History of growth –Term was coined in 1997 and Society of 

Hospital Medicine was created 

• 1997 ‐‐‐ 1,000 

• 1999 ‐‐‐ 3,500 

2001 7 000 

• 2001 ‐‐‐ 7,000 

• 2003 ‐‐‐ 11,200 

• 2005 ‐‐‐ 16,400 

• 2007 ‐‐‐ 20,200 

• 2010 ‐‐‐ 30,000 + 

• 2015 ‐‐‐ ??,??? 

8/29/2012 

4

Hospitalists 


• January 2010 –Society of Hospital Medicine Members 

reached 10,000 

• Credentialing growth: 

– May 2009 – 500 inducted as “Fellows in Hospital Medicine 

• 2011 – – 119 New Fellows Approved 

– April 2010 –Senior Fellows Category Created 

• 2011 ‐ 59 

– April 2010 –Masters of Hospital Medicine 

• 2011 –4 

• Bottom line –outcomes and cost are now aligned by 

hospitals and physicians 

Nursing Profession Statistics 

• Nurses: 3.3+ million plus 2.2 million trained aids 

� Currently 2,618,700 listed positions (60% in hospitals) 

• Predict in 10 years, will need 581,500 additional RNs: The 

needs in practice settings beyond current staffing levels for 

nurses is projected to be: 

� Offices of physicians: 48% 

� Home health services: 33% 

� Nursing care facilities: 25% 

� Employment services: 24% 

� Hospitals (public and private): 17% 


• Advance Practice Nurses in 2008: 375,794 (28,369 doctorates) 

• In 2010, 153 schools granted 7,037 Doctor of Nursing Practice 

(DNP) degrees. In 2004, 4 schools granted 170 DNP degrees. 

• Nurse Practitioners’ growth in Master’s degrees: 

Ratio of Primary Care Physicians 

to Population 

• United States Average: 1.25 physicians per 1,000 population 

• Wi Wisconsin, i Mi Minnesota t ,and d Illi Illinois i are slightly li htl better btt off, ff 

with ratios between 1.21 to 1.5 

• Iowa and Indiana: Ratios between 1.0 to 1.2 


• Advance Practice Nurses in 2008: 375,794 

(28,369 doctorates) 

• Doctors of Nursing Practice 

– 2004: Four (4) schools ‐7 DNP degrees 

– 2006: Eight (8) schools‐74 DNPs degree 

– 2008: (92)Schools–361 DNPs = 3,415 enrolled 

– 2010: (153)Schools‐1,281 DNPs = 7,037 enrolled 

– 2011: (182) schools –1,581 DNPs = 8,973 enrolled 

– 2012: (101) more schools in planning stages 

• Additional PH.D. Enrollees 2011 – 4,907 


• Many Advanced Practice Nurses acting as 

physicians to fill primary care needs 

****I 2004 h A i A i i f 

• ****In 2004, the American Association of 

Colleges of Nursing mandated that by 2015, 

all entry‐level Advanced Practice Nurses 

(APNs), including NPs, attain a doctorate 

degree, Doctor of Nursing Practice (DNP) 

8/29/2012 

5

Numbers ‐ Health Professionals 

Where do pharmacists fit? ‐ 2 

How can 57,000 be organized within health‐ 

system pharmacy enterprises to collaborate 

with with 4.2 42million million M.D.s MDsand and R.N.s RNsto to optimize 

drug use for 310 million patients? 

Changing Pharmacy Landscape ‐ 1 

• Applicants to pharmacy schools 

– 115,000/year or more 

• Graduate from pharmacy schools 

– 12,000 annually and growing 

– Last two years plus all residents – 27,000 

additional pharmacy presence – educated – 

capable –with training and using good 

systems ‐ much better than what happens to 

patients histories and discharge now. 

– Plot ‐ Patient Benefit versus student 60%‐resident 30% ‐ preceptor 


• Residents 2010 –2,131 

• Residents 2011 – incomplete data 

– Predicting 2,300 

• Complete PGY2/Administration – 30 to 45 

– How about 50 to 500 in 5 years? 

– Increasingly with an “M” degree – M.S., M.P.H., M.B.A., Med, 

M.H.A., etc. 

• Needed to replace retirees: 

– 2,900 or 600 more / year than being prepared. 

Pharmacy Landscape 

• Applicants to pharmacy schools 

– 115,000+/year 

– From a pool of 3.2 million grads or 3.5% of 

graduates from 37,000 High Schools 

• 12,000 admitted 

– 0.375% of all high school graduates – REMEMBER ‐ 

there are 37, 000 valedictorians and 37,000 

salutatorians = 74,000 

– 1 of 3 valedictorians or 1 out of 6 combined 

valedictorians and salutatorians. 

– Academic excellence –very competitive era! 


• Residents 2010 

– Completed PGY1 ‐ 1,765 

– Completed PGY2 ‐ 366 

– Completed Total 2,131 

• PGY‐2 –So how unique are you? (12,000) 

l 

– Critical Care ‐ 85 

– Oncology –52 

– Ambulatory Care –49 

– Infectious Disease –35 

– Administration + M.S. –30 

– Psych and Internal Med –15 each 

• How will you uniquely provide “leadership” 


• Residents Forecast – 2012 

– Starting PGY1 2,027 

– Starting PGY2 438 

– Starting Total 2,465 

– ASHP Support Post‐match 20 

– Post Match Scramble ?? 

– Estimated Total Complete 

• Three year summary 

2,500 

– 2010 2,131 

– 2011 2,300 ‐‐ 7.9% increase 

– 2012 2,500 ‐‐ 8.7% increase 

– Total 6,831 ‐‐17.3% since 2010 

8/29/2012 

6

Pharmacy Landscape 

• PGY‐2: So how unique are you? 

100 

80 

85 

60 

40 

20 

52 49 

35 30 

15 15 

No. of PGY‐2 Residents 

0 by Specialty 

• How will Pharmacy uniquely provide medication management 

“leadership”? 


• 2020 ‐ Why you could easily become the “Greatest 

Generation of Pharmacists” 

• Merge “The Greatest Generation + That used to be 

us” + Generations: The History of America’s Future, 

1584 to 2069 ‐ “every 20‐25 years” 

– Large numbers 1964>2010 27,000 By 2020 at least 

another 27,000 

– Maturity & skills & multiple degrees 

– Tools‐data‐analytics‐multi‐media 

– Challenges & Opportunities very significant 

– Entitlements receding –> ^ competition > 

– ^ competence > ^ performance 

Walgreens – Numbers ‐ 2 

• 7,500 stores –1/3 open 24/7/365 ‐ 75% of US 

citizens within 5 miles –6 million customers a 

day –72 million different ones/yr . ‐‐ more 

than hospitals 

• 5.4 million flu vaccinations and 2 million H1N1 

vaccines plus infusion and respiratory home 

visits, Midwest $ Impact 

• Last two years ‐ opened 1 additional store per 

day –over 700 

• Blue Cross Blue Shield findings – 40% 

• Where do we fit and what is our connect, if any??? 


• Total residents completed program 

1964‐2010 ‐‐ 27,214!!!!! 

• If all practiced in health systems that 

would ld be b approximately i t l ½ of f current t 

practitioners 

• In 9 years another 27,000!!! 

– They will be part of greatest 

generation of pharmacists in history 

Walgreens – Numbers ‐ 1 

• Oh by the way – 5,300 students a year still 

receive Walgreens scholarships. 

• The “chains” will continue to be a major force 

in shaping our future practice models. 

Corporate Pharmacy‐competitors Pharmacy competitors or 

colleagues? 

• $67 billion in revenue 

• 70,000 health care providers (nurse practitioners, 

physicians assistants, home care nurses, physicians) 

AND 26,000 pharmacists 

Where do we fit with future 

practitioners??? 

• Annually –New patient care doctorates entering practice 

every year (based on 2010 data) 

• Medical Doctors ‐ 18,000 

• Pharm. D’s ‐ 12,000 

• Doctors of Nursing Practice 10 000+ 

• Doctors of Nursing Practice ‐ 10,000+ 

– Note ‐ nursing trend is exponential 

Total 40,000 

So what??? 

– Nearly 1/3 will be pharmacists! Where will they fit? 

– Who will collaborative practices be with??? 

– What should your contributions be??? 

8/29/2012 

7

What will you do as future 

practitioners by 2015??? 

At a minimum 

It had better include all the 

components components of the PPMI!! 

If not accomplished by then‐ 

your generation 

could be left behind 

Illinois Statistics‐1 

• Population: 12,814,300 

• Poverty Level: 2,455,700 

• Food stamps: 1,831,898 

• Uninsured: 1,863,800 

• Medicaid: 2,691,000 

• Medicare: 1,794,002 

• Obesity in Children: 35% 

• AIDS: 1,358 


• Physicians: 34,388 

– Male (65%) female (35%) 

– Lower percent of woman than other states 

– Perhaps a large number of old men physicians 

• Medical Students Graduating: 1,085 

– Male (50%) Female (50%) 

– 4 th largest number in nation behind –New York, 

Texas, Pennsylvania –More than Cal 

Kaiser Foundation 

www.statehealthfacts.org 


• Hospitals: 189 (20 For Profit) 

• Beds: 33,317 

• Admissions: 1,537,716 

– 120/1,000 Population (US‐114 & Wis‐103) 

– Medication History/discharged today: 4,271 

• Inpatient days: 7,534,808 

– Today 20,930 Ave LOS ?.? days 

• Emergency Room Visits: 3,656,201 

– 418/1,000 residents (high) WI is 380/1,000 

– Today will admit 10,156 (30 to 40%) ‐ all need a 

good med histories? 

Primary Care Physicians by Field, February 2012 

Ilinois 

Number 

Colorado 

% 

Internal Medicine 2,185 35% 158,116 41% 

Family 

Medicine/General 

Practice 

US 

# 

US 

% 

2,323 38% 113,516 30% 

Obstetrics/Gynec 

ology 708 11% 43,662 11% 

Pediatrics 968 16% 67,769 18% 

Total Primary 

Care 6,184 100% 383,063 100% 

8/29/2012 

8

Primary Care Physicians by Field, February 2012 

IL 

# 

IL 

% 

Internal Medicine 7,560 44% 158,116 41% 

Family 

Medicine/General 

Practice 

US 

# 

US 

% 

4,647 27% 113,516 30% 

Obstetrics/Gynecol 

ogy 1,985 12% 43,662 11% 

Pediatrics 2,909 17% 67,769 18% 

Total Primary Care 17,101 100% 383,063 100% 


• Nurses: 123,770 

– Nurse Practitioners: 4,539 

• Physician Assistants: 589 

• Dentists: 8,571 

– Male (72%) female (28%) 

• Pharmacists: ?????? 

Statistics ‐ Health Systems ‐ 1 

• Registered Hospitals – 5,795 

• Community Hospitals – 5,008 

– Not for profit – 2,918 

– For Profit – 998 

– State and local – 1,092 ‐ Universities are part 

– Urban – 3,011 

– Rural – 1,997 

– In a system – 2,921 

– In a network – 1,485 

Physicians by Specialty Area, February 2012 

IL 

# 

Anesthesiologists 1,830 10.6% 42,466 9.9% 

Emergency Medicine 1,858 10.7% 40,141 9.4% 

Oncology (Cancer) 568 3.3% 14,443 3.4% 

Psychiatry 1,759 10.2% 45,981 10.7% 

Surgery 11,760 760 10 10.2% 2% 43 43,579 579 10 10.2% 2% 

Endocrinology, Diabetes, 

& Metabolism 250 1.4% 5,956 1.4% 

IL 

% 

US 

# 

US 

% 

Cardiology 1,109 6.4% 26,701 6.2% 

All Other Specialities 8,153 47.2% 209,223 48.8% 

Total Specialty 17,287 100.0% 428,490 100.0 

Statistics 

Health Systems 


Rate of Integration: 

(2009‐1/week) 

(2010‐1/3 days) 

(2011‐1/2 ( / days) y) ‐ 

Therefore by 2013 there will likely be only 

2200 to 1,000 networks 

• Physician practices a key part 

• 60% of networks now own practices 

• 90 +% of cardiology practices owned by networks 

8/29/2012 

9


What are the seismic shifts that will impact 

you? 

1) Integration of physicians and office 

practices into the health systems. 

2) Seismic shift to “Ambulatory Care 

Awareness” in delivery of care! 

3) Optimum “expense management” plus 

“revenue enhancement” plus “revenue 

preservation” for the enterprise 

John David Mann’s 

“The Go‐Giver” 

"Our individual and collective potential has 

always been grossly underestimated... 

just as it is today. If you are alive and 

reasonably healthy today, it is virtually 

100% guaranteed that your potential has 

been, and is grossly underestimated." 

Future Pharmacy Enterprises ‐ 1 

• Must included at least the following 

considerations: 

– Developing sophisticated corporate structure 

– Financial impact pervasive – sophistication 

– Comprehensive drug policy development –key to future 

– CComplex, l intertwining i t t i i systems t – automation t ti and d computerization– t i ti 

better trained ‐ industrial engineered 

– Patients –increasing demand for continuum of care 

– Capable education and training, especially leadership 

• “Constructive INFLUENCE is everything” 

• Different leadership ‐ different training – The 

“M” factor MS,MPH,MHA,MBA, Medu,??? 

Health Systems and YOU!‐ 4 

A question for you future leaders of the 

profession –how as pharmacists do you best 

influence the “optimum use of medications in 

our society in collaboration ll b with h other h health h l h 

professions in the evolving “system” in which 

you practice? 

Pharmacy 

and 

Health Systems 

Future Pharmacy Enterprises ‐ 2 

• Must included at least the following 

considerations: 

– Patients –increasing demand for continuum of 

care 

– Capable education and training, especially 

leadership 

• “Constructive INFLUENCE is everything” 

• But perhaps different leadership ‐ different 

training 

8/29/2012 

10

Health Systems Pharmacy and TATAI 

“As we reengineer we will significantly improve 

efficiency overall and more important less 

pharmacist time related to product 

management” 

• TATAI 

– Technology 

– Automation 

– Technicians 

– Artificial Intelligence –Watson on Steroids 

• National Academy of Engineering Vision 

What is left for us to do? 

• As we reengineer the TATAI we will significantly 

improve efficiency and need less pharmacist 

time. Likely improvements every year for five 

years. 

• What is left for pharmacists? 

– Translation of evidenced base knowledge to 

patient outcomes thru “order sets” 

– Translation of medication information from and 

to patients in hospitals portals of entry and at 

discharge – “Communicate” 

The Future Pharmacy Mantra 

• For all Patients – “Instant Rapport” 

– Begin by recruiting into the profession those who 

are capable and interested in communicating with 

patients and then train them to a high level of 

sophistication 

– Buy into the concept “Every patient should know 

the name of their pharmacist!!!” 

• For pharmacy leadership and the C‐suite 

“Instant Executive Presence” – 

What training is needed? 

Patients –The Only Focus 

• Allen Flynn –U of Michigan: Informatist Perspective 

• With in 5 years –with TATAI ‐ Asked the question – 

”What will be left for pharmacists to do?” 

• Answer –Translation –at two levels 

– FFor a ffew – evidence id bbased dlleadership d hi iin 

“managing order set development and 

maintenance. 

– For many –translation of all facts so individual 

patients through direct encounters take them 

correct. 

“Leading the 

Way!!” 

What might your Visionary 

Leadership Role become? 

1) Predict how many of different patients by 

diseases 

2) Anticipate how to organize each of our 

rapidly consolidating systems pharmacy 

enterprises 

3) Identify how many PGY2 residency trained 

individuals we need 

4) Help ensure the long‐term financial 

sustainability of the Foundation 

8/29/2012 

11

“Visionary Leadership” 

• What society and patients really need 

• Articulating what future scenarios could look 

like –from “longer view” 

• Reality versus “wishful wishful thinking” thinking 

• Multiple inputs and multiple iterations 

AND 

• Based on short and long term trends 

• Bottom line – Think Forecasting 

“Pearls 2012” (2) 

• Volunteer for every possible project you can 

do well, it is the extra’s that will count. 

• During your interviews be able to “tell the 

stories” how you helped the department or 

hospital. Be totally honest and accurate 

• Learn how to “participate” in meetings!!! A 

“so what” list. What is your unique view? 

• Computers will not solve your problems, only 

quantify them. CIO –Large system 

“Pearls 2012” (4) 

• Quotes from residents completing their 

program: –what the youth are saying! 

–“Better to first roll up sleeves …. 

Delegate later”. 

–“Never “N ltfil let failure get t in i the th way of f progress, 

success and growth” 

–“Always, always remain positive and more 

importantly – open minded”. 

–“WOW” –the competition for positions is 

over powering. “Change in 3 years”‐DZ 

“Pearls 2012” (1) 

• Recognize “seismic” shifts when they occur – 

current ambulatory transitions! 

• Network –Network –Network –return 40 

years – better people passed between better 

networks during oversupply era. era 

• Starting during residency and first 5 years – 

become “content expert go to” person in some 

area. 

• Never forget the importance of professional 

and/or executive PRESENCE. 

“Pearls 2012” (3) 

• Quotes from residents completing their 

program –what the youth are saying!: 

–“Take advantage of every learning 

opportunity you have –it will serve you 

well, it is why residencies are so unique” 

–“Continually “C i ll work k on kknowing i yourself, lf so 

you can align what you do well with 

potential career successes”. 

–“Residency is “a sprint mode” and career is a 

marathon”. The “to‐do” lists get longer, the 

difference is, the buck now stops with you”. 

Learn to pace yourself. 

Always Remember John Maxwell 

• “Leadership is influence, nothing more and 

nothing less.” 

• “Leaders who last are marked by humility.” 

• “GREAT” leaders expect to pay a price.” 

• “GREAT” leaders set up their successor to be 

successful.” 

8/29/2012 

12

Readings 

The 21 Irrefutable Laws of Leadership 

John C. Maxwell 

The Tipping Point and Blink 

Malcolm Gladwell 

LeaderShock – How to Triumph over It 

Greg Hicks 

Managing and Leading: 44 Lessons Learned for 

Pharmacists 

Paul Bush and Stuart G. Walesh 

Common Question 

• Will I have a job? Deja Vu 1980 

• Recommendations: 

– Be able to tell a story on contributing to health‐ 

ssytem 

– Always network – it may be get your job 

y y g y j 

– In 5 years be health‐system, state or national 

“content expert. 

– Always volunteer to take on tasks –more the 

better right now 

– Seismic change toward ambulatory again 

– Salaries??? –11‐17% to 20% VVV 

“Thank you for 

letting g me spend p 

this day with you.” 

Most Important Reminder 

“Begin now to write a plan 

for life that will be fully 

integrated, holistic and 

satisfying!” 

See me later for more details!! 

Let us every day 

“Aspire to 

Inspire until 

we expire!” 

Post Test Questions 

1. How many new diabetic patients are expected to be 

diagnosed between 2010 and 2015? 

2. With the current rate of merger and acquisitions, How 

many health systems and/or networks are likely to be in 

existence by 2014. 

3. How many hospitals and acute hospital beds are in the 

St State t of f Illi Illinois? i ? 

4. Since 1997, when the term “hospitalist” was established, 

how many individuals are now part of that patient care giver 

category? 

5. Since the inception of the ASHP residency program (51 

years) , how many individuals have completed accredited 

residency programs and how many more will likely complete 

programs in the next 10 years? 

8/29/2012 

13

The State of the State: Do We 

Have All the PPMI Puzzle Pieces? 

Stan Kent, MS, FASHP 

Illinois Council of Health‐System Pharmacists’ Annual Meeting 


Objectives 

• Describe the current level of achievement of 

the ASHP Pharmacy Practice Model Initiative 

(PPMI) by Illinois hospitals. 

• Identify areas where Illinois hospitals exceed 

or fall short of the national average based on 

ASHP’s Hospital Self Assessment tool (HSA). 

• Discuss opportunities to improve the level of 

implementation of the PPMI within Illinois. 

Objectives for the Pharmacy 

Practice Model Initiative 

• Describe optimal pharmacy practice models 

that ensure safe, effective, efficient and 

accountable medication‐related care for 

patients patients. 

• Identify the most important patient‐care‐ 

related services 

• Foster understanding of and support for 

optimal pharmacy practice models by key 

groups 

• Nothing to disclose 

Disclosures 

GGoal: l 

Develop and disseminate a futuristic practice model 

that supports the effective use of pharmacists as 

direct patient care providers 

www.ashp.org/PPMI 

Objectives for the Pharmacy 

Practice Model Initiative 

• Identify existing and future technologies 

required to support optimal pharmacy 

practice models in health‐systems 

• Identify specific actions that pharmacists 

should take to implement optimal practice 

models 

• Determine the tools and resources need to 

implement optimal practice models 

8/30/2012 

1

What is a “Practice Model”? 

• Describes how pharmacy department 

resources are deployed to provide patient care 

services 

• Includes: 

� How pharmacists practice and provide care to patients; 

� How technicians are involved to support care; and 

� Use of automation/technology in the medication use 

system 

Why should we change? 

• Patients need help 

• We are not doing our best 

AJHP 2010;67:542 

Factors Driving Practice Change 

• US health care system faces challenges to 

improve health care quality and deliver 

cost‐effective service 

• Only half of patients receive the care they 

should 

• Physicians lack time/expertise 

• Projected primary care physician shortage ‐ 

pharmacists can help fill the gap 

AJHP 2010;67:1624‐1634 

Examples of Various Practice 

Models 

• Drug‐Distribution‐ 

Centered Model 

• Clinical Pharmacist‐ 

Segregated Model 

• Patient‐Centered 

Integrated Model 

AJHP. Woods, et al. 2011; 68: 259 

The education‐practice conundrum 

Clinical 

Focus 

Product 

Focus 

Pharmacy 

Education 

Time 

Pharmacy 

Practice 

Factors Driving Practice Change 

• Health care reform 

• Drug therapy is more complex and risky 

• Recognition of pharmacists among 

interdisciplinary peers as experts on drug 

therapy and medication‐use processes 

• Patients will be better served if pharmacists 

take control of their professional destiny 

AJHP 2009;66:713 

8/30/2012 

2

The PPMI –Three Components 

• Invitational Summit 

• Social Marketing 

Campaign 

• Raise awareness 

• Stimulate discussion 

• Disseminate the 

findings 

• Initiative Grants 

“The Summit” 

Nov. 7‐9, 2010 

• Two‐day invitational event ‐ approximately 

150 pharmacist participants 

• Plenary presentations and small work 

groups followed by a consensus process 

• Briefings published in Spring 2011 

The Hospital Self Assessment Tool 

• 106 questions assessing adoption of the 147 

beliefs, assumptions, and recommendations 

from the PPMI Summit 

• Hospital demographic data 

– medical and pharmacy residency programs, 

– hospital size and locations, and inpatient 

– pharmacists categorized to responsibilities/roles 

The Survey ‐ creating the framework… 

• Expert advisory committee 

• 180‐item survey distributed participants 

and the ASHP membership‐at‐large. 

• Questions Questions were categorized under: 

Overarching Principles 

Services 

Technology 

Technicians 

Implementing Change and Responding to Challenges 

After the Summit 

• 147 recommendations 

• Now what?......dissemination of results, 

measure over time 

• Hospital self assessment tool 

• State affiliate tool kit 

• National dashboard 

Development and Implementation 

Development 

• Wisconsin Administrative Residents 

• Summer 2011 testing 

Implementation 

• Available in October 2011 

• On ASHP PPMI webpage 

8/30/2012 

3

Completing the Self Assessment 

• http://www.ppmiassessment.org/ 

• Web‐based assessment 

• Anyone can complete, but an individual hospital 

can only l h have one “ffiil” “official” submission b i i 

• Use a team to fill it out to provide the most 

reliable data 

• Recommended to be filled out on a quarterly 

basis in order to measure progress 

Hospital Demographics 

Illinois National 

# hospitals reporting (as of 8/15/12) 26 679 

% with an “Action Plan” 42% 39% 

% Academic/University hospitals 20% 14% 

% Community hospitals 73% 54% 

Average bed size (range 25‐863; 7‐1728) 303 255 

%with a pharmacy residency 54% 41% 

% taking >6 pharmacy students/year 85% 68% 

Assessment Question #1 

How many Illinois hospitals have participated in 

the PPMI hospital self‐assessment? 

A. 26 

BB. 234 

C. 679 

Post‐Assessment 

• After completion the tool allows user to 

develop an “Action Plan” tailored to their own 

hospital/health system 

• Reports p can be produced p comparing p gindividual 

data to aggregated data 

• A list of resources will be provided to assist 

hospitals in implementing change in their 

institution 

Practice Model Demographics 

Clinical generalist ‐ limited differentiation 

of roles (“integrated”) 

Comprehensive – pharmacists in 

distributive distributive, integrated integrated, specialty roles 

Mostly distributive pharmacists with limited 

clinical services 

Separate clinical specialists and distributive 

pharmacists 

How we compare… 


35% 49% 

42% 31% 

19% 11% 

4% 9% 

• 106 items in assessment ‐ only compared 

items 10% better or worse than nation 

• Better in 11 items; worse in 4 

h d / i 

• Paraphrased some statements/questions 

• Some questions had multiple parts 

• Caveat: only 26 out of 234 hospitals in Illinois 

completed assessment 

8/30/2012 

4

Results –Where we are better….. 

Do pharmacy leaders regularly engage 

with administration about medication 

management systems? (B6a) 

Does lack of staff impede development of 

an optimal practice model? (B6b) 

Strategic plan for implementing 

technology and automation? (B6e) 


92% 81% 

54% 66% 

96% 81% 


Does hospital have a program with 

appropriate pharmacy involvement to 

achieve significant annual, documented 

improvement improvement in the safety of all steps in 

medication use? [B24e] 

Does the pharmacy department at your 

hospital routinely review hospital/health‐ 

system antibiotic resistance patterns? 

[B24l] 


88% 75% 

96% 85% 

Results –Where we are worse….. 


Pharmacists have a lead role in antimicrobial 

stewardship? (B23j) 

62% 79% 

Does hospital have processes to ensure 

medication‐related continuity of care? (B23l) 42% 54% 

Do pharmacists participate on your 

hospital's cardiopulmonary resuscitation 

teams? [B23o] 

Has your pharmacy department performed 

a proactive and ongoing risk assessment of 

medication‐use systems within the last 12 

months? [B17] 

42% 52% 

46% 60% 


Do hospital leaders strongly support 

models that maximize use of pharmacist 

roles? (B6h) 

Mechanism established to hold 

pharmacists accountable for actions and 

outcomes? (B7) 

Pharmacists involved in developing, 

reviewing, or approving new medication 

order sets? [B18] 


54% 43% 

58% 38% 

67% 53% 


Does the pharmacy department track and 

trend pharmacist interventions at your 

hospital? [B24m] 

Has the pharmacy p ydepartment p at your y 

hospital developed a plan to reallocate its 

resources to devote more pharmacist time to 

drug therapy management? (B24b) 

Do pharmacists have oversight and 

responsibility for medication distribution in 

all areas of your hospital that handle 

medications? [B25a] 



88% 76% 

67% 45% 

88% 63% 

In how many areas of the assessment are Illinois 

hospitals better than the national average? 

A. 4 

B 11 

B. 11 

C. 106 

8/30/2012 

5

Residency trained (B23p) 


All pharmacists 4% 9% 

Most pharmacists 33% 24% 

Some pharmacists 42% 42% 

None 21% 25% 

Medication Reconciliation (B23k) 


All patient care areas 13% 9% 

Some areas 25% 20% 

Partially performed 25% 27% 

None 37% 44% 

CPOE (C2b) 


All patient care areas 25% 32% 

Most areas 37% 26% 


None 17% 26% 

Board certification (B10) 


All pharmacists 0% 1% 

Most pharmacists 17% 11% 

Some pharmacists 33% 43% 

None 50% 45% 

Electronic Health Record (C2a) 





None 13% 10% 

BCMA (C2l) 





None 25% 35% 

8/30/2012 

6

Technician Distribution Tasks (D2) 

Are medication preparation and distribution tasks 

assigned to pharmacy technicians, to the extent 

possible, to allow redeployment of pharmacists' 

time to drug therapy management activities at 

your hospital? [D2] 


Tasks fully assigned all areas 25% 35% 

Tasks fully assigned some areas 46% 25% 

Partially assigned some/all areas 21% 35% 

Tasks not assigned 8% 5% 

Technician Supervision by 

Other Technicians 


Exists in all areas 25% 19% 

Exists in most areas 13% 15% 

Exists in some areas 0% 15% 

Does not exist 50% 43% 

Not applicable 12% 8% 

Next steps….. 

• Increase # of hospitals completing assessment 

• Use assessment for strategic planning 

• Suggestion: identify a PPMI lead at your hospital 

• More PPMI pearls sessions at ICHP meetings 

• More networking and sharing of ideas 

• Use students/residents to implement changes 

• Continue to improve; continue to measure 

Tech‐Check‐Tech (D3c) 

Is the accuracy of medication dispensing by 

technicians checked by other technicians who have 

appropriate education and training at your hospital? 


Ei Exists iin all ll areas 0% 4% 

Exists in most areas 0% 8% 

Exists in some areas 4% 8% 

Does not exist 33% 44% 

Not permitted by law 63% 36% 


In what areas can Illinois hospitals improve to 

advance practice? 

A. Hiring residency trained pharmacists 

BB. Tech Tech‐check‐tech check tech 

C. Antimicrobial stewardship 


It’s a marathon…. 

….not a sprint!! 

8/30/2012 

7

Solving the PPMI Puzzle ‐ 

Here Are Some Pearls 

Medication‐related Continuity of 

Care 

Justin Schneider, PharmD 

Sinai Health System 



Continuity of Care 

Definition [PPMI] 1 : 

Continuity of Care provides for the safe and seamless 

transition of patients within the health care 

continuum, such as when patients are discharged 

from an acute care setting to an outpatient 

community environment, and includes the 

communication of their medication list and 

treatment plan. 

PPMI Hospital Self‐Assessment 

When on rotations at your hospital, are pharmacy students 

trained on transitions of care in the medication‐use 

process? IL National 

62.50% 59.44% Yes 

20.83% 27.77% No 

16.67% 12.79% N/A 

Is medication reconciliation performed by the pharmacy 

staff at your hospital? 

IL National Medication reconciliation is . . . 

12.50% 9.05% Performed by pharmacy staff in ALL areas 

25.00% 19.81% Performed by pharmacy staff in SOME areas 

25.00% 26.83% Partially performed by pharmacy staff in some or all areas 

37.50% 43.68% Not performed by pharmacy staff 

0% 0.62% Not applicable 

Global Objectives 

• Describe individual components of the Pharmacy 

Practice Model Initiative (PPMI) where achievement 

in Illinois is less than optimal. 

• Provide recommendations for implementation of 

specific aspects of the PPMI including obtaining 

hospital administration buy‐in. 

• Discuss solutions to implementation of the PPMI in 

specifically identified areas. 


Do pharmacists facilitate medication‐related 

continuity of care when patients experience 

transitions of care? 2 

IL National 

4.17% 5.93% Exists in all areas/situations (100%) 

16.67% 22.00% Exists in most areas/situations (50‐99%) 

70.83% 53.04% Exists only in some areas/situations (1‐49%) 

8.33% 18.41% Does not exist (0%) 



Do pharmacists provide discharge education to patients at 

your hospital? 

IL National Discharge education is . . . 

0% 2.50% Provided to all patients 

25.00% 15.13% Provided to some patient‐care units 

20.83% 19.03% Provided to high‐risk patients 

54.17% 56.94% Available upon request 


Does your hospital have processes to ensure medication‐ 

related continuity of care for discharged patients? 

IL National 

41.67% 53.98% Yes 

58.33% 46.02% No 

8/29/2012 

1


Illinois vs. Nation 

Strengths: 

• Existence of at least some pharmacist‐facilitated medication 

reconciliation 

• Some discharge education provided by Pharmacists 

• Education of pharmacy students in transitions of care 

Opportunities: 

• Establish processes for medication‐related continuity of care 

for discharge patients 

• Expand reach of pharmacists’ role in transitions of care 

What opportunities are there 

ffor our profession? f i ? 

3 

Why are care transitions so 

iimportant? t t? 

Affordable Care Act 

• Value Based Purchasing 

• Readmission Reduction 

• Healthcare Acquired Conditions 

8/29/2012 

2

Overview of Value Based Purchasing 

Program 

• Improve quality and safety for Medicare beneficiaries by 

linking payment to quality of care 4 

• VBP Program is continuously updated as part of the 

annual rulemaking 

• Hospital performance for each measure is compared to 

national performance standards 5 

• Points awarded for: 

1.) Achieving high quality and 

2.) Improving towards goals 

6 

Value Based Purchasing Program: 

13 Clinical Process 

Measures: 45% 

•AMI ‐7a, AMI‐8a 

•HF‐1 

•PN‐3b, PN‐6 

• SCIP‐Inf‐1 SCIP Inf 1, SCIP‐Inf‐2 SCIP Inf 2, 

SCIP‐Inf‐3, SCIP‐Inf‐4, 

SCIP‐Inf‐9 

•SCIP‐Card‐2, SCIP‐VTE‐1, 

SCIP‐VTE‐2 

Proposed Federal Fiscal Year 2014 

8 HCAHPS 

Domains: 30% 

• Communication with 

Nurses 

• Communication with 

Doctors 

• Responsiveness of 

Hospital Staff 

• Pain Management 

• Communication About 

Medicines 

• Cleanliness and 

Quietness of Hospital 

Environment 

• Discharge Information 

• Overall Rating of 

Hospital 

3 Mortality 

Measures: 25% 

• AMI 30 day mortality 

• HF 30 day mortality 

• PN 30 day mortality 

The Readmission Issue 

• 19.6% of readmissions within 30 days and 

approximately 76% may be preventable 7 

• Over 50% of readmitted patients received no care or 

follow up in the 30 days after hospitalization 

• CMS estimates that unplanned readmissions cost 

Medicare over $17 billion annually 

6 

Value Based Purchasing Program: 

12 Clinical Process 

Measures: 70% 

• AMI ‐7a 7a, AMI‐8a AMI 8a 

•HF‐1 

•PN‐3b, PN‐6 

•SCIP‐Inf‐1, SCIP‐Inf‐2, SCIP‐Inf‐3, SCIP‐ 

Inf‐4 

•SCIP‐Card‐2, SCIP‐VTE‐1, SCIP‐VTE‐2 

Federal Fiscal Year 2013 

8 HCAHPS Domains: 

30% 

• Communication with Nurses 

• Communication with Doctors 

• Responsiveness of Hospital Staff 

• Pain Management 

• Communication About Medicines 

• Cleanliness and Quietness of Hospital 

Environment 

• Discharge Information 

• Overall Rating of Hospital 

Readmission Reduction 

Readmission Initiatives from Medicare and Medicaid 

– Improve quality of care and experience for patient 

– Trend to reduce or deny payments for preventable 

readmissions 

Most Common Reasons for 

Avoidable Admissions (AHRQ) 8 

• Poor discharge instruction 

• Poor transfer of information/handoff communication 

• Lack of timely post‐discharge physician visit 

• Poor medication reconciliation 

8/29/2012 

3

Readmissions Medicare: Hospital 

Readmissions Reduction Program 

Section 3025 of the Affordable Care Act 

• FY2012 –data collection/submission for 3 high‐volume conditions: HF, 

Pneumonia, AMI (2008‐2011) 

• FY2013—beginning Oct 1, 2012: CMS to reduce payments to 

hospitals with excess readmissions 

– Up to 1% reduction of net inpatient Medicare payment 

• FY2014—up to 2% payment reduction 

• FY2015—up to 3% payment reduction 

• Future—additional readmission measures? 

Readmissions: Medicaid 

• Providers to receive reduced (or zero) payment for potentially 

preventable readmissions 10 

• In process: Establishment of benchmarks for hospitals to measure and 

align payments to reduce hospital readmissions, inpatient 

complications, and unnecessary ER visits 

• Senate Bill 2840, p. 181‐2: ”The Department shall establish benchmarks for 

hospitals to measure and align payments to reduce potentially preventable hospital 

readmissions, inpatient complications, and unnecessary emergency room visits. In 

doing so, the Department shall consider items, including, but not limited to, historic and 

current acuity of care and historic and current trends in readmission. The Department 

shall publish provider‐specific historical readmission data and anticipated potentially 

preventable targets 60 days prior to the start of the program. In the instance of 

readmissions, the Department shall adopt policies and rates of reimbursement for 

services and other payments provided under this Code to ensure that, by June 30, 

2013, expenditures to hospitals are reduced by, at a minimum, 

$40,000,000.” 

Obtaining Hospital Administration 

Buy‐in 

PPMI: 

Do hospital leaders support (philosophically and with 

resources) pharmacy models that maximize use of 

pharmacist roles in patient care? 

IL National Leadership Support 

54.17% 43.21% Strong 

33.33% 47.27% Partial 

12.50% 8.74% Limited 

0% 0.78% None 

Readmissions Medicare: 

VBP Anticipated Rules 

• Anticipated rules that will penalize hospitals for 

“excess” 30‐day, all‐cause, unplanned readmissions 

• Proposed VBP Fiscal Year 2015 rules include the 

following readmission measures: 9 

– 30‐day Risk Standardized Readmission Measure: AMI, HF, 

PN, Total Hip/Total Knee Arthroplasty 

– Hospital‐Wide All‐Cause Unplanned Readmission (HWR) 

Healthcare Acquired Conditions 

• Trend from Medicare and Medicaid to reduce or 

deny payments for hospitalizations that include 

Healthcare Acquired Conditions (HACs) 

• Targeted Healthcare Acquired Conditions (HACs): 11 

– FForeign i object bj t retained ti dafter ft surgery 

– Air embolism 

– Blood incompatibility 

– Pressure Ulcer Stages 3 or 4 

– Falls and Trauma (includes: fracture dislocation, intracranial injury, crushing injury, burn, 

electric shock) 

– Vascular catheter associated infection 

– Catheter associated urinary tract infection 

– Manifestations of poor glycemic control 

Obtaining Hospital Administration 

Buy‐in 

Messaging 

• Value of pharmacists as medication expert 

• Relate to upcoming healthcare reform 

programs and d measures 

• Pharmacy profession’s role in the transitions 

of care 

It’s the right thing to do for our patients! 

8/29/2012 

4

Implementation of Medication‐ 

related Continuity of Care 

Services: 

Project RED, a Targeted Approach 

• Project RED 

– Re‐Engineered Hospital 

Discharge 

• AHRQ research grant14 : 

– Bi Brian JJack, k MD M.D., BBoston t 

University & Medical Center 

– Timothy Bickmore, Ph.D., 

Northeastern University 

Project RED 

• Purpose: 

– Re‐engineer the hospital 

workflow/process 

– Improve patient safety by 

using a discharge 

lead/advocate who utilizes 

specific, ifi reinforcing i f i action i 

steps 

• Improve the discharge 

process 

• Decrease hospital 

readmissions 

– Patient benefit 

• Clear after‐hospital care 

plan 

Project RED at Sinai Health System 

Joint Commission Resources 

• Heart Failure 

• Baseline Readmission rate = 16.47% 

• Pil Pilot t 

– Patients admitted with Primary 

Diagnosis of Heart Failure 

– Limitations: 

• English‐speaking patients 

• Opt‐in 

• Monday ‐ Friday 

• Members 

– Medical Staff 

– Nursing 

– Pharmacy 

– Social Work 

– Nutrition 

– Therapies 

– Senior Services 

– Disease Management 


• Mount Sinai Hospital 

– 319‐bed, major teaching hospital 

– Level I Trauma Center with ~60,000 

patients seen annually 

– Accredited Stroke & Chest Pain 

Center 

• Sinai Children’s Hospital 

– Level III NICU; Pediatric ICU 

– Pediatric trauma care, surgery & 

anesthesiology 

• Schwab Rehabilitation Hospital 

– 102‐bed, teaching hospital 

– Extensive inpatient & outpatient 

rehabilitation services and 

specialties: traumatic brain injury, 

stroke, spinal cord injury, sub‐acute 

care 

• Sinai Community Institute 

• Sinai Urban Health Institute 

Payer Mix 

Continuity of Care 

60% 

Medicaid 

20% 

Medicare 

15% Self Pay 

5% 

Commercial 

Insurance 

Definition [PPMI]: 

Continuity of Care provides for the safe and seamless 

transition of patients within the health care 

continuum, such as when patients are discharged 

from an acute care setting to an outpatient 

community environment, and includes the 

communication of their medication list and 

treatment plan. 

Timeline 

July 2010: 

July 2011: 

Joined Project 

RED 

February 2011: 

Pilot 

Program 

expansion 

8/29/2012 

5

Project RED process 

• Identification of Heart Failure Patients 

• Assessments by all involved Project RED Disciplines 

• Coaching/education of the patients throughout hospitalization 

• Assignment of Primary Care Physicians if a current relationship does not exist 

• Ongoing medication reconciliation 

• Arrangement of post‐hospitalization visits at a time convenient to the patient 

• Completion of the After Hospital Care Plan 

• Post discharge contact with the patient by Pharmacy and Disease Management 

– Knowledge and understanding of disease and personal care plan 

– Medication availability 

– Attendance at scheduled appointments 

– Admission to other hospitals or ED visits 

– Transportation or Home Health needs 

– Reinforcement of individualized care plan 

Transition from Inpatient to Home 

Prior to & at Discharge Post‐discharge 

•Review medication plan and recommend 

changes 

•Optimize medication therapy for specific 

disease state 

•Complete medication reconciliation 

•Provide medication education during 

hospital stay & at discharge 

•Contact patient after discharge (48‐72 

hours) 

•To reinforce understanding of medications 

•Identify Id tif availability il bilit of f medications di ti 

•Answer questions 

•Address any unmet needs 

•Interface with physicians, pharmacies 

•Continue patient follow‐up 

Challenges/Barriers –Real & 

Perceived 

• Program perception by patient 

– Intrusion on personal life 

– New method of bill collection 

• Phone calls post‐discharge 

– Timing 

– Phone number incorrect 

• Filling of Discharge/home medications 

– Patients uninsured 

– Medicaid Formulary 

• Other issues present: social, nutrition, transportation, housing 

TRANSITION from 

HOME to the 

INPATIENT Setting 

Medication Therapy Interventions 

INPATIENT SETTING 

TRANSITION from the 

INPATIENT Setting to 

HOME 

Medication History 

Ed Education ti – Ph Phase II 

Di Discharge h Process P 

POST POST-Discharge Di h 

Process 

-Medication 

-Medication List completed Patient Discussion 

-History 

-Medications in relation to by physician 

-48-72 hours 

-”Experience”: 

pathophysiology 

-Call for contact x 3 

*Adverse effects 

-Adverse event & symptom 

*Tolerance 

recognition 

*Compliance 

-Teach back 

-Call to pt’s pharmacy? 

-Evaluate for med-related 

causes of exacerbation 

-If appropriate, initiate 

EDUCATION – Phase I 

-Assess knowledge of 

disease & medications 

-Educate 

Pharmacotherapy – 

Inpatient Medication 

Optimization 

-Rx selection, dose, titration, 

goal 

-Adverse effects 

Medication 

Reconciliation 

-Reconciliation of home 

with inpatient medications 

Follow-up 

-Calls to other Health - 

Care providers 

Pharmacist Interventions 

Admissions Covered by Pharmacists 

Pilot 

Feb 2011 – Aug 

2011 

62 Admissions 

51 Patients 

Resident‐based 

Sep 2011 – Apr 

2012 

115 Admissions 

110 Patients 

Hybrid 

May 2012 –June 

2012 

32 Admissions 

27 Patients 

Medication History/Reconciliation 58 67 26 

Patient Education 42 63 27 

Medication Reconciliation at 

Discharge 

22 97 18 

Post Discharge Calls to Patient 38 98 29 

Pharmacotherapy Optimization of 

Inpatient Medication Regimen 

46 28 11 

Avg. # of Interventions per Patient 3.3 3.2 4.1 

Impact 

HF‐related 30 day related readmission rate 

– Same DRG with admission/readmission at MSH 

– Mean of 16.47% for the 11 month period prior to implementation 

– Dropped to an average of 9.55% post‐implementation 

► Decrease of 42% 

8/29/2012 

6

Question #1 

Within which programs are there opportunities 

for the pharmacy profession to provide 

medication‐related interventions and direct 

impact on patient care? 

AA. HHealthcare l h Acquired A i dC Conditions di i 

B. Value‐Based Purchasing 

C. Readmission Reduction 

D. Medicare 

E. Medicaid 

F. HCAHPS 

G. All of the Above 

Citations 

1. Pharmacy Practice Model Initiative, PPMI Hospital Self‐Assessment tool, 

AHSP. Available at: 

http://www.ppmiassessment.org/docs/assessment_questions.pdf. 

Accessed August 10, 2012. 

2. Pharmacy Practice Model Initiative, PPMI Hospital Self‐Assessment, Data 

Comparison Report. Accessed August 3, 2012. 

3. Williams, M. Care Transitions Conference, 07‐2012. Courtesy of Jeff 

Greenwald, MD, SFHM. Modified from Reason, J. BMJ 2000; 320 

4. Federal Register, Vol. 76, No. 230, p. 74535 and CMS website. 

5. CMS. Open Door Forum: Hospital VBP. July 27, 2011. Accessed from: 

http://www.cms.gov/Medicare/Quality‐Initiatives‐Patient‐Assessment‐ 

Instruments/hospital‐value‐based‐ 

purchasing/Downloads/HospVBP_ODF_072711.pdf. Accessed July 2, 

2012. 

Pharmacy 

– Pharmacist 

• Additional 1 FTE – Inpatient 

(July 2011) 

• Additional 0.5 FTE – Ambulatory 

Care (July 2012) 

– Resident 

• Longitudinal rotation (July 2011) 

– Student 

• Integrating into APPEs: 

– Hospital (2011) 

– General Medicine (2012) 

– Clinical Specialty (2012) 

– Future: 

• Technicians 

Program Expansion 

Question #2 

Ambulatory Care Staff 

Additional Targeted Diseases 

– Diabetes 

– COPD 

– AMI 

– Pneumonia 

For Federal FY2013, _____ of the total Value‐ 

Based Purchasing Calculation is related to 

HCAHPS domains? 

A. 45% 

BB. 30% 

C. 70% 

D. None of the above 

Citations (cont’d) 

6. Federal Register, Vol.77, No. 92, p. 28069‐70 and Vol. 76, No. 230, p. 

74544. 

7. Stephen F. Jencks, M.D., M.P.H., Mark V. Williams, M.D., and Eric A. 

Coleman, M.D., M.P.H. N Engl J Med 2009; 360:1418‐1428 

8. AHRQ. Reducing Avoidable Hospital Readmissions. Available at: 

http://www.ahrq.gov/news/kt/red/readmissionslides/readslides‐ 

contents.htm Accessed April 17, 2012. 

9. Federal Register, Vol. 77, No. 92, p. 28047‐8. 

10. Senate Bill 2840, Sec. 5‐5f. Elimination and limitations of medical 

assistance services. 

11. CMS. Hospital‐Acquired Conditions. Available at: 

http://www.cms.gov/Medicare/Medicare‐Fee‐for‐Service‐ 

Payment/HospitalAcqCond/Hospital‐Acquired_Conditions.html Accessed 

July 3, 2012. 

8/29/2012 

7

Citations (cont’d) 

12. AHRQ. Implementing Re‐Engineered Hospital Discharges. Available at: 

http://www.ahrq.gov/news/kt/red/redfaq.htm Accessed April 17, 2012. 

Questions? 

Justin Schneider, PharmD 

Director of Pharmacy 


Email: justin.schneider@sinai.org 

8/29/2012 

8

Solving the PPMI Puzzle‐ 

Here are Some Pearls 

Christine Yates, PharmD 

Clinical‐Staff Pharmacist 

St. Francis Hospital 

Litchfield, IL 

No conflicts of interest to declare 

Topics to Address 

• Medication related continuity of care 

providing for safe and seamless transitions 

• Other clinical services our department 

provides which reflect our commitment to 

PPMI 

Pharmacists 

• Accountability 

•Improve med use 

and outcomes 

• Enhance training 

What is PPMI? 

Technicians 

PPMI 

Technology 

Sources: 1 & 2 

Global Objectives 

• Describe individual components of the 

Pharmacy Practice Model Initiative (PPMI) 

where achievement in Illinois is less than 

optimal. 

• Provide recommendations for implementation 

of specific aspects of the PPMI including 

obtaining hospital administration buy‐in. 

• Discuss solutions to implementation of the 

PPMI in specifically identified areas. 

Poll the audience! 

How large (or small) is the hospital at which you 

primarily work? 

a) < 50 beds 

b) 50 50‐150 150 beds 

c) 151‐300 beds 

d) 301‐500 beds 

e) > 500 beds 

St. Francis Hospital 

Litchfield, IL 

• Catholic not‐for‐profit hospital established in 1875 

• 1 of 13 Hospital Sisters Health System (HSHS) hospitals 

throughout Illinois and Wisconsin 

• Admissions (FY 2011): 1,508 

ED Vi i (FY 2011) 11 936 

• ED Visits (FY 2011): 11,936 

• Pharmacy Requisitions (FY 2011): 187, 515 

• Critical access 

– Max of 24 patients 

– Average patient load = 14 

• High turn over rates 

• 1 pharmacist and 1 technician on duty each day Sources: 3 & 4 

8/29/2012 

1

A day in the life of a pharmacist at 

a critical assess hospital… 

• Daily interdisciplinary care rounds 

• Medication reconciliation within 24‐48 hours of admission 

• Discharge education/medication reconciliation 

• Core measures review 

• Daily anticoagulant and kinetics monitoring 

• Patient counseling—all warfarin patients, new medications 

• Antibiotic streamlining (cultures, IV to PO) 

• Renal adjustment of all medications 

• Pain score evaluations 

What? 

Why? 

Who? 

How? 

Medication Reconciliation 

Best possible medication list which is to be compared to 

medications ordered at all transitions of care. 

Joint commission requirement meant to reduce errors 

Study results vary, but over 50% of patients commonly have at least one 

error iin th the medical di l admission d i i hi history. t 

PharmD vs. MD: Home medications correctly recorded (p < 0.001) (Cornu 2012) 

MD: 891 (4 drugs per patient) 

PharmD: 1404 (7 drugs per patient) 

Patient/family interview, patient med list, pharmacy, previous 

admission/discharge records, nursing home records, PCP records, 

prescription bottles, etc. 

Sources: 6 - 10 

Have we made an impact? 

Number of changes made at St. Francis on Med Recs 

May 2012‐ mid August 2012 

15% 

7% 

3% 

50% 

25% 

None 

1 to 3 

4 to 6 

7 to 10 

10+ 

Interdisciplinary Care Rounds 

• Started rounding about 1.5 years ago to improve our HCAHPS scores 

• Members on the team: nurse manager, pharmacist, case management nurse 

• Our focus is to make sure the patient is getting the absolute best care 

Source: 5 

What do we do at St. Francis? 

• Conduct admission medication history 

services 

– Double check the “home” medication list 

– Clarify allergies/adverse reactions 

– Vaccine history if unclear 

– Medication education 

– Assess medication adherence 

• Nurse‐pharmacist collaboration 

Key Reminders 

• Time consuming process 

– High risk or ED admissions 

• Don’t forget the nursing home residents 

• Use several information sources 

• Be sure to involve the patient 

Be sure to involve the patient 

• Ask about vaccines and clarify allergies 

• Preparation 

– Bring the most recent list 

– Open ended questions 

– Match meds to disease states to find gaps in therapy 

– Ask specifically about multivitamins, OTC drugs, creams, eye drops, 

inhalers, herbal/supplements 


8/29/2012 

2

Discharge Education/Med Rec 

• Newest project (August 2012) 

• Discharge Team‐spearheaded by nursing 

• Discharge planning checklist and patient 

ffolder ld 

• Pharmacy’s current role 

– Be available for patient counseling and med 

education if questions are not answered by nurse 

– Can call patient at home 

Daily Anticoagulant and Kinetic Monitoring & 

Patient Counseling 

• Daily anticoagulant monitoring 

– Electronic “follow” 

– Worksheet with full details‐INR, bridging, interactions 

• Kinetics: ~ 95% of vancomycin and aminoglycosides ordered 

are managed by pharmacy 

• Counseling: 

– During rounds, med rec admission session, discharge, etc. 

– All warfarin patients 

• www.ahrq.gov/consumer/btpills.htm 

• highlights of medication 

– New medications 

Source: 12 

Renal adjustments for all drugs 

• We have a Pharmacy and Therapeutics 

committee approved policy that allows us to 

adjust all medications for renal function 

• Home medications: 

– Write a pharmacist to physician memo making them aware 

of the adjustment so that they can consider making the 

change permanent 

– Metformin‐electronic monitoring system facilitates Scr 

monitoring/possible reinitiating of therapy 

Core Measure Review 

• Created a binder with inclusion/exclusion and measure criteria 

• Data mining system helps “locate” the patients 

• Hospital generated reports (vaccine/pneumonia) 

• Admission reason on census list 

• Follow up with prescriber as needed. If not a time sensitive measure—leave a note 

in the chart. 

Pneumonia 

•Correct ABX 

within 24 hours 

•Appropriate 

ABX 

•Psuedomonas 

risk? 

•Excluded? 

Vaccinations 

•All patients 

need to be 

screened 

•Pneumococcal 

•influenza 

Stroke 

•tPA‐3hr window 

•VTE prophylaxis 

• Antithrombotic 

therapy 

•Statin 

• Anticoagulation (if 

cardioembolic) 

Heart Failure 

•ACE‐I/ARB 

Antibiotic streamlining 

Myocardial 

Infarction 

•Aspirin 

•ACE‐I/ARB if 

LVSD 

•Beta Blocker 

•Statin 


• Make sure you know who is on what 

antibiotics for which infection 

– Cultures? 

– Clinical improvement? 

– Does the drug appear appropriate per most likely 

bugs? 

– IV to PO? 

• Clinical electronic programs can help capture 

these patients 

Challenges 

• Gaining support (nursing, pharmacy, physician, 

administration) 

• Resistance to change 

• Understanding of the purpose behind the “pestering” 

• Gaining confidence to talk to patients, doctors, etc. 

• Knowledge deficits 

• Time constraints 

• Staffing issues 

• Flexibility 

Source: 13 

8/29/2012 

3

Goals 

• Continually evolving 

• Many more ideas 

– Specific disease state education 

– Enhance h education d i for f pharmacists/technicians 

h i / h i i 

• Room for improvement 

• Work on realistic and achievable goals— 

continue to enhance and add goals 

• Overcoming challenges 

Question 

What would be an appropriate way to overcome 

resistance to change on your quest to 

implement PPMI? 

AA. Educate nurses and physicians about your goals and the 

purpose behind the changes 

B. Wait another year or two before making adjustments 

C. Let pharmacy staff participate and take ownership in 

developing new PPMI processes 

D. Both A and C 

E. All of the above 

Case Question 

• JM, a 66 yof, was just admitted due to a fall which resulted in a broken 

shoulder. JM considers herself to be fairly familiar with her medications 

typically, however, she has been so busy entertaining an out of town 

family member, she has not had much free time. You are performing a 

medication history to obtain her current medication list. She tells you she 

just j recently y saw her PCP for high g blood pressure. p She knows that her 

doctor added a new medication that she takes twice daily, but she can’t 

remember what the drug name or dose is. What would likely be the 

quickest reliable source to find out this info? 

A. Get a hold of her physician’s office 

B. Call her pharmacy 

C. Look at the medication list which she brought in 

D. Interview her out of town family member 

E. Look at her previous hospital discharge medication list 

Bibliography 

1. Zellmer WA, ed. Proceedings of the Pharmacy Practice Model Summit: an invitational consensus conference conducted by ASHP and the ASHP 

Research and Education Foundation, November 7‐9, 2010, Dallas, Texas. Am J Health Syst. Pharm 2011;68:1077‐1160. 

2. PPMI. Pharmacy Practice Model Initiative and the PPMI National Dashboard. Available at 

www.ashpmedia.org/ppmi/docs/ppmi_national_dashboard.pdf. Accessed July 25, 2012. 

3. St. Francis Hospital. 2011 Annual Report. Available at www.stfrancis‐litchfield.org. Accessed July 31, 2012. 

4. Hospital Sisters Health System. 2011 HSHS Annual Report. Available at www.hshs.org/about_annual.aspx. Accessed July 31, 2012. 

5. Hospital Care Quality Information from the Consumer Perspective. HCAHPS. Available at www.hcahpsonline.org. Accessed August 4, 2012. 

6. Rabi SM, Padiyara RS. Pharmacist‐administered admission histories: focus on immunizations in medication reconciliation. Ann Pharmacother 

2008;42:728‐729. 

7. The Joint Commission: Core Measure Sets. Available at www.jointcommission.org/core_measure_sets.aspx. Accessed August 3, 2012. 

8. Cornu P, Steurbaut S, Leysen T, et al. Effect of medication reconciliation at hospital admission on medication discrepancies during hospitalization 

and at discharge for geriatric patients. Ann Pharmacother 2012;46:484‐94. 

9. Steurbaut S, Lies L, Lesen T, et al. Medication history reconciliation by clinical pharmacists in elderly inpatients admitted from home or a nursing 

home. Ann Pharmacother 2010;44:1596‐1603. 

10. Coffey M, Cornish P, Koonthanam T, et al. Implementation of admission medication reconciliation at two academic health sciences centres: 

challenges and success factors. Healthc Q 2009;12:102‐109. 

11. Karapinar‐Carkit F, Borgsteede S, Zoer J, et al. Effect of medication reconciliation with and without patient counseling on the number of 

pharmaceutical interventions among patients discharged from the hospital. Ann Pharmacother 2009;43:1001‐1010. 

12. US Department of Health & Human Services‐Agency for Healthcare Research and Quality. Available at www.ahrq.gov/consumer/btpills.htm. 


13. Zellmer WA. The future of health‐system pharmacy: opportunities and challenges in practice model change. Ann Pharmacother 2012;46(suppl 

1):S41‐5. 

8/29/2012 

4

Media‐Worthy Trials? 

Making Sense out of the Sensationalism 

Lara K. Ellinger, PharmD, BCPS 

Clinical Assistant Professor, Drug Information Group 

University of Illinois at Chicago 

I have no actual or potential conflicts of interest in relation to this program. 

Objectives 

• Describe the methods and key findings of the papers 

presented. 

• Explain how the WARFASA trial may affect venous 

thromboembolism (VTE) prevention strategies. 

• Summarize the findings and implications for practice of the 

trial that found an increase in cardiovascular death with 

azithromycin use. 

• Discuss the clinical significance of risk of stroke and 

myocardial infarction with use of hormonal contraception. 

• Compare and contrast 3 months of rifapentine and 

isoniazid with 9 months of isoniazid as treatment options 

for latent tuberculosis. 

Outline 

• Pertinent background 

• Study objective 

• Methods 

• Results 

• Critique/clinical implications 

8/30/2012 

1

Media‐Worthy Trial Assessment #1: 

ASPIRIN FOR PREVENTING THE 

RECURRENCE OF VENOUS 

THROMBOEMBOLISM (WARFASA 

TRIAL) 

N Engl J Med. 2012;366(21):1959-1967. 

Aspirin 

• Most commonly studied antiplatelet drug 

• Treatment and prevention of MI and stroke 

– ↓ vascular death by ~15% 

– ↓ nonfatal f lvascular l events by b ~30% 30% 

• Well‐known prevention What about of arterial events 

CHEST. 2012;141(2_suppl):e89S-e119S. 

venous events? 

8/30/2012 

2

Prevention of Recurrent VTE 

• Unprovoked at higher risk for recurrence than 

provoked 

• Unprovoked VTE 

– AAnticoagulation ti l ti for f 3 months th 

– Evaluate risk/benefit ratio after 3 months for 

extended anticoagulation 

CHEST. 2012;141(2_suppl):e419S-e494S. 

WARFASA 


– To assess the benefit of aspirin for prevention of 

recurrent VTE after completion of a course of 

vitamin K antagonists g (VKA) ( ) for unprovoked p VTE 

• Methods 

– Multicenter, randomized, placebo‐controlled, 

double‐blinded, event‐driven, approximate length 

2 years 

N Engl J Med. 2012;366(21):1959-1967. 

WARFASA 

• Interventions 

– Aspirin 100 mg once daily (n=205), placebo once 

daily (n=197) 

– Follow‐up every 3 months for 1 year then every 6 

months Inclusion Exclusion 

>18 years of age Known cancer 

N Engl J Med. 2012;366(21):1959-1967. 

First time diagnosis of 

unprovoked DVT, PE, or both 

Treated for 6‐18 months with 

vitamin K antagonist 

Known thrombophilia 

Indication for long‐term 

anticoagulation other than VTE 

Previous requirement for aspirin 

or antiplatelets 

Active bleeding, high risk, or 

bleed in past 6‐18 months 

8/30/2012 

3

WARFASA 

• Primary endpoint 

– Symptomatic, objectively confirmed recurrence of 

VTE (composite of DVT or nonfatal or fatal PE) 

• Secondary endpoints 

– Nonfatal MI, unstable angina, stroke, TIA, acute 

ischemia of lower limbs, death from any cause 

• Safety 

– Major bleeding 

N Engl J Med. 2012;366(21):1959-1967. 

WARFASA 

• Demographics 

– No significant differences between groups 

– Median age: 62 years 

– Approximately 2/3 male 

– 99% white 

– First event: approximately 60% DVT, 40% PE 

– Duration of VKA treatment 

• >50% took for 12 months 

N Engl J Med. 2012;366(21):1959-1967. 

WARFASA 

• Statistical analysis 

• Assumption of 40% RRR with aspirin 

• 8.0% expected event rate per year 

• 400 patients total to observe expected 

number of events 

• Estimated that 70 events would provide 

power of 80% to show superiority of aspirin 

over placebo 

N Engl J Med. 2012;366(21):1959-1967. 

8/30/2012 

4

VTE 

recurrence 

during 

study 

period 

VTE 

recurrence 

during 

study 

treatment 

WARFASA 

Primary Outcome: Recurrence of VTE within 2 years 

Aspirin (n=205) Placebo (n=197) 

28 43 

(6.6% per year) (11.2% per year) 

23 

(5.9% per year) 

N Engl J Med. 2012;366(21):1959-1967. 

39 

(11.0% per year) 

WARFASA 

HR with 

95% CI 

P‐value NNT 

HR, 0.58; 

95% CI CI, 

0.36 to 0.93 

PP=0.02 0 02 22 

HR, 0.55; 

95% CI, 

0.33 to 0.92 

P=0.02 20 

• Results –Post hoc 

– Patients with prior PE who had recurrence: 

• Aspirin: 6.7% per year 

• Placebo: 13.5% per year 

• HR, 0.38; 95% CI, 0.17 to 0.88; P=0.02 

– Patients with prior DVT who had recurrence: 

• Aspirin: 6.5% per year 

• Placebo: 10.2% per year 

• HR, 0.65; 95% CI, 0.65 to 1.20; P=0.17 

N Engl J Med. 2012;366(21):1959-1967. 

WARFASA 

• Results – Secondary 

– Death (any cause) 

• Aspirin: 6 patients (1.4% per year) 

• Placebo: 5 patients (1.3% per year) 

– Arterial events 

• Aspirin: 8 patients (including 2 MIs, 2 strokes) 

• Placebo: 5 patients (including 2 MIs, 1 stroke) 

– Major bleeding 

• 1 event in each group 

N Engl J Med. 2012;366(21):1959-1967. 

8/30/2012 

5

Aspirin Dose? 

• 81 mg aspirin may achieve same effects as 100 

mg aspirin 

• 300‐325 mg no different than 75‐100 mg for 

prevention of stroke stroke, MI MI, cardiovascular death 

(CURRENT‐OASIS 7) 

• Antiplatelet effect similar –dose‐dependent 

inhibition of prostacyclin 

N Engl J Med. 2010;363(10):930-942. 

Strengths 

• Well‐designed trial 

• Appropriate diagnostic 

criteria 

• Appropriate length 

N Engl J Med. 2012;366(21):1959-1967. 

WARFASA 

Limitations 

• Smaller study 

• Location/ethnicity 

• Compliance? p 

• Other medications taken 

concomitantly? 

• Vague descriptions for VTE 

risk factors 

• Majority treated with 

warfarin for 12 months 

WARFASA 

• Use of aspirin for unprovoked VTE may be in 

next CHEST guidelines 

• Related trials to keep a watchful eye for: 

– ASPIRE 

• Similar design to WARFASA 

• Inclusion: VKA for 3 months to < 12 months 

• Study length: median of 3 years 

– Analysis planned to combine results of WARFASA 

and ASPIRE 

N Engl J Med. 2012;366(21):1959-1967. 

8/30/2012 

6

Which patient might be a candidate for 

aspirin for prevention of recurrent VTE? 

A. Unprovoked VTE, 6 

month of VKA therapy, 

low bleed risk 

B. Unprovoked VTE, 3 

months of VKA therapy, 

low bleed risk 

C. Provoked VTE, 6 months 

of VKA therapy, low 

bleed risk 

D. Unprovoked VTE, 6 

months of VKA therapy, 

GI bleed 15 months ago 


AZITHROMYCIN AND THE RISK OF 

CARDIOVASCULAR DEATH 

N Engl J Med. 2012;366(20):1881-1889. 

Azithromycin 

• Background 

– Macrolide antibiotics have proarrhythmic 

potential 

• QT prolongation 

• Torsades de pointes 

• Sudden cardiac death 

– Up until recently, findings did not apply to 

azithromycin 

Clin Infect Dis. 2006;43(12):1603-1611. 

8/30/2012 

7

Azithromycin and CV Death 


– To determine the risk of cardiovascular death in 

patients taking azithromycin. 

• Methods 

– Retrospective, matched control, observational 

cohort study 

N Engl J Med. 2012;366(20):1881-1889. 


• Study cohort 

– Tennessee Medicaid population between 1992 

and 2006 

Inclusion Exclusion 

Prescribed azithromycin Serious illness 

No other abx filled same day as 

Rx benefits through Medicare 

azithromycin 

Not in hospital on day of 

Prolonged nursing home stays 

azithromycin Rx 

Ages 30‐74 years at Rx fill date 

Ongoing medical surveillance 

N Engl J Med. 2012;366(20):1881-1889. 


• Controls 

– Matched nonusers antibiotic‐free periods 

– Indication controlled for by patients who took 

other abx 

• Amoxicillin (primary control antibiotic) 

• Ciprofloxacin 

• Levofloxacin 

N Engl J Med. 2012;366(20):1881-1889. 

8/30/2012 

8


• Endpoint 

– CV death and death from any cause 

– Time frame of 5 and 10 days from date of Rx fill 

N Engl J Med. 2012;366(20):1881-1889. 


Study Group 

Baseline Characteristics 

Number of 

Prescriptions 

Primary Indication (%) 

Mean 

Summary CV 

Risk Score 

Azithromycin 347,795 Ear‐nose‐throat (42) 9.3 

Mthd Matched control t l– 

no antibiotic 

1,391,180 n/a 9.2 

Amoxicillin 1,348,672 Ear‐nose‐throat (51) 9.5 

Ciprofloxacin 264,626 Genitourinary (45) 10.3 

Levofloxacin 193,906 Ear‐nose‐throat (24) 10.6 

N Engl J Med. 2012;366(20):1881-1889. 



– Mostly female (77.5%) and white (~80%) 

– Mean age 49 years 

– Frequent use of CV or respiratory meds 

– In past 30 days from Rx fill 

• ~15% had ED visits 

• >1/4 had used abx 

– Most baseline characteristics in non‐azithro 

groups were P

Cumulative Incidence of Death (no./1 million courses) 

Among Patients Taking a 5‐Day Course of Azithromycin, 

Amoxicillin, or No Antibiotic 

No Antibiotic Amoxicillin Azithromycin 

HR, 2.88 

95% CI, 1.79-4.63 

P


Azithromycin Vs. Fluoroquinolones 

• Azithromycin increased risk for CV death 

compared to ciprofloxacin 

• HR HR, 3.49; 349 95% CI CI, 132t 1.32 to 926 9.26; P001 P=0.01 

• Azithromycin did not increase risk for CV 

death compared to levofloxacin 

• HR, 1.27; 95% CI, 0.66 to 2.47; P=0.48 

N Engl J Med. 2012;366(20):1881-1889. 


Overall Conclusion Patients should not stop taking 

• Azithromycin 

until 

resulted 

discussing 

in 

with 

small 

healthcare 

but significant 

professional. Prescribers should 

increase in risk for CV death 

be aware of the potential for QT 

– Increase greatest prolongation for those and found arrhythmias to be at highest 

CV risk with azithromycin. 

• 47 additional CV deaths per 1 million courses 

of azithromycin therapy when compared to 

amoxicillin 

• Also increased risk for overall death, but not 

non‐CV death 

N Engl J Med. 2012;366(20):1881-1889. 


Strengths 

• Large cohort observed over 

several years 

• 2 controls for confounders 

• Validity of study 

assumptions tested, with 

similar results 

N Engl J Med. 2012;366(20):1881-1889. 

Limitations 

• Observational, cannot 

observe cause and effect 

• Data from only 1 geographic 

location 

• Difficult to extrapolate to 

men, race other than white 

• Accuracy of 

database/coding 

8/30/2012 

11

Which of the following is true regarding 

azithromycin based on the recent trial in 

N Engl J Med? 

A. It can cause sudden CV 

death. 

B. It increases the risk for 

CV death compared to 

levofloxacin. 

C. It increases the risk for 

non‐CV death. 

D. It increases the risk for 

death from any cause 

compared to 

amoxicillin. 


THROMBOTIC STROKE AND 

MYOCARDIAL INFARCTION WITH 

HORMONAL CONTRACEPTION 

N Engl J Med. 2012;366(24):2257-2266. 

8/30/2012 

12

Hormonal Contraception and VTE 

• Attributed to 

– Estrogens 

• ethinyl estradiol 

• Induction of hepatic procoagulant proteins 

• Sex hormone‐binding globulins 

– Newer generation progestins 

• desogestrel, norgestimate, drospirenone 

• Effect on coagulation and fibrinolytic pathways 

• Resistance to activated protein C 

Pharmacists’ Letter/Prescriber’s Letter. August 2012: #280804. 

Hormonal Contraception and 

Thrombosis 

• FDA study (n=835,826) 

– Compared thrombosis rates between newer and older 

combined contraceptives 

– VTE risk increased with ring ring, patch patch, and drospirenone 

compared to older combined contraceptives 

• Denmark study ‐ VTE (n=1,626,158) 

– Compared VTE rates between nonoral users to nonusers 

– Risk increased with vaginal ring and transdermal patch 

BMJ. 2012;344:e2990. 

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdf. 

Stroke, MI, and 

Hormonal Contraception 


– To assess the risks of thrombotic stroke and MI 

associated with various types of hormonal 

contraception, p , according g to estrogen g dose, , 

progestin type, and route of administration. 

• Methods 

– Historical cohort study 

N Engl J Med. 2012;366(24):2257-2266. 

8/30/2012 

13



• Study cohort 

– Danish population from 1995 to 2009 

Inclusion (and Endpoint Inclusion) Exclusion (and Endpoint Exclusion) 

Diagnostic code of “transient 

Women 15 to 49 years y of age g 

iischemic h i attack” k” 

Diagnostic codes for “cerebral 

infarction” and “cerebral 

apoplexy” 

Prior diagnosis of venous or 

arterial thrombotic event 

Acute myocardial infarction Cancer (prior to study period) 

Gynecologic surgeries (some 

censored) 

Censored –pregnancy and 

coagulation disorders 

N Engl J Med. 2012;366(24):2257-2266. 



• Prescription/Lifestyle Data 

– Obtained from The Register of Medicinal Product 

Statistics 

– Categorized by: estrogen dose, dose progestin type, type 

route of administration 

– Duration of use: Rx fill date to last fill date/event 

– Rxs for DM, arrhythmia, HTN, hyperlipidemia 

– Smoking habits (from National Registry) 

N Engl J Med. 2012;366(24):2257-2266. 

http://laegemiddelstyrelsen.dk/en/topics/statistics,-prices-and-reimbursement/statistics-andanalyses/about-the-register-of-medicinal-product---tatistics-. 



• Endpoints 

– First‐ever thrombotic stroke and myocardial 

infarction 

N Engl J Med. 2012;366(24):2257-2266. 

8/30/2012 

14

• Age 

• Calendar year 

• Educational level 

• Type of contraception 

• Duration of use 

N Engl J Med. 2012;366(24):2257-2266. 

Variables 

• Predisposing risk factors 

– DM 

– HTN 

– Hyperlipidemia 

– Arrhythmia 

– Smoking 

Results: Overall Rates of Events 

1,626,158 women with 14,251,063 person‐years of observation 

Hormonal 

Contraception 

Status 

Thrombotic Stroke Myocardial Infarction 

Rates higher in 

nonusers due to older Number/ 

age and more risk person‐years 

factors compared to 

nonusers 

Crude incidence 

rates per 

100,000 person‐ 

years 

Number/ 

Person‐years 

Users 

Nonusers 

1051/4.9 

million 

2260/9.3 

million 

N Engl J Med. 2012;366(24):2257-2266. 

21.4 

24.2 

497/4.9 

million 

1228/9.3 

million 

Crude incidence 

rates per p 

100,000 person‐ 

years 

10.1 

13.2 

Does type of hormonal contraception affect 

rates of MI and stroke (according to this study)? 

8/30/2012 

15

Results 

All other things being equal… 

• Progestin‐only products did not significantly 

increase risk of stroke or MI 

– Th These include i l d IUD and d subcutaneous b t implants i l t 

• Risk of stroke was increased with vaginal ring 

(Adjusted RR=2.49; 95% CI, 1.41 to 4.41) but 

not patch 

N Engl J Med. 2012;366(24):2257-2266. 

Does type of progestin affect rates of MI and 

stroke (according to this study)? 

Results 

Progestins with lowest risk in combo 

with 30‐40 µg estrogen are of the 3rd All other things being equal… 

• No difference in rates among COCs generation containing 30 to 

40 µg ethinyl estradiol based on progestin type 

Combined Oral Contraceptives with 30‐40 30 40 µg Estrogen 

Event Risk Stroke, Adjusted RR (95% CI) MI, Adjusted RR (95% CI) 

Highest 

Lowest 

N Engl J Med. 2012;366(24):2257-2266. 

Desogestrel 2.20 (1.79‐2.69) 

Norethindrone 2.17 (1.49‐3.15) 

Norgestimate 1.52 (1.21‐1.91) 

Drospirenone 1.64 (1.24‐2.18) 

Norethindrone 2.28 (1.34‐3.87) 

Desogestrel 2.09 (1.54‐2.84) 

Norgestimate 1.33 (0.91‐1.94) 

Drospirenone 1.65 (1.03‐2.63) 

8/30/2012 

16

ARR=2.20, 2.28 for 

stroke, MI when in 

combo with 30‐40 µg 

estrogen 

Results 

Combined Oral Contraceptives with 20 µg Estrogen 

Progestin Type Stroke ARR (95% CI) 

ARR=1.64, 1.65 for 

MI 

stroke stroke, MI when in 

combo with 30‐40 µg 

estrogen 

Desogestrel 1.53 (1.26‐1.87) 1.55 (1.13‐2.13) 

Drospirenone 0.88 (0.22‐3.53) No MIs 

N Engl J Med. 2012;366(24):2257-2266. 

Results 

• No difference in risk between previous users 

and those who had never used hormonal 

contraception 

• Smoking was a risk factor factor, not a confounder 

N Engl J Med. 2012;366(24):2257-2266. 

Does estrogen dose affect rates of MI and 

stroke t k (according ( di tto this thi study)? 

t d )? 

8/30/2012 

17

Results 

Adjusted RRs for Events with COCs Based on Estrogen Dose 

N Engl J Med. 2012;366(24):2257-2266. 

50 µg: S, 1.97 and MI, 3.73 

30‐40 µg: S, 1.75 and MI, 1.88 

20 µg: S, 1.60 and MI, 1.40 



Strengths 

Limitations 

• Large amount of data • Study design 

• Valid Rx detail 

• Accuracy of 

• Sensitivity y analysis y 

database/coding 

performed • Some subgroups smaller 

• Danish population 



Overall Conclusion 

• Estrogen dose of 30‐40 µg combined with 

progestin correlated to a risk of arterial event 

13to 1.3 to 2.3 23times times higher than nonusers 

• Estrogen dose of 20 µg had risk of 0.9 to 1.7 

times higher than nonusers 

• Only small differences among progestins 

• Arterial events not as frequent as VTE with 

hormonal contraception 

8/30/2012 

18

Which of the following combinations 

had the highest rates of arterial 

events? 

A. Drospirenone + 

estrogen 20 µg 

B. Desogestrel g + 

estrogen 20 µg 

C. Norethindrone + 

estrogen 30‐40 µg 

D. Norgestimate + 

estrogen 30‐40 µg 


THREE MONTHS OF RIFAPENTINE 

AND ISONIAZID FOR LATENT 

TUBERCULOSIS INFECTION 

N Engl J Med. 2011;365(23):2155-2166. 

8/30/2012 

19

Treatment of Latent Tuberculosis (TB) 

MMWR Recomm Rep. 2003;52(RR-11):1-80. 

Treatment of Latent TB 

• INH treatment completion rates usually 30% 

to 64% 

• Efficacy important from public health 

standpoint 

• Concern for hepatotoxicity 

• 2002 RCT showed efficacy of weekly 

rifapentine and INH in continuation phase in 

patients with low bacterial burden 

Lancet. 2002;360(9332):528-534. 

3 Months of Treatment for Latent TB 

• Study Objective 

– To determine if a 3‐month course of weekly 

rifapentine and INH could be effective in treating 

latent M tuberculosis (TB) ( ) 

• Methods 

– Prospective, open‐label, randomized, multi‐center, 

noninferiority trial 


8/30/2012 

20


• Interventions 

– Combination therapy group (N=3986): 

• Rifapentine 900 mg + INH 15‐25 mg/kg (rounded to 

nearest 50 mg, max 900 mg) by mouth once weekly 

given under direct observation 

– Isoniazid‐only group (N=3745): 

• INH 5‐15 mg/kg (rounded to nearest 50 mg, max 300 

mg) by mouth daily self‐administered 

• Followed for 33 months 



Inclusion 

• High risk for progression from 

latent to active TB 

• Close contact of person with 

confirmed TB 

• Positive result on tuberculin 

skin test 

• HIV and positive tuberculin 

test, or negative if close 

contact 

• CXR consistent with previously 

untreated TB 


Exclusion 

• Confirmed TB 

• Resistance to INH or rifampin 

(in source case) 

• Tx with rifamycin or INH in 

past 2 years 

• Previous TB Tx 

• AST 5x ULN 

• HIV Tx within 90 days after 

enrollment 


• Primary endpoint 

– Culture‐confirmed TB in patients >18 years 

– Culture‐confirmed or clinical TB in patients


• Statistics 

– Expected event rate of 1.5% in INH group 

– Noninferiority margin set at 0.75% (upper limit) 

– 3200 subjects/group provide power of 80% to 

show noninferiority of combination group to 

isoniazid‐only group 




– Median age 35 

– 54% male 

– 57% white, 25% black 

– 89% from U.S. or Canada 

– 57% completed HS 

– 2% were HIV‐infection and very few had HBV, HCV 

– 50% had a history of EtOH use 

– >25% were current smokers 



• Overall, patients considered high‐risk 

• 322 ineligible: drug‐resistant or Cx‐negative 

source cases 

• Mean number b of f months h iin study d ~30 30 

• Completion of 33 months 

– Combination group: 88% 

– Isoniazid group: 86% 


8/30/2012 

22


Upper bound of CI is 


Overall conclusions 

• Rate of TB in combo group half of that in 

isoniazid alone group 

• Combo b therapy h x 3 months h may bbe 

treatment 

option for HIV‐negative patients with latent TB 

• Formal cost analysis 



Strengths 

• Similar findings when risk 

factors adjusted for 

• Large sample size 


Limitations 

• Open‐label study 

• Large noninferiority margin 

compared to incidence rate 

• Only applicable to countries 

with low and medium rates 

of TB incidence 

• Difficulty in capturing rare 

but serious AEs 

Latent TB Treatment Pros/Cons 

3 Months of Rifapentine + Isoniazid 9 Months of Isoniazid 

Pros Cons Pros Cons 

Shorter 

duration/greater 

compliance 

Possibly more cost‐ 

effective than 

isoniazid alone 

May be more 

effective in TB 

prevention than 

isoniazid alone 

Direct observation Current standard of 

care 

Lower compliance 

rates 

Not an option for Used in patients May be more costly 

patients with HIV with HIV than combination 

therapy 

May not be able to 

use in areas with 

high prevalence of 

TB 

Unknown resistance 

issues with 

rifapentine 

Used in areas with 

high prevalence of 

TB 

http://whqlibdoc.who.int/publications/2012/9789241503006_eng.pdf. 


May be less 

effective than 

combination 

regimen 

8/30/2012 

24

T/F: Rifapentine in combination with 

isoniazid had a greater rate of 

hepatotoxicity than did isoniazid alone. 

A. True 

B. False 

Questions? 

References 

• Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease. CHEST. 

2012;141(2_suppl):e419S‐e494S. 

• Eikelboom JW, Hirsh J, Spencer FA, Baglin TP, Weitz, JI. Antiplatelet drugs. CHEST. 

2012;141(2_suppl):e89S‐e119S. 

• Becattini C, Agnelli G, Schenone A, et al. Aspirin for preventing the recurrence of venous 

thromboembolism. N Engl J Med. 2012;366(21):1959‐1967. 

• Mehta SR , Bassand JP, Chrolavicius S et al; CURRENTOASIS 7 Investigators. Dose comparisons 

of clopidogreland aspirin in acute coronary syndromes. syndromes N Engl J Med .2010 2010 ;363(10): 930‐942 930 942 

• Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of 

cardiovascular death. N Engl J Med. 2012;366(20):1881‐1889. 

• Owens RC Jr, Nolin TD. Antimicrobial‐associated QT interval prolongation: pointes of interest. 

Clin Infect Dis. 2006;43(12):1603‐1611. 

• PL Detail‐Document. Hormonal contraceptives and the risk of thrombosis. Pharmacists’ 

Letter/Prescriber’s Letter. August 2012: #280804. 

8/30/2012 

25

References 

• Ouellet‐Hellstrom R, Graham DJ, Staffa JA, et al. Combined hormonal contraceptives (CHCs) 

and the risk of cardiovascular disease endpoints. October 22, 2011. 

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM277384.pdf. Accessed August 7, 

2012. 

• Lidegaard OM, Nielsen LH, Skovlund CW, Lokkegaard E. Venous thrombosis in users of non‐ 

oral hormonal contraception: follow‐up study, Denmark 2001‐10. BMJ. 2012;344:e2990. 

• Lidegaard g O, Lokkegaard g E, Jensen A, Skovlund CW, Keiding g N. Thrombotic stroke and 

myocardial infarction with hormonal contraception. N Engl J Med. 2012;366(24):2257‐2266. 

• Sundhedsstyrelsen: Danish Health and Medicines Authority. About the register of medicinal 

product statistics. Updated April 12, 2012. 

http://laegemiddelstyrelsen.dk/en/topics/statistics,‐prices‐and‐reimbursement/statistics‐ 

and‐analyses/about‐the‐register‐of‐medicinal‐product‐‐‐tatistics‐. Accessed August 7, 2012. 

• Sterling TR, Villarino E, Borisov AS, et al. Three months of rifapentine and isoniazid for latent 

tuberculosis infection. N Engl J Med. 2011;365(23):2155‐2166. 

• American Thoracic Society, CDC. Targeted tuberculin testing and treatment of latent 

tuberculosis infection. Am J Respir Crit Care Med. 2000;161:S221–S247. Available at 

http://www.cdc.gov/nchstp/tb/. 

References 

• Centers for Disease Control and Prevention. Treatment of tuberculosis: American Thoracic 

Society, CDC, and Infectious Diseases Society of America. MMWR Recomm Rep. 2003;52(RR‐ 

11):1‐80. 

• Benator D, Bhattacharya M, Bozeman L, et al. Rifapentine and isoniazid once a week versus 

rifampicin and isoniazid twice a week for treatment of drug‐susceptible pulmonary 

tuberculosis in HIV‐negative patients: a randomized clinical trial. Lancet. 2002;360(9332):528‐ 

534. 

• Supplementary appendix to Three months of rifapentine and isoniazid for latent tuberculosis 

infection. 

http://www.nejm.org/doi/suppl/10.1056/NEJMoa1104875/suppl_file/nejmoa1104875_appe 

ndix.pdf. Accessed August 10, 2012. 

• The World Health Organization. WHO policy on collaborative TB/HIV activities. 

http://whqlibdoc.who.int/publications/2012/9789241503006_eng.pdf. Accessed August 13, 

2012. 

1. Which of the following is TRUE regarding 

noninferiority trials? 

a. The standard of care is used as the active 

control control. 

b. Superiority cannot be assessed. 

c. Placebo is used as the control. 

d. Achieving noninferiority means the comparison 

is the same as the active control 

8/30/2012 

26

2. Which of the following statements is a reasonable conclusion from the 

WARFASA trial? 

a. Aspirin 325 mg daily is an effective regimen for further prevention of 

unprovoked venous thromboembolism after warfarin treatment is 

completed. 

b. The risk of bleeding outweighs the benefits of prevention of venous 

thromboembolism with aspirin. 

c. A low dose of aspirin for further prevention may be considered in 

patients with unprovoked venous thromboembolism who have 

completed warfarin treatment. 

d. The WARFASA trial showed a decrease in venous thromboembolism, 

myocardial infarction, and stroke in patients with unprovoked venous 

thromboembolism who were treated with aspirin, as compared to 

placebo, after warfarin therapy was completed. 

3. True/false. Combination therapy of 

rifapentine with isoniazid was effective 

treatment of latent TB in patients who were 

co‐infected co infected with HIV. HIV 

a. True 

b. False 

4. True/false. In combination oral 

contraceptives, the type of progestin 

correlated to a difference in arterial event risk 

when used in combination with 20 µg 

estrogen, but not when used in combination 

with 30‐40 µg estrogen. 

a. True 

b. False 

8/30/2012 

27

5. Which of the following is true regarding azithromycin 

and the risk of sudden cardiac death? 

a. The results of the study warrant routine cardiac 

monitoring for patients taking azithromycin. 

b. The risk of death from any cause is increased 

with azithromycin as compared to amoxicillin. 

c. The risk of cardiovascular death is increased with 

azithromycin as compared to levofloxacin. 

d. The Food and Drug Administration recommends 

prescribers to avoid prescribing azithromycin in 

patients with risk factors for sudden cardiac 

death. 

8/30/2012 

28

Fitting the Counseling Piece into 

Medication Reconciliation 

Carrie i Vogler, l Pharm.D., h BCPS 

SIUE School of Pharmacy, Edwardsville, IL 

Kristine Gleason, RPh, MPH 

Northwestern Memorial Hospital, Chicago, IL 

Objectives 

• Explore the importance of medication 

reconciliation in the health care system 

• Evaluate different medication reconciliation 

models or programs 

• Identify the barriers involved in successful 

patient counseling 

• Describe and demonstrate different interview 

techniques used to improve patient counseling 

Which of the statements best 

describes when you perform 

patient counseling? 

A. I counsel all patients who have 

medication changes 

B. I only counsel patients when 

consulted co su ted by a pphysician ysca oor nurse use 

C. I counsel patients only on specific 

high risk medications such as 

warfarin 

D. I rarely counsel patients due to 

the pharmacy’s location (e.g., 

basement), time, resources, or 

other reasons 

25 

Conflict of Interest Statement 

• Carrie Vogler has no conflicts of interest to 

disclose. 

• Kristine Gleason serves as a consultant for the 

Health Research and Educational Trust’s Trust s 

(HRET) contract from the Agency for 

Healthcare Research and Quality (AHRQ) 

"State‐Based Patient Safety Learning Network" 

(Contract HHSA290200900014C) 

How would you describe your 

facility? 

A. Community or Outpatient 

Pharmacy 

B. Hospital with 500 beds 

E. Other practice site 

How familiar are you with the 

BOOST and MATCH programs? 

A. I use either the BOOST or 

MATCH process at my 

institution 

B. I am familiar with the 

programs but my institution 

does not use them 

C. I have heard of the programs 

but I do not know what they 

are 

D. I have never heard of these 

programs 

8/29/2012 

20 

25 

1

Why Focus on Medication Reconciliation? 

Statistics on U.S. Prescription Drugs 

• Per 2005‐2008 data, the question “In the past 

month, percent of persons using at least X 

prescription drug (s)” revealed: 

• One prescription drug: 47.9% 

• Three or more prescription drugs: 21.4% 

• Five or more prescription drugs: 10.5% 

• Per 2008 data, data the table below provides 

statistics stratified by type of medical visit: 

Types of Medical Visits 

Number of Drugs 

Ordered or Provided 

Percent of Visits 

Involving Drug Therapy 

Physician Office Visits 2.3 billion 74% 

Hospital Outpatient Department Visits 280.1 million 76% 

Hospital Emergency Department Visits 238.3 million 78% 

Source: Centers for Disease Control and Prevention. FastStats. Available at http://www.cdc.gov/nchs/fastats/drugs.htm. 

Accessed 7/19/2012. 

Medication Reconciliation Facts 

• Approximately 1.5 million preventable adverse 

drug events (ADEs) occur annually due to 

medication errors, at a cost of $3 billion per year. 

• ADEs account for 2.5% of estimated emergency 

department visits for all unintentional injuries 

and 6.7% of those leading to hospitalization. 

Source: Preventing Medication Errors: Quality Chasm Series (2007). Committee on Identifying and Preventing 

Medication Errors, Philip Aspden, Julie Wolcott, J. Lyle Bootman, Linda R. Cronenwett, Editors. 

Budnitz DS, Pollock DA, Weidenbach KN, et al. National surveillance of emergency department visits for 

outpatient adverse drug events. JAMA .2006;296(15):1858‐66. 

Pharmacist Impact on Medication Reconciliation 

• 36% of patients had medication errors at admission, 

of which 85% originated from the patient’s 

medication history 

• Pharmacist shown to reduce physician visits, ED visits, 

decrease hospital days, and overall health care costs 

• Med rec reduced discharge medication errors from 

90% to 47% on a surgical unit and from 57% to 33% 

on a medical unit of a large academic medical center 

Source: Gleason KM et al. Results of the MATCH study: an analysis of medication reconciliation errors and risk factors at 

hospital admission. J Gen Intern Med. 2010 May;25(5):441‐7. 

Improving Care Transitions: Optimizing Medication Reconciliation. American Pharmacist Association and American 

Society of Health‐System Pharmacists. March 2012. Accessed 8/12/12/ at: 

http://www.ashp.org/DocLibrary/Policy/PatientSafety/Optimizing‐Med‐Reconciliation.aspx 

The Joint Commission 

Medication reconciliation consists of 5 steps: 

1. Develop a list of current medications 

2. Develop a list of medications to be prescribed 

3. 3 Compare Co pa e tthe emedications ed cat o s on o the t et two olists sts 

4. Make clinical decisions based on the comparison 

5. Communicate the new list to appropriate 

caregivers and to the patient 

Source: The Joint Commission. Hospital: 2012 National Patient Safety Goals. Available at: 

http://www.jointcommission.org/standards_information/npsgs.aspx. Accessed 8/13/2012 

Avoiding Readmissions: 

Preventable ADEs After Hospital Discharge 

• 400 consecutive hospitalized general medicine patients 

discharged home 

– 19% of patients had an adverse event (AE) within 3 weeks of discharge 

– 66% of AEs were adverse drug events (ADE) 

– Most ADEs were preventable or ameliorable 

• System modifications recommended by authors: 

– Evaluate patients at discharge to identify unresolved problems 

– Educate patients about drug therapies, side effects, and what to do if 

new or worsening signs/symptoms 

– Improve monitoring of therapies and patients’ overall condition 

Source: Forster et al. The Incidence and Severity of Adverse Events Affecting Patients after Discharge from the 

Hospital. Ann Intern Med. 2003;138:161‐167. 

Barriers to Medication Reconciliation 

and Patient Counseling 

• Time 

• Incomplete, non‐standardized medication lists 

• Insufficient communication among health care 

professionals f i l 

• Lack of established best practices 

• Health Literacy, cognitive status or non‐English 

speaking patients 

Source: Improving Care Transitions: Optimizing Medication Reconciliation. American Pharmacist Association and 

American Society of Health‐System Pharmacists. March 2012. Accessed 8/12/12/ at: 

http://www.ashp.org/DocLibrary/Policy/PatientSafety/Optimizing‐Med‐Reconciliation.aspx 

8/29/2012 

2

Current Evidence: 

Implementing Bundled Interventions 

Pre‐Discharge 

Intervention 

• Patient education 

• Med Rec 

• Discharge g planning p g 

•Scheduling follow‐up 

appointment 

Source: Hansen et al. Interventions to Reduce 30‐Day 

Rehospitalization: A Systematic Review. Ann Intern Med. 18 

October 2011;155(8):520‐528. 

Bridging 

Interventions 

Post‐Discharge 

Intervention 

• Transition coaches • Follow‐up telephone calls 

• Continuity across • Patient‐activated hotlines 

settings g 

• Timely y communication 

•Patient‐centered with next clinician of 

discharge instruction service 

• Timely follow‐up with 

ambulatory clinician 

Note: Individual components of these change packages have not been tested by 

themselves and might not reduce the risk for 30-day rehospitalization. 

Counseling 

opportunities 

for pharmacists 

Does Med Rec Impact the Patient Experience? 

Hospital Consumer Assessment of Healthcare Providers 

and Systems (HCAHPS) Domains: 

• Communication with Nurses 

• Communication with Doctors 

• Responsiveness of Hospital Staff 

• Pain management* 

• Communication about medicines* 

• Discharge information* 

• Cleanliness of hospital environment 

• Quietness of hospital environment 

• Overall rating of hospital 

• Willingness to recommend hospital 

Source: HCAHPS Fact Sheet. Available at: http://www.hcahpsonline.org/facts.aspx . Accessed 7/19/2012 

*Impacted by 

Medication 

Reconciliation and 

Patient Education 

MATCH Toolkit: A Step‐by‐Step Guide to 

Improving the Medication Reconciliation Process 

MATCH Toolkit, with 

customizable, actionable 

information, is available at: 

http://www.ahrq.gov/qual/ 

match/match.pdf 

Opportunities to Educate and Communicate 

Med 

History, 

Reconcile 

Order, 

Transcribe, 

Clarify 

Procure, 

Dispense 

Deliver 

Administer Monitor Educate, 

Discharge 

• Use Medication Reconciliation as an opportunity 

to educate patients throughout their hospital stay 

• EEmpower patients ti t to t ask k questions ti 

• Trace patients through hospitalization to identify 

opportunities for interaction 

ED Admission 

Intra‐ 

hospital 

Transfer 

Discharge 

Post‐ 

Discharge 

New CMS HCAHPS Care Transitions Questions 

(Effective January 1, 2013) 

• During this hospital stay, staff took my preferences and 

those of my family or caregiver into account in deciding 

what my health care needs would be when I left. 

• When I left the hospital hospital, I had a good understanding of 

the things I was responsible for in managing my health. 

• When I left the hospital, I clearly understood the 

purpose for taking each of my medications. 

Source: Centers for Medicare & Medicaid Services. Hospital Inpatient Prospective Payment Systems for Fiscal Year 2013 Rates. 42 CFR 

Parts 412, 413, 424, and 476 [CMS-1588-F]. Available at: http://www.ofr.gov/OFRUpload/OFRData/2012-19079_PI.pdf. Accessed 8/13/2012 

MATCH Toolkit: Excerpts on Medication History 

Taking and Patient Counseling 

• Asking open‐ended and closed‐ended questions 

• Inquiring about the types of physicians that prescribe their 

medications 

• Asking patients if their doctor recently started them on any 

new medicines, stopped medications they were taking, or 

made d any changes h to their h medications d 

• Asking patients to describe their medication by color, size, 

shape, etc., may help to determine the dosage strength and 

formulation 

• Educating about how and when to take their medications 

• Educating about the purpose of each medication 

8/29/2012 

3

Better Outcomes for 

Older adults through 

Safe Transitions 

• Guide and tool‐kit that promotes safe and 

hi high h quality li hospital h i ldi discharge h as they h 

transition through the hospital setting 

Project BOOST Team. The Society of Hospital Medicine Care Transitions Implementation Guide: Project 

BOOST: Better Outcomes for Older adults through Safe Transitions. Society of Hospital Medicine website, Care 

Transitions Quality Improvement Resource Room http://www.hospitalmedicine.org accessed 8/13/12. 




Interventions include: 

– Using teach back process during discharge 

education 

– Identifying readmission risk factors 

– Scheduling follow up visit or 72 hour phone call 

for high risk patients 

Prior 

hospitalization 

(6mo) 

Palliative 

Care 

Patient 

Support 

Problem 

Medications 

Psychological 

Principal 

8Ps 8 s Diagnosis 

Poor health 

literacy 

Polypharmacy 




• Goals 

– Reduce 30 day readmissions 

– IImprove patient i satisfaction if i scores 

– Improve flow of information 

– Identify high risk patients and develop interventions 

– Improve discharge preparation 

BOOST Resources 

• Risk Assessment Tool: The 8Ps 

• Plan Risk Specific Interventions 

Risk Specific Interventions 

• General Assessment of Preparedness (GAP) 

• Medications reconciled with preadmission list 

• Medications use and side effects reviewed 

using teach back with patients/caregivers 

• Teach Back used to confirm: 

– patient/caregiver understanding of diagnosis 

prognosis 

– self‐care requirements 

– symptoms of complications requiring medical 

attention 

8/29/2012 

4

Teach Back Process 

• Step 1 Explain information 

• Step 2 Patient repeats back in own words 

• Step 3 Identify and correct misunderstandings or 

incorrect procedures 

• Step p 4 Ask ppatient 

to demonstrate their 

understanding or procedural ability again to 

insure misunderstanding is corrected 

• Step 5 Repeat Steps 4 and 5 until clinician is 

convinced the pt comprehends the concept or 

ability 

Source: Schillinger D, Grumbach K, et al. Closing the Loop: Physician Communication With Diabetic 

Patients Who Have Low Health Literacy. Arch Intern Med. 2003;163(1):83-90. 

Thank You 

Carrie Vogler, Pharm.D., BCPS 

SIUE School of Pharmacy, y Edwardsville, IL 

Email: cvogler@siue.edu 

Kristine Gleason, RPh, MPH 

Northwestern Memorial Hospital, Chicago, IL 

Email: kmgleaso@nmh.org 

Medication Reconciliation/ 

Patient Counseling Activity 

8/29/2012 

5

I was in the hospital because: fluid overload, pneumonia 

Medication Reconciliation Discharge Paperwork 

Patient Discharge Medication List/Prescription Form 

The medical name for this condition is: acute heart failure 

I have these medical conditions: coronary artery disease, atrial fibrillation, diabetes, heart failure, high cholesterol, high blood pressure. 

Prescription 

Given? Medication name (use both names) 

How and how 

much? How often? What is it for? 

Next time 

I take? 

No Cordarone (amiodarone) 200mg 1 tablet by mouth once daily heart rhythm 9/14/2012 

No Aspirin 81mg 1 tablet by mouth once daily heart 9/14/2012 

No Folic acid 1mg 1 tablet by mouth once daily supplement 9/14/2012 

No Glucotrol (glipizide) 2.5mg 1 tablet by mouth once daily diabetes 9/14/2012 

Yes Cozaar (losartan) 25mg 1 tablet by mouth once daily blood pressure 9/14/2012 

Yes Levaquin (levofloxacin) 750mg 1 tablet by mouth once daily pneumonia 9/14/2012 

Toprol XL (metoprolol succinate) 

heart, 

No 

25mg 1/2 tablet by mouth once daily blood pressure 9/14/2012 

No Protonix (pantoprazole) 20mg 1 tablet by mouth once daily reflux 9/14/2012 

No Kdur (potassium chloride) 1 tablet by mouth twice daily supplement 

9/13/12 

evening 

No Zocor (simvastatin) 40mg 1 tablet by mouth 

once daily 

at bedtime cholesterol 9/13/2012 

No Aldactone (spironolactone) 25mg 1 tablet by mouth once daily water pill 9/14/2012 

Yes Demadex (torsemide) 20mg 4 tablets by mouth once daily water pill 9/14/2012 

Yes Coumadin (warfarin) 1mg 3 tablets by mouth 

once daily 

in pm blood thinner 9/13/2012 

LR 54 year old 

male 

Medications that 

have changed 

Dose increased 

from 12.5 mg to 

25mg once daily. 

Added. Take for 3 

days to complete 

treatment. 

Dose increased 

40mg to 80mg. 

Dose decreased. 

Stop warfarin 5mg 

If you have problems or questions about your health after leaving the 

hospital, please call the nursing unit. MD Signature _________ RN Signature________ 

Pharmacist Signature_________ Date________

Questions for Consideration and Discussion during this Exercise 

Using the patient’s Discharge Paperwork provided: 

1. How would you approach education and counseling for this patient taking into account your clinical practice site? 2. 

2. Is the patient’s medical history helpful when preparing to counsel patients? Why or why not? Do you receive the information you need in 

order to prepare for counseling sessions with your patients based on your practice site? Why or why not? 

3. What do you perceive are the barriers to effective counseling and education? 

4. What are the salient points that need to be conveyed to this patient during a counseling session? Why did you select those elements to 

counsel the patient on? 

5. The patient was admitted to the hospital for fluid overload and pneumonia. The patient was treated for acute heart failure. Please describe 

the educational elements that should be conveyed to a patient with heart failure during the counseling session, taking into account the 

heart failure process of care (e.g., core measures) (see below). 

6. How would you assess the patient's understanding of the information you provided during the patient counseling session? 

‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ 

Heart Failure National Hospital Inpatient Quality Measures [Process of Care (“Core”) Measures] 

HF‐1: Discharge Instructions: 

Heart failure patients with documentation that they or their caregivers were given written discharge instructions or other educational material 

addressing all of the following: 

1. activity level 

2. diet 

3. discharge medications (list of discharge medication names in the patient’s discharge summary and discharge instructions must match) 

4. follow‐up appointment 

5. weight monitoring 

6. what to do if symptoms worsen 

HF‐2: Evaluation of LVS Function: 

Heart failure patients with documentation in the hospital record that LVS function was evaluated before arrival, during hospitalization, or is 

planned for after discharge. 

HF‐3: ACEI or ARB for LVSD: 

Heart failure patients with left ventricular systolic dysfunction (LVSD) who are prescribed an ACEI or ARB at hospital discharge. For purposes of 

this measure, LVSD is defined as chart documentation of a left ventricular ejection fraction (LVEF) less than 40% or a narrative description of left 

ventricular systolic (LVS) function consistent with moderate or severe systolic dysfunction. 

Source: http://www.qualitynet ICHP Annual Meeting September 2012 

Carrie Vogler, Pharm.D., BCPS, Kristine Gleason, RPh,MPH

Putting Patient Safety First: 

Trends in Adverse Drug Event 

Screening and Reporting 

Charlene A. Hope, PharmD, BCPS 

Izabella Wentz, PharmD, FASCP ‐ Moderator 


TECHNICIANS 

1. Explain the difference between safety outcomes: adverse 

drug events, potential adverse drug events, medication side 

effects and medication errors. 

2. Identify three different approaches to Adverse Drug Event 

screening. i 

3. Name the types of outcomes associated with Adverse Drug 

Events. 

4. Review a tool implemented across various patient care 

settings for potential Adverse Event screening. 

5. Name two therapeutic and safety outcome measures. 

QIO Medication Safety Initiatives 

• Prescribing of 

PIM’s 

• PDP’ PDP’s/pharmacies 

/ h i 

/physicians 

8th SOW: 

2005‐2008 

PIM-Potentially Inappropriate Medication 

PDP-Medicare Prescription Drug Plan 

ADE-Adverse Drug Events 

9 

•Drug interactions 

th SOW: 

2008‐2011 •ADE’s & outcomes 

g 

• Clinical Pharmacy 

& PIM’s 

S Services i 

•PDP’s & Providers 

10th SOW: 

2011‐2014 


PHARMACISTS 

1. Differentiate between safety outcomes: adverse drug 

events, potential adverse drug events, medication side 

effects and medication errors. 

2. Identify three different approaches to Adverse Drug Event 

screening. 

3. Discuss current economic, clinical and humanistic 

outcomes associated with adverse drug events. 

4. Evaluate a tool implemented across various patient care 

settings for potential Adverse Event screening. 

5. Describe the types of therapeutic and safety measures 

that should be tracked to justify the expansion of clinical 

pharmacy services. 

About Quality Improvement 

Organizations 

• Telligen is the Medicare Quality Improvement Organization 

(QIO) for the state of Illinois, under contract with the Centers 

for Medicare & Medicaid Services (CMS). 

– Largest federal program dedicated to improving health quality at 

the community level 

• 1982:Peer Review Organizations (PRO’s) created by Congress 

• 1992: Medicare work of PRO’s redirected to Quality Improvement 

• 2002: Change of moniker to QIO to reflect mission 

– Work in three year long “Statements of Work” to improve care 

provided to Medicare beneficiaries 

– Provide technical assistance, resources and tools to providers 

and facilities throughout the state 

Check Point 

How many people are injured or die in hospitals 

each year from adverse drug events (ADEs)? 

0 000 

A. 770,000 

B. 220,000 

C. 560,000 

D. 1,200,000 

8/29/2012 

1

Why do we care about ADE? 

• Adverse drug events occur almost daily in medium‐sized 

hospitals and outpatient settings 

• 700,000 ED visits due to ADEs annually 

• 120,000 hospitalizations due to ADEs annually 

• $3.5 billion spent on ADE costs annually 

• At least 40% of ambulatory ADE costs preventable 

• ADE incidence rates: ranges from 2 per 100 admissions to 

7 per 100 admissions (AHRQ) 

• Can lead to permanent disability, depression, non‐ 

adherence, distrust in medical system and have a 

negative impact on quality of life. 

• 770,000 people are injured or die in hospitals each year 

from adverse drug events (ADEs) 

Opportunity for Clinical Pharmacy 

Services 

“Despite the high morbidity and mortality, 

physicians often do not recognize or 

appropriately treat instances of drug drug‐related related 

harm” 

Nebeker, et.al. Clarifying Adverse Drug Events: A Clinician’s guide 

to terminology, documentation, and reporting. Ann Intern Med. 2004; 

140:795-801 

The Adverse Drug Event Family 

Tree 

Inappropriate 

Medication Use 

Medication 

Errors 

Adherence 

ADE 

Appropriate 


ADR 

Side Effect 

Check Point 

How many people are injured or die in hospitals 

each year from adverse drug events (ADEs)? 

A. 770,000 0 000 people l 

“Tower of Babel” of Terminology 

Adverse Event 

Untreated 

Indication 

Drug Related 

Problem 

Inappropriate Monitoring 

Non‐ 

adherence 

Potential 

Adverse Drug 

Event 

Medication 

Error 

Side Effect 

Adverse Drug 

Event 

Adverse Drug 

Reaction 

Definitions Related to Drug Related Harm: 

HARM OCCURRED 

Term Definition 

Adverse event Harm in a patient administered a drug that was not 

necessarily caused by a drug 

Adverse Drug Harm caused by drug with normal use that is not 

RReaction ti (ADR) expected t d 

Adverse Drug Event 

(ADE) 

Harm caused by the use of a drug or the 

inappropriate use of a drug 

Adapted from: Nebeker, JR et .al. Clarifying Adverse Drug Events: A Clinician’s 

Guide to Terminology, Documentation, and Reporting. Ann Intern Med. 2004; 

140:795‐801 

8/29/2012 

2

True of False 

1. An ADR is always an ADE 

Definitions Related to Drug Related 

Harm: HARM DID NOT OCCUR 

TERM DEFINITION 

Potential Adverse Drug Event (pADE) Circumstances that could result in harm 

by the use of a drug, but that did not 

result in harm to the patient 

Adapted from: Nebeker, JR et .al. Clarifying Adverse Drug Events: A Clinician’s Guide 

to Terminology, Documentation, and Reporting. Ann Intern Med. 2004; 140:795‐801 

True of False 

• A potential adverse drug event did not result 

in patient harm TRUE 

True of False 

1. An ADR is always an ADE 

2. An ADE is always an ADR 

True of False 

• A potential adverse drug event did not result 

in patient harm 

Definitions Related to Drug Related 

Harm: HARM MAY HAVE OCCURRED 

TERM DEFINITION 

Medication Error Inappropriate use of a drug that may 

or may not result in harm 

Side Effect A usually predictable effect of a drug 

that is not the intended effect, may 

be desirable, undesirable or 

inconsequential (not usually 

considered when reporting adverse 

events) 

Adapted from: Nebeker, JR et .al. Clarifying Adverse Drug Events: A Clinician’s 

Guide to Terminology, Documentation, and Reporting. Ann Intern Med. 2004; 

140:795‐801 

8/29/2012 

3

True or False 

• Medication errors always result in patient 

harm 

Inappropriate 


ADE 

Medication 

Errors 

Appropriate 


ADR 

Adherence Side Effect 

Adverse Drug Events due to 

Inappropriate Medication Use 

Medication Errors 

• 7000 deaths annually in the US, increase the 

annual operating costs of a 700 bed hospital 

by $3 million dollars 

Bates, et al. The costs of adverse drug events in hospitalized patients. Journal of the American Medical 

Association. 1997; 277: 307‐311 

True or False 

• Medication errors always result in patient 

harm 

• Side effects are predictable effects of 

medications 

Medical Errors 

• Between 44,000‐98,000 people die each year in 

hospitals due to medical errors. 

• 2000 study in Australia: 50,000 people became 

disabled as a result of medical errors annually 

• 2 million people suffer healthcare acquired infections 

which adds up to: 88,000 deaths, and a cost of $5 

billion 

Kohl et al. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 1991:1. 

Weingart, et al. Epidemiology of medical error> British Medical Journal. 200; 320: 774‐777 

Hospital infections cause US billions of dollars annually. Centers for Disease Control and Prevention Website. 

Available at httP://www.cdc.gov/media/pressrel/r2k0306b.htm. Accessed July 22nd, 2012 

Medication Errors 

Reducing and Preventing Adverse Drug Events To Decrease Hospital Costs. Research in 

Action, Issue 1. AHRQ Publication Number 01-0020, March 2001. Agency for Healthcare 

Research and Quality, Rockville, MD. http://www.ahrq.gov/qual/aderia/aderia.htm 

8/29/2012 

4

Non‐Adherence 

• Drug‐Related Problems 

– Treatment failures due to possible non‐adherence 

with medication regimen: 

– Total estimated cost is $100 billion annually 

• Approximately 2 million hospital readmissions 

each year can be traced to non‐adherence 

• Approximately 125,000 Americans die each year 

because of non‐adherence 

• Intentional vs. non‐intentional 

Arch Intern Med. 2008(116):565‐71. 

Am J Health‐Syst Pharm. 1998(55)1:1127‐33. 

Adverse Drug Reactions 

• 2 million adverse drug reactions 

• 100,000 fatalities 

• One of the leading causes of death in the 

United i dS States. 1 

Institute of Medicine, National Academy Press, 2000 

Lazarou J et al. JAMA 1998;279(15):1200–1205 

Gurwitz JH et al. Am J Med 2000;109(2):87–94 

Adverse Drug Events (ADE) 

Non‐ 

adherence 

Adverse 

Drug 

Reactions 

Medication 

Errors 

Drug 

Events 

Inappropriate 


ADE 

Medication 

Errors 

Appropriate 


ADR 

Adherence Side Effect 

Adverse Drug Events due to Adverse 

Drug Reactions 

Costs Associated with ADR 

• $136 billion annual costs 

• ADRs cause 1 out of 5 injuries or deaths per 

year to hospitalized patients 

• Mean length of stay, stay cost and mortality for 

ADR patients are DOUBLE that for control 

patients 

Johnson JA et al. Arch Intern Med 1995;155(18):1949–1956 

Leape LL et al. N Engl J Med 1991;324(6):377–384 

Classen DC et al. JAMA 1997;277(4):301–306 

Pharmacist Role in ADR Reporting 

ASHP Guidelines on Adverse Drug Reaction Monitoring and 

Reporting 

It is the pharmacist’s responsibility and professional obligation to 

report any suspected ADRs. 

ASHP PPMI 

Optimal pharmacy practice models: Characteristics, requirements, and challenges 

B19. Pharmacists should actively monitor for and report 

potential and actual adverse drug events 

The consensus of the Pharmacy Practice Model Summit Am J Health-Syst Pharm. 2011; 68:1148-52 

8/29/2012 

5

Check Point 

Which of the following methods does your 

institution utilize to identify adverse events 

(ADE, ADRs and Medication Errors)? Choose all 

that apply apply. 

a. Incident Reporting 

b. Direct Observation 

c. Chart Review 

d. Trigger Tools 

Quantification of DRPs 

Meyer-Massetti C, Cheng CM, Schwappach DLB et al. Systematic review of medication safety assessment methods. 

Am J Health-Syst Pharm. 2011; 68:227-240. 

Resource Utilization 

Direct Observation 

Chart Review 

Incident Review 

Trigger Tool 

Meyer‐Massetti C, Cheng CM, Schwappach DLB et al. Systematic review of medication safety assessment methods. 

Am J Health‐Syst Pharm. 2011; 68:227‐240. 

Meyer‐Massetti C, Cheng CM, Schwappach DLB et al. 

Systematic review of medication safety assessment methods. 


Purpose: To compare the accuracy, efficiency, and efficacy of 

commonly used medication safety methods in proactive 

medication safety assessment. 

Methods: Medical literature databases were search over a nine 

year period for any comparative study with at least two of four 

methodologies –incident report review, direct observation, 

chart review and trigger tool. Studies were included in the 

analysis if they included efficiency (effort and cost), and efficacy 

and provided numerical data. 

Accuracy of DRPs 

• Sensitivity, Specificity and Positive Predictive 

Value of the different DRP assessment 

methods varied greatly. 

• Incident report review were generally more 

specific than other methods 

• When compared to trigger tools, incident 

report review was consistently less sensitive. 

• PPV of trigger tools ranged from 0% to 100% 

Meyer‐Massetti C, Cheng CM, Schwappach DLB et al. Systematic review of medication safety assessment 

methods. Am J Health‐Syst Pharm. 2011; 68:227‐240. 

Hanlon JT, Maher RL, Lindblad CI, et. al. 

Comparison of methods for detecting potential adverse drug events in 

frail inpatients and outpatients. Am J Health‐Syst Pharm. 2001; 58:1622‐6 

Purpose 

1. Compare the rates of potential ADEs identified from self‐reports along and from 

self reports combined with chart reviews 

2. Determine the number of potential ADEs identified from self‐reports that were 

plausible ADEs 

3. Determine the time required to apply various ADE‐screening methods 

4. Calculate the prevalence of chart ADE screens leading to ADE evaluations 

5. Describe the interpreter reliability of ADE screens applied separately by a nurse 

and a pharmacist 

Methods 

Multi‐centered, conducted at 11 Veteran Affairs Medical Centers (VAMCs) 

Patients eligible if they were>65 years old, hospitalized on a medical or surgical ward 

for >48 hours, and were frail. 

8/29/2012 

6


Comparison of methods for detecting potential adverse drug events in 

frail inpatients and outpatients Am J Health‐Syst Pharm. 2001; 58:1622‐6 

Methods, cont 

• Five ADE screening methods were used 

– Surveillance for tracer drugs, 

– SSurveillance ill for f narrow‐therapeutic‐index h i i d ddrugs 

– Screening for changes in medications 

– Screening for previously identified ADEs 

– ADE‐tracking reports 


Comparison of methods for detecting potential adverse drug 

events in frail inpatients and outpatients Am J Health‐Syst 

Pharm. 2001; 58:1622‐6 

Tracking Reports, 

Narrow 

Therapeutic‐ 

Index drugs, 

TTracer Drugs D 

Chart Review 

Method (changes 

in medications 

and previously 

identified ADEs) 

• Occurs through computer 

surveillance 

•Most Efficient 

•Least yield to generate an 

actual report 

•Traditional Method 

•Time consuming and costly 

• Generated the highest yield 

leading to an actual report 

National Coordinating Council for Medication Error 

Reporting and Prevention (NCC‐MERP Index) 

NCC MERP. accessed August 2012. www.nccmerp.org 


Comparison of methods for detecting potential adverse drug events in frail 

inpatients and outpatients Am J Health‐Syst Pharm. 2001; 58:1622‐6 

Table 1. Prevalence and Efficiency of Chart ADE Screens Assessed by a Pharmacist (n=50) 

Screening Method % Positive ADE Screens 

Leading to ADE 

Summaries 

Minutes Needed to Screen for 

Potential ADEs (Mean + S.D.) 

ADE‐tracking reports 2 1.85 + 3.47 

Narrow‐therapeutic‐ Narrow therapeutic 

index drugs 

4 2.68 + + 2.09 

Tracer drugs 6 7.78 + 4.40 

Changes in 

medication 

42 17.13 + 9.65 

Previously identified 

ADEs 

52 10.71 + 5.89 

Audience Participation 

How many sites currently reporting potential or 

preventable adverse drug events? 

Classifying Medication Errors 

NCC‐MERP Index 

A circumstances exist for potential errors to occur 

B an error occurred but did not reach the patient 

C error reached the patient but did not cause harm 

D patient monitoring required to determine lack of harm 

E error caused temporary harm and some intervention 

F temporary harm with initial or prolonged hospitalization 

G error resulted in permanent patient harm 

H error required intervention to sustain the patient’s life 

I error contributed to the patient’s death 

NCC MERP. accessed August 2012. www.nccmerp.org 

8/29/2012 

7

Proactive Screening Process Patient Demographic Information 

Intervention Documentation 

• One intervention per row 

• Name(s) of drug(s) involved 

• Indication(s) for drug 

• Intervention codes 

Medication‐Related Problem 

(MRP) 

• Date of intervention 

• Site 

• Medical record number (MRN) 

• Date of birth (DOB) 

• Gender 

• Insurance 

• Ethnicity & Language 

Intervention Codes 

• 4 parts to match columns in intervention section 

I. Medication‐Related Problem (MRP) 

II. ADE/pADE Classification 

III. pADE Severity Rating 

IV. Intervention/Recommendation 

Intervention Codes 

ADE/pADE Classification 

8/29/2012 

8

Intervention Code 

Potential ADE Severity Rating 

Description of Event 

• Provides clarification of event and 

likelihood of its association with the drug 

Audience 

Participation 

Based on patient 

case: 

How would you 

classify the 

identified pADE? 

*Note: This has been edited from the manual to reflect the chart description. 

Intervention Code 

Intervention/Recommendations 

Patient Case 

RH is a 57 y/o Male admitted for right foot abscess, cellulitis, 

anemia, hypokalemia, and acute kidney injury 

PMH: Seizures, Asthma, chronic back pain, Crohn's Disease 

Upon review of the patient medication profile, the pharmacist 

discovers that the patient has been receiving Sulfadiazine 

500 mg po Q6hr instead of Sulfasalazine 500 mg po Q6hr. The 

physician was called and order was corrected. 

Audience 

Participation 

Based on patient 

case: 

What severity 

What severity 

would you 

classify this 

pADE? 

8/29/2012 

9

MTI Pilot at NAH 

PharmD Students 

trained on the MTI form 

DRP screening occurred 

over 6 week period 

Data compiled 

MTI Pilot Results 

Time period: 6 weeks 

Total Number of patients: 50 

Total Number of MRPs: 48 

Patient Demographics 

Age 

Gender 

Race 

18‐30 y/o : 4% (2) 

31 31‐50 50 y/o: 36% (18) 

>51 y/o: 60% (30) 

Male: 56% (28) 

Female: 44 % (22) 

African‐American: 34% (17) 

Caucasian: 12% (6) 

Hispanic: 54% (27) 

pADE Classification 

Safety 

Metrics 

•Health 

Information 

System 

Revised 

Clinical 

Intervention 

Tracking 

Module 

8/29/2012 

10

Revise Clinical Intervention Module 

Appropriate and Effectiveness 

Safety (pADE/ADE) 

Non Adherence and Patient Variables 

Miscellaneous 

pADE/ADE Classification 

pADE Severity Rating 

Educate Pharmacists, APPE PharmD Students 

One on One orientation/training 

1 hour presentation included as a part 

of site orientation (paper and computer) 

Safety (pADE/ADE) 

• Abnormal lab 

• Allergy 

• Contraindication 

• Illegible Order 

• Incomplete Order 

• Order Clarifications 

• Drug Dose Excessive for 

therapeutic Goals 

• Therapeutic Duplication 

Updated Clinical Intervention 

Documentation 

Time period: 4 week period 

Total Number of Clinical 

Interventions documented 

Total Number of interventions 

sampled 

636 

69 

Number of MRPs reviewed 69 

pADE 

Classification 

Cost Avoidance 

Occurrence Rate 3% 

Average Cost of ADE $ 2182 

Yearly Projection of 

Med Intervention 

7261 

Estimated ADEs 

avoided (Annualized) 

218 

Estimated Savings $ 475,298 

Adapted from Medication Reconciliation Tracking Tool. John Hopkins University. Accessed at: 

http://www.ihi.org/knowledge/Pages/Tools/ReconciliationTrackingTool.aspx on 8/6/12 

8/29/2012 

11

ASHP PPMI Case Study 

Adding Value: Prevention Prescribing Errors through 

Pharmacist Interventions Utilizing a Severity Rating Scale 

Relevant PPMI Recommendation 

B24. Every pharmacy department should: 

m. Track and trend pharmacist interventions 

• Pi Primary IIntended t d dOOutcome t 

– Demonstrate clinical relevance, via use of a 

severity rating scale, of prescribing errors 

intercepted by pharmacists 

Palmer K, Shane R Adding Value: Preventing Prescribing Errors through Pharmacist Interventions Utilizing a Severity Rating Scale 

http://www.ashpmedia.org/ppmi/case-studies.html, Accessed August 6, 2012. 


• Outcome Measures 

– Demonstrated the value of clinical pharmacy services to 

the organization 

– Did not result in an increase FTE; however, it supported 

the need for pharmacist staffing throughout the patient 

care areas. 



Post Test Case Study 

60‐year‐old Hispanic female who presents for diabetes MTM. 

She has been experiencing what she describes as ~10 “really 

bad” hypoglycemic episodes since her last visit with her 

primary care provider. She claims that she has not changed 

her diet nor activity level. She checked her blood glucose 

levels during g several of these episodes p and the readings g 

ranged from 60 to 70 mg/dL; she managed these episodes by 

consuming fruit juice or bread and rechecking her blood 

glucose every 15 minutes as directed. Upon completing your 

medication reconciliation, you find out that her dose of 

glyburide was recently increased from 10 mg BID to 20 mg 

BID. 


• Pharmacists document intercepted prescribing errors and their 

potential severity, utilizing the NCC MERP Index in the electronic 

health record. 

• Analyzed Data used in numerous ways 

– Included in the hospital performance improvement program 

– Reported to P&T Committee and Medical Staff Committees 

• Physician Education 

• Medical Staff Credentialing process 

– Pharmacy Department 

• Clinical Skills Assessment for pharmacy residents 

• Shared with pharmacy staff on a routine basis 



References 

1. Bates et. al. Incidence of adverse drug events and potential adverse drug events. Implications for 

prevention. ADE Prevention Study Group. JAMA. 1995; 274:29‐34 

2. Gandhi et. al. Adverse drug events in ambulatory care. N Engl J Med. 2003;348:1556‐64 

3. Fattinger, et al. Epidemiology of drug exposure and adverse drug reactions in two Swiss deprtmetns of 

internal medicine. Br J Clin Pharmacol. 200;49:158‐67 

4. Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of 

emergency department visits for outpatient adverse drug events. JAMA 2006;296:1858‐66. 

55. Institute of Medicine Medicine. Committee on Identifying and Preventing Medication Errors Errors. Preventing Medication 

Errors, Washington, DC: The National Academies Press 2006. 

6. Classen DC, Pestotnik SL, Evans RS, et al. Adverse drug events in hospitalized patients. JAMA 

1997;277(4):301‐6. 

7. Cullen DJ, Sweitzer BJ, Bates DW, et al. Preventable adverse drug events in hospitalized patients: A 

comparative study of intensive care and general care units. Crit Care Med 1997;25(8):1289‐97. 

8. Cullen DJ, Bates DW, Small SD, et al. The incident reporting system does not detect adverse drug events: A 

problem for quality improvement. Journal on Quality Improvement 1995;21(10):541‐8. 

Case Study Question 

1. This adverse event is ___________________ 

and an example of a(n)__________________. 

a. inappropriate medication use, Side Effect 

b i di i dh 

b. appropriate medication use, Non‐adherence 

c. inappropriate medication use, Medication 

Error 

d. appropriate medication use, Adverse Drug 

Reaction 

8/29/2012 

12

Assessment Question 

2. Which of the following methods of screening 

for Adverse Drug Event events is considered to 

be the most time efficient? 

aa. Direct Observation 

b. Trigger Report 

c. Chart Review 

d. Incident Reporting 


4. How many hospital re‐admissions each year 

are due to non‐adherence? 

a. 40,000 

bb. 250 250,000 000 

c. 1 million 

d. 2 million 


3. A Potential Adverse Event is a circumstance 

that could result in harm by the use of a drug, 

but that did not result in harm to the patient 

aa. True 

b. False 


5. The Medication Therapy Intervention Form 

incorporated the tracking of which safety 

outcomes? 

aa. Potential Adverse Drug Events and Medication 

Errors 

b. Adherence and Adverse Drug Events 

c. Medication Errors and Adherence 

d. Potential Adverse Drug Events and Adverse Drug 

Events 

8/29/2012 

13

Interdisciplinary Teamwork: 

How Physicians, Nurses and 

Pharmacists Can Work Together 

Mark Loafman MD, MD MPH 

Assistant Professor Family Medicine, 

Northwestern Feinberg School of Medicine 

National Faculty Co‐Chair, HRSA Patient Safety 

and Clinical Pharmacy Services Collaborative 

No Conflicts of Interest to disclose 

Learning Objectives Cont. 

• Recognize the value in defining a small population of focus as 

a starting point in the work of systems improvement. 

• Translate the application of the practices outlined in the 

Patient Safety Clinical Pharmacy Services Collaborative (PSPC) 

Change Package to the unique needs of the participant participant’s s 

home organization. 

• Define mechanisms by which an organization can facilitate 

success in integrating clinical pharmacy services into chronic 

care treatment and clinical programs. 

If sick patients held Olympics, how 

may medals would the U.S. win? 


• Identify the critical emerging role for clinical pharmacy and safe Rx 

use in achieving the triple aim for patient centered health care 

services. 

• Describe the knowledge and systems barriers known to adversely 

affect care providers’ ability to achieve optimal health outcomes in 

patients i with ihchronic h i conditions. di i 

• Articulate how integrating clinical pharmacy services into an inter‐ 

professional team can address systems barriers to optimal care. 

• Explain the Institute for Healthcare Improvement (IHI) Collaborative 

Model for Breakthrough Improvement in terms of rapid cycle 

improvement involving clinical pharmacy services. 

2 

Allocation of Health Care Resources and Workforce 

Allocation of Healthcare Resources and Workforce 



…. and what it takes to get our attention 

‐HTN, Diabetes, Obesity, 

Dyslipidemia, Tobacco 

‐ Cancer 

‐ Trauma, Accidents 

8/30/2012 

1



…. in comparison to Population w/chronic disease 

Patients with 

Chronic Disease 

Patients with 

Advanced Stage 

Disease 

Patients who are dying 

Life Course Perspective –Current Delivery System 

Trajectory for Chronic Disease 

• Diabetes 

•HTN, Lipids 

•Obesity 

• Smoking 

w/o Primary 

Prevention 

w/o Secondary 

Prevention 

• Vasculopathy 

•CV and Renal 

damage 

• Mild Disability 

•ESRD, MI, CVA 

•Heart, Kidney 

Failure 

• Severe Disability 

• Mild Disability Severe Disability 

End Stage Care ‐ 

Death 

Life Course Perspective –NewDelivery System 


• Diabetes 


•Obesity 

• Smoking 

Primary 

Prevention 

w/o Secondary 

Prevention 



damage 




Failure 



• Minimal vascular 

disease 

•Preserved Heart, 

Kidney Function 


Death 

End Stage 

Care ‐ Death 

Epidemiology 

• Chronic disease = highly prevalent 

• Uncontrolled chronic conditions = highly 

prevalent 

• Epidemic id i of f uncontrolled ll d chronic h i conditions di i 

Life Course Perspective –Current Delivery System 


• Diabetes 


•Obesity 

• Smoking 

w/o Primary 

Prevention 

w/o Secondary 

Prevention 



damage 




Failure 




Death 

What do patients need to do to get our attention? 

What does it take to get our best care? 

Health Care Resources, Workforce and Population 

Many Patients 

with 

Uncontrolled 

Chronic Disease 

Many Patients with 

Controlled Chronic 

Disease 

More Patients 

with Advanced 

Stage Disease 

Patients dying 

younger and sicker 

Less Patients with 

Advanced Stage Disease 

Patients still die, but 

later and “better” 

8/30/2012 

2

Highly Effective Healthcare 

• What does “world class” care look like? 

• Examples 

– Historical 

– CContemporary 

• Opportunity 

How Reliable is our Care? 

A function of System and Culture 

Autonomy Teamwork Highly Reliable Organizations 

Chaos Error 1:10 1:100 1:10,000 1:1 million 

Custom‐ Standard Standard 

crafted training, process, 

processes ttry hard h d hbit habits and d 

patterns 

Each Doctor 

writes 

individual 

orders 

Each staff 

member has 

his/her own 

way 

Multi‐ 

disciplinary 

rounds 

Deference to 

expertise, 

“ “safety f t 

culture” 

Blood banking, 

Approval for 

high risk 

orders 

Loss of 

individual 

id identity tit 

Yes but, it’s like herding cats 

What we say What doctors hear 

• Performance improvement ‐ You doubt my judgment 

• Accountability ‐Insult my integrity 

• Collaborative practice ‐ Losing control 

• Electronic Records ‐ OMG! 

• Guidelines ‐ Cookbooks 

Achieving the Triple AIM 

14 

Integrated CPS 

Health Status 

Adverse Drug Events 

Anesthesia 

safety, airline 

industry Engaging Physicians in 

Performance Improvement 

Understanding the frustration 

• Satisfaction with practice has decreased for 

many physicians. 

• The “psychological contract” has been 

changed changed, without informed consent consent. 

• Professional ethos that got them here is no 

longer working. 

8/30/2012 

3

PSPC 

Working 

Here 

The Breakthrough Model for Improvement 

• Who “owns” performance improvement in our shop? 

• Can we use the Model for Improvement and Clinical 

Pharmacy Services to attack our “to do” list? 

Pharmacy Services to attack our to‐do list? 

• Are we ready to adopt a bold new approach for Quality 

Improvement? 

• The most important next step I can take is…? 

Where PDSA’s have taken us: 

Magnitude of the possible scale‐up and spread of CPS 

833,936 patients 



3,369 

patients 

A. Population of Focus (PoF) 

for detecting improvement in 

PSPC 

D. Total Population of Care 

(PoC) for primary health 

care home 

C. Population of Service (PoS) 

for CPS. The total high risk 

patient population seen by the 

primary health care home that 

can benefit dramatically from 

integrated CPS 

B. Population of Focus at Scale Up. 

Total number of patients with same PoF health 

status marker conditions and risks 

Performance Improvement 

as Translational Research 

IHI Breakthrough Model for Improvement 

Breakthrough Improvement Model: 

Key Attributes 

• Patient‐Centered 

• Inter‐professional care team 

• Cross‐organizational with health/medical homes at the 

center 

• An approach to spread to many other conditions 

• Systematically addresses medication management, 

safety and risk 

• PDSA cycles for rapid improvement 

• Is not new work to do, but a powerful new way to do 

the work we already have 

Inter‐Professional Teams 

• If Healthcare were a movie for our patients 

with chronic conditions, what kind of 

Soundtrack would there be? 

• Typical patient has …. 

8/30/2012 

4

Inter‐Professional Teams ‐ 

Changing the Soundtrack 

• Clinical Integration 

– Interdisciplinary teams are needed to address 

complex issues primary care providers face. 

– With so much to do, each discipline must function 

at the highest level of their skill and training. 

– While the Patient Care Medical Home is a step in 

the right direction, it is not powerful enough alone 

to deliver the outcomes we are seeking. 

Clinical Integration: Achieving 

�Create time for physicians 

◦ Documentation tools, protocols, care maps 

◦ Standardize/enhance Allied Health staff 

◦ Reduce “non‐productive” time 

�Generate value for physicians 

◦ Help achieve quality/satisfaction goals 

◦ Financial incentives and support 

◦ Share technology, resources and even staff 

Putting it all together: Breakthrough Model to Drive Change: 

Improvement Model, CPS, Clinical Integration 

• Consistent use of clinical practice 

guidelines, standing order sets, etc. 

• Use allied health at highest level possible, 

working ki as a tteam 

• Standardized documentation templates 

• Changing and refining practices in response 

to performance data 

Inter‐Professional Teams ‐ Approach to Clinical Integration 

• Process 

– Case and Disease management 

– Doing things right 

– Get patient to the right place at the right time 

– PPush hagainst i tnon‐Compliance C li 

• Outcomes 

– Patient centered care coordination 

– Doing the right things 

– Achieving optimal health measures 

– Safe and Effective Medication Use 

Inter‐Professional Teams 

Clinical Integration 

• Levels of Integration 

– Referral 

– Colocation 

– Fully integrated 

Interdisciplinary Teamwork: 

How Physicians, Nurses and Pharmacists 

Can Work Together 

“Answering Answering the Call to Action” Action 

Mark Loafman MD, MPH 

Assistant Professor Family Medicine, Northwestern 

Feinberg School of Medicine 

National Faculty Co‐Chair, HRSA Patient Safety and 

Clinical Pharmacy Services Collaborative 

8/30/2012 

5

Post Test Question 

1. Match the drug name on the left with the 

brand name on the right. 

_ Abacavira) b i ) Isentress 

_ Raltegravir b) Norvir 

_ Ritonavir c) Sustiva 

_ Efavirenz d) Ziagen 


1. SV is a 34 year old female who was recently diagnosed HIV+ 

and who would like to start treatment. What are the two 

most important laboratory parameters that her health 

provider needs to determine if HIV treatment should be 

initiated? 

a. CD4 T‐lymphocyte count and fasting lipid profile 

(triglycerides, total cholesterol, LDL, HDL). 

b. HIV viral load and CD4 T‐lymphocyte count 

c. HIV viral load and serum creatinine 

d. CD4 T‐lymphocyte count and liver enzyme tests 


5. Which of the following adverse effects is 

specific for atazanavir (Reyataz) 

a. renal toxicity 

b ii 

b. Hepatitis 

c. elevated triglycerides 

d. elevated bilirubin 


2. Which of the following regimens is recommended for 

the 2012 Department of Health and Human Services 

Treatment Guidelines for initial therapy for HIV 

infected adults? 

a. Truvada (tenofovir/emtricitabine) + ritonavir 

b. Complera (tenofovir/emtricitabine/rilpivirine) 

c. Combivir (zidovudine/lamivudine) + atazanavir 

d. Atripla (tenofovir/emtricitabine/efavirenz) 


4. Which of the following adverse effects is 

associated with tenofovir? 

a. renal toxicity 

bb. Dizziness i i 

c. elevated triglycerides 

d. rash 

8/30/2012 

6

Meeting the PPMI Goals for Technology – 

“Is a Puzzlement” 

Drug Bug Mismatch 

Dima Awad, Pharm.D, MS 

Assistant Director of Pharmacy, Informatics, and Technology 

University of Chicago Medicine 

Chicago, Illinois 

The speaker has no conflict to declare. 

Introductions 

• How many of you have implemented an Antimicrobial Stewardship 

Program? 

• How many of you have implemented Clinical Decision Support Tools 

integrated with CPOE (Computerized Physicians Order Entry)? 

PPMI Goals Related to Clinical Decision 

Support 

• C2d. Clinical decision support integrated with CPOE. 2 

• C2e. Order management and review organized around 

drug therapy management services. 2 

• C2f. Real-time monitoring systems that provide a work queue of 

patients needing review and possible intervention. 2 

2 Am J Health-Syst Pharm—Vol 68 Jun 15, 2011 1151 

University of Chicago Medicine 

• A Non-For-Profit Hospital 1 

– Bernard A Mitchell Hospital 

– Comer Children’s Hospital 

– Chicago Lying-in Hospital 

– Duchossois Center for Advanced Medicine (DCAM) 

– University of Chicago Pritzker School of Medicine 

– NHP Pavilion set to open February 2013 

• Patient Care Facts circa 2011 1 

Fact 

Admissions 22,797 

Average Beds in Service 550 

Visits to DCAM 384,550 

Emergency Visits 74,359 

1. UCM Intranet. University of Chicago Medicine. 13 August, 2012. 

Self Assessment 

• Which PPMI goals are associated with clinical decision support? 

A. Order management and review organized around drug therapy 

management services. 

B. Real-time monitoring systems that provide a work queue of 

patients needing review and possible intervention. 

C. Both A and B 

D. Avoid at all costs, could trigger a migraine. 


• Recognize the PPMI goals related to clinical decision support 

implementation. 

• Describe the functionality of antibiotic monitoring. 

• Discuss the challenges and solutions associated with the antibiotic 

monitoring build. 

8/29/2012 

1

• Drug Bug Mismatch 

Clinical Decision Support 

Clinical Tools For Improved Patient Safety 

• Antimicrobial Stewardship Program (ASP) 

• Alerts user when patient’s culture is resistant to their current 

antimicrobial therapy 

Preceding Surveillance Tools 

• Electronic Medical Record 

– Clarity reports 

• Data not available until next day 

– Reporting Workbench 

• Inability to link culture with patient’s antimicrobials 

Culture 

Resulted 

Triggers BPA 

Criteria/Rule 

Drug Bug Workflow 

Sends In Basket 

Message 

Clinician reviews 

antimicrobial 

therapy then 

contacts 

provider 

Clinician adds 

pass off note and 

marks message 

as done 

Antimicrobial Stewardship Program 

• 3 The UCMC Antimicrobial Stewardship Program (ASP) is charged 

with 

– improving antimicrobial prescribing practices 

– enhancing the safety of antimicrobial use 

– ensuring the cost-effective use of antimicrobial agents 

• 4 “Computer based surveillance can facilitate good stewardship by 

more efficient targeting of antimicrobial interventions” 

3. ASP Intranet. University of Chicago Medicine. 13 August, 2012. 

4. Dellit t, Owens R, McGowan J et al. Infectious Diseases Society of America and the Society for Healthcare epidemiology of America guidelines for 

Developing an Institutional Program to Enhance Antimicrobial Stewardship. CID 2007:44: 159-173 

Drug Bug Mismatch 

Challenges/Solutions 

• Challenges 

– New functionality 

– Complex logic equals a large build 

– Multiple organism cultures = Multiple Messages 

• Solution 

– Build basic rules and put the details in the report 

Drug‐Bug Mismatch Example 

• A patient’s culture is resulted which is resistant to their current 

antimicrobial medication order (e.g. Ceftazidime) 

• Alert triggered 

8/29/2012 

2

Drug‐Bug Mismatch Example Con’t 

• Alert sends and In Basket message to the ASP team 

• Clinician utilizes message time to determine resistant culture to 

patient’s antimicrobial 

In‐Basket Message 


• Clinician reconciles antibiotics 

• In Basket buttons allow access to patient’s chart for further evaluation 

• Clinician may add comments about patient’s antimicrobial therapy. 

Drug‐Bug Mismatch Build 

General Table/VCG 

• General Table 

• Maps antibiotic to medication records 

•VCG 

• groups medication records 

• one VCG group for each antibiotic 

☺ for easier maintenance use generic medication med 


• In Basket report consolidates patient information for review by 

clinician. 

• Patient demographic information 

• Active anti-infectives 

• Latest culture results 


• Components 

• General Table/VCGs 

• Best Practice Alerts (BPA) 

• Rules 

• In Basket 

• Report/Print groups 

• Estimated build time one month >> Depends on the build! 

p 


General Table/VCG 

•General Table/VCG Example 

8/29/2012 

3


Best Practice Alerts 

•BPA 

•Triggered when culture resulted 

• Multiple settings allow for further customization of criteria 

• Restrict to inpatient anti-infective orders 

• Restrict to certain hospitals 

• Link to rules 

•Sends In Basket message if all criteria are met 

• Customize In Basket message 

• Assigns In Basket pool 



•BPA base In Basket setup 

Assigns In Basket pool 



•BPA criteria example 

Link to Rule 



•BPA base example 

Additional 

Restrictions 

Triggering Action 



•BPA criteria example 

Both Criteria need to be true for 

BPA to send in-basket message 


Rules 

•Rules 

• Processes each line of the culture 

• e.g. CEFTAZIDIME RESISTANT 

• Compares general table VCG (CEFTAZIDIME) to patient’s active 

medications. 

• Custom logic allows flexibility in rules 

8/29/2012 

4


Rules 

•Rules Example 

• Rule is true if patient is on an active antibiotic order that is 

resistant or intermediate. 

Custom logic allows for further flexibility 


In Basket 

•In Basket Setup – A Presentation in Itself! 

• Recipients of message are assigned to a message pool 

• Message type defines In Basket build 


In Basket Report 

•Report 

• Consolidate information in one location 

• Customized print groups 

• Patient demographics 

• Pharmacist pass off note 

• Active antibiotics 

• Discontinued antibiotics 

• Culture results 


Rules 

•Rules Example con’t 

• Line #2 Maps Culture Antibiotic to Patient’s Active Antibiotics 

PATIENT.Active Medication Orders.Medications.Groupers = PATIENT.Culture Results.Sensitivities.Antibiotic Grouper 


In Basket 

•In Basket Buttons 

• Command Buttons 


In basket Report 

• Custom print groups 

• Active antibiotics 

• Print Group # 46100 

• Must create LPP filter to only list antibiotics 

• Pharmacist pass off note “Sticky Note” 

• Print Group #46541 

• Must assign a key to sticky note (e.g. RXDRUGBUG) 

• Note is per patient encounter 

8/29/2012 

5

Limitations 

• No functionality exists to indentify triggering culture/antibiotic 

- Work around: clinician must match time of message to time of 

culture result then reconcile antimicrobials. 

• Rule cannot restrict to only inpatient antimicrobials 

- Work around: BPA criteria requires that the patient is on at least 

one active inpatient anti-infective 

•Clinicians have no way to mark an alert as reviewed 

- Work around: created pharmacist pass off note. 

• Cultures can have several “Preliminary Results”, which trigger 

duplicate messages. 

Enhancements 

• Print group to identify triggering culture/antibiotic 

• Rules specific to inpatient medications 

• Ability to mark messages as reviewed 

• Page/email clinician when alert is trigger 

Wait, I 

received a 

message! 

Feedback 

• Positive 

• Alerts were found to be accurate when compared against lab data 

• In-basket report allows for quick analysis of messages 

• Pass off note allows for more efficient follow up. 

• Negative 

• Messages are triggered to many times 

• No way to mark alerts as reviewed. 

Self Assessment 

• Once an alert is triggered where is the message sent? 

A. Pager 

B. In Basket 

C. A&B 

D. Outer space 

Questions? 

8/29/2012 

6

Meeting the PPMI Goals for 

Technology –“Is A Puzzlement” 


• Recognize the PPMI Goals related to 

barcoding 

• Identify methods of overcoming barriers to 

achieving barcode verification for medication 

administration 

• Identify methods of integrating barcode 

verification into compounding and 

preparation processes 

PPMI National Dashboard 

• Percentage of hospitals/health systems that 

routinely use machine readable coding (e.g., 

bar coding technology with or without a 

robot) in the inpatient pharmacy to verify 

doses during dispensing [C2j]. 

33.9% 

Barcoding to Achieve PPMI Goals 

Linda Fred, BS Pharm, MBA 

Director of Pharmacy and Anticoagulation Services 

Carle Hospital and Carle Physician Group 

Urbana, IL 

I have no conflicts of interest to report. 

PPMI Goals Related to Barcoding 

• C2j: Use of bar‐code technology during the 

inventory, preparation, compounding, and 

dispensing processes. 

• C2l: Use of bar‐code bar code technology during 

medication administration. 

PPMI National Dashboard 

• Percentage of hospitals/health systems that 

use machine‐readable coding (e.g., Bar‐Code 

Medication Administration [BCMA] system) to 

verify the identity of the patient and the 

accuracy of medication administration at the 

point‐of‐care [C2l]. 

50.2% 

8/29/2012 

1

Self‐Assessment Question 

Which of the following are PPMI Goals related to 

barcoding? 

A. Barcode verification at the time of 

medication administration. 

B. Use of barcode verification in inventory 

functions. 

C. Use of barcode verification during 

compounding. 

D. All of the above. 

Barcoding For Medication 

Administration 

• Goal: Barcode verification from manufacturer to 

patient 

• Software & Hardware Requirements: 

– Electronic medical record support 

– Integrated barcode validation 

– Mechanism for applying barcodes to all products 

– Strategically placed computers and scanners (bedside, 

pharmacy) 

– Repackaging equipment (or outsourced) 

Medi‐Dose Packaging Medical Packaging Inc 

Automed FastPak EXP 

Barriers: Barcode Verification During 

Medication Administration 

• Expense –EMR, Repackaging/Outsourcing 

• Barcode Variables: 

– Package size 

– Overwraps and outer packaging 

p p g g 

– Different types of barcodes (scanner programming) 

– EMR generated versus manufacturers’ barcode 

(repackaged products) 

• Compliance: setting expectations, sharing the data, 

troubleshooting issues 

8/29/2012 

2

Patient Scanning 

Compliance 

Sample Compliance Report 

Medication Scanning 

Compliance 

Total 

Administrations 

# of Admins With 

Patient Not Scanned 


Medication Not 

Scanned 


Neither Medication 

Nor Patient Scanned 

96.97% 96.97% 33 1 1 1 

100.00% 100.00% 5 

99.42% 99.42% 172 1 1 1 

91.67% 91.67% 36 3 3 3 

100.00% 0.00% 1 1 

100.00% 100.00% 7 

Integration of Barcoding into 

Compounding 

• TPN and batch compounding capability 

• Scanning during patient specific compounding 

• Fully automated IV compounding 

• Robotic Chemo compounding 

Self‐Assessment Question 

Barcoding for medication administration 

requires: 

A. Hardware and software support 

B. A clearly l l communicated i dcompliance li plan l 

C. Packaging plans that ensure a scannable bar 

code on every product 


Baxa Exactamix 1200 

Epic Dispense Preparation Baxa Intellifill IV 

8/29/2012 

3

Cytocare Self‐Assessment Question 

References 

• Medical Packaging Inc: 

http://www.medpak.com/v1/Main/Default.as 

px?expand=Home 

• Amerisource Bergen g Drug g Corporation p Web 

Site – FastPak EXP: 

http://www.amerisourcebergen.com/abcdrug 

/PDFs/Global/FastPakEXP_12_09.pdf Baxa 

DoseEdge Web Site: 

http://www.baxa.com/doseedge/ 

Technology options for integrating barcoding 

into compounding range from batch/TPN 

compounders to fully automated IV 

preparation systems. systems 

A. True 

B. False 

References 

• The Consensus of the Pharmacy Practice Model 

Initiative. Am J Health‐Syst Pharm. 2011; 68:1148‐52. 

http://www.ajhp.org/content/68/12/1148.full.pdf+h 

tml 

• Pharmacy Practice Model Initiative and the PPMI 

National Dashboard. 

http://www.ashpmedia.org/ppmi/docs/ppmi_nation 

al_dashboard.pdf 

• MediDose Web Site: 

http://www.medidose.com/medidose.aspx 

References 

• Baxa em1200 Web Site: 

http://www.baxa.com/PharmacyProducts/Aut 

omatedCompoundingDevices/ProductDetail/? 

id=2CA80FF5‐A21F‐9E08‐20BC7D50A42B557A 

• Baxa/For Health Technologies Web Site: 

http://www.fhtinc.com/benefits.html 

• Health Robotics Cytocare Web Site: 

http://www.health‐ 

robotics.com/en/solutions/cyto‐care/ 

8/29/2012 

4

Meeting the PPMI Goals for Technology – 

“Is a Puzzlement” 

PPMI & “Ideal” Work Queue 

Corrie Vasilopoulos, Pharm.D., BCPS 

Clinical Manager 

NorthShore University Health System – Glenbrook 

Hospital, Glenview, IL 

** I have no disclosures. ** 

Get to Know You… 

• Show of Hands…. 

• How many have electronic medical records 

system? 

• Currently l use real l time i clinical li i l monitoring i i 

system to support pharmacists as clinical 

medication managers? 

Self Assessment Question 

• Which of the following supports pharmacists 

as clinical medication managers? 

a. Systems supporting hands on oversight of 

distribution systems 

b. Operational systems driven by product 

distribution 

c. Decision support systems containing order entry 

alerts 

d. Decision support systems that provide a 

prioritized work queue 


• Recognize PPMI goals related to technology 

that support optimal pharmacy practice 

models 

• Identify methods for implementing 

technologies to support pharmacists as clinical 

medication managers 

• PPMI – Technology 

• NorthShore 

• “Ideal” Work Queue 

• Global Immunization 

• Ideal Transitions 

Overview 

PPMI – Technology Opportunities 1 

• Pharmacists as clinical medication managers 

• EMR – standardized format 

• Operational systems that drive behavior around 

clinical care 

• Decision‐support systems that maintain appropriate 

context 

– Real‐time, continuous monitoring 

– Prompts only appropriate users 

– Queues interventions by priority 

– Supports documentation 

Siska MH , Tribble DA. AJHP. 2011; 68:1116-1126. 

8/29/2012 

1

PPMI – Technology Solutions 2 

• Order management and review around drug 

therapy management services 

• Real time monitoring systems 

• Work k queue supporting i ddrug therapy h 

management and documentation 

• Automated notification of labs/ tests outside 

of normal range 

AJHP Vol 68, June 15 2011. 

NorthShore University Health System 

• Four Community Teaching Hospitals 

– Evanston, 354 beds 

– Glenbrook, 169 beds 

– Highland Park, Park 149 beds 

– Skokie, 195 beds 

• Medical Group, Research Institute, Foundation 

• Fully automated electronic medical records 

(EMR) system 

NorthShore –Work Queue Build 

•Front line 

clinical 

pharmacists h i t 

•Primary 

literature 

Scoring system 

recommendations 

Corporate clinical 

decision support 

committee 

•Pharmacy 

clinical 

services 

committee 

•Develop 

working rules 

• Prioritization 

• Safety 

• Quality 

•Regulatory 

• Financial 

EMR build, testing, 

education 

PPMI – Technology 

Recommendations 2 

• C7. EMRs designed to align pharmacists’ 

documentation outlining care provided and a 

method to ensure the quality of care provided 

• C9 C9. Technology T h l ddesigned i dtto ddemonstrate t t the th impact i t 

of pharmacy services on patient outcomes 

• C10. Technology designed to support pharmacy 

processes to improve patient outcomes 

AJHP Vol 68, June 15 2011. 

NorthShore –Work Queue 

• Clinical surveillance system internal to EMR 

• Scoring system based on changing clinical 

status and documentation 

• Notification ifi i for f patients i requiring ii review i and d 

possible intervention 

• Supports pharmacist documentation 

• Developed & maintained by informatics 

personnel 

Self Assessment Questions 

• Building an ideal work queue integrated 

within a health system’s EMR can be achieved 

with pharmacy informatics specialists 

– True 

– False 

8/29/2012 

2

Global Immunizations 3 

• Jan 2012: CMS and The Joint Commission 

require healthcare organizations to publicly 

report immunization compliance rates 

– IMM‐1a Pneumococcal Immunization – Overall rate 

– IMM‐1b Pneumococcal Immunization –Age 65 and 

Older 

– IMM‐1c Pneumococcal Immunization –High Risk 

Populations (Age 6 through 64 years) 

– IMM‐2 Influenza Immunization 

http://www.jointcommission.org/core_measure_sets.aspx 

Pneumococcal Vaccine Work‐Flow 

• Nurse completes initial assessment, including 

vaccine history 

• Clinical decision support based on patient 

problem list list, vaccine history history, and allergies 

• Point flags to pharmacist for patients requiring 

vaccination (work queue) 

• Pharmacists place order for vaccine and 

documentation per protocol 

Ideal Transitions 

• Targeted care by multidisciplinary team for 

patients at high risk for re‐admission 

• “High Risk List” generated daily based on 

variables within EMR 

– Currently list emailed to pharmacists (limitation of 

system) 

• EMR contains diagnosis‐specific patient lists 

(ex. myocardial infarction, heart failure) 

Vaccination at NorthShore 

• Nursing responsible for influenza vaccination 

program 

– Clinical decision support in EMR 

• Pneumococcal vaccination program 

– Pediatricians to order for 6‐18 years old 

– Pharmacists accountable for all adult patients 

Ideal Transitions ‐ High Risk 

• Evaluation of current status at NorthShore 

– Patients readmitted within 30 days 

• Multidisciplinary team identified variables for 

re re‐admission admission risk (evidence based) 

– Co‐morbidities, labs, # meds, encounters 

– Statistical analysis using simple regression model 

• Developed model engineered to our patient 

population 

Ideal Transitions 

• Unit‐based pharmacists utilize “high risk” list 

and diagnosis‐specific lists to screen patients 

for targeted education 

• Medication education consult order placed 

• Medication education consult order placed 

• Patient education by pharmacist using teach 

back method 

• Documentation to next care provider 

– Information taught, further need, goals 

8/29/2012 

3

Challenges 

• Clinical surveillance tool 

– Resources, education, culture 

• Ideal transitions 

– IIntegration i of f clinical li i l decision d i i support tool l into i 

EMR (currently emailed) 

– Documentation to next care provider 

• Management of medication preparation and 

distribution 

Corrie Vasilopoulos, Pharm.D., BCPS 

cvasilopoulos@northshore.org 

References 

1. Siska MH , Tribble DA. Opportunities and challenges related 

to technology in supporting optimal pharmacy practice 

models in hospitals and health systems AJHP. 2011; 68:1116‐ 

1126. 

22. The Consensus of the Pharmacy Practice Model Initiative. Initiative 


http://www.ajhp.org/content/68/12/1148.full.pdf+html 

3. The Joint Commission Core Measures Set. Available at: 

http://www.jointcommission.org/core_measure_sets.aspx. 


8/29/2012 

4

Mobile Devices: Beyond Angry Birds 

Don’t Worry Be Appy 

Adam Bursua, PharmD, BCPS 


College of Pharmacy 

UUniversity i it of f Illinois Illi i at t Chi Chicago 

The speaker has no conflicts to disclose. 

Goals 

• Compare and contrast characteristics of Apple 

and Android mobile applications 

• Identify traditional hard copy and electronic 

references with mobile application pp versions 

• List useful pharmacy focused mobile apps 

• Describe popular mobile applications with 

medical specialty concentrations 

• Describe Dropbox and Goodreader 

functionality 

Agenda 

• Apple vs Android 

– Walkthrough of App store and intro to Google Play 

• General Mobile App Reference Products 

– HHard dcopy references f gone mobile bil 

– Electronic references and “app only” software 

• Specialty Mobile Apps 

• Productivity Apps for Healthcare Professionals 

8/29/2012 

1

A Brief Personal History 

• 1984 – Commodore 64 computer 

• 1991 –1 st Windows PC 

• 1996 –Sent first e‐mail 

• 2004 –Palm Treo 

• 2008 – 1 st android smartphone G1 

• 2010 –G2 phone and Mac Desktop 

• 2011 ‐ 2 nd gen Ipad 

• 2012 –2 nd Child Born* 

*gadget purchases require prior 

authorization � 

Apple 

• Initial innovators 

• Uses i‐tunes and mobile 

“App Store” 

• Apple controls app design 

– Apps w/ more polished feel 

• I‐phones and I‐pads 

– Limited hardware selection 

– No devices w/ tactile keypad 

– Some Apps may have 

different interface for iphone 

and ipad* 

I‐Apps vs Android 

Apple App Store 

Walkthrough 

• Featured Apps 

– New 

– Whats hot 

– Genius 

• Categories 

– 22 total 

– Health and Fitness and 

Medical 

• Top 25 

– Sorts by paid vs free 

– Ranks by popularity 

• Search and Updates 

Google (Android) 

• Successful copycats 

• Uses Google “Play Store” 

– Orig. Android Marketplace 

• Android is “open source” 

– Anyone can submit an app 

• Many phones and tablets 

– Something for everyone 

– Apps primarily designed for 

smartphone vs tablet users 

8/29/2012 

2

Google Play 

• Google Play 

– Interface to purchase multiple 

media products 

• Music, movies, books, apps, etc. 

• App store within Google Play 

– Interface varies depending on 

service provider and operating 

system 

• Featured 

– Staff picks, games, editor’s 

choice 

• Top Selling 


APPS! 

General Pharmacy/Medical 

Reference Apps 

• Mobile versions of hard copy references 

– Facts and Comparisons ‐ PDR 

– AHFS ‐ Pharmacist’s Letter* 

Many more 

– Many more 

• Mobile versions of electronic references 

– Micromedex* ‐ Lexi‐Comp 

– Up‐To‐Date* ‐ Epocrates 

– Medscape 

8/29/2012 

3

Pharmacy Specialty Apps 

• Generics (apple) 

– Searchable database of generics 

• iPharmacy 

– Useful pill p Identifier included 

• IV Compatibilty 

– Trissel’s database 

• Iwarfarin (apple) 

– Incorporates warfarin pharmacogenomics based 

on VKOR and CYP2C19 

Specialty Focused Apps 

• Cardiovascular • Critical Care 

– ACC ACLS guides – ICU Trials 

– Digoxin dose calculator • Pulmonary 

• IInfectious f ti Di Diseases – AAnesthesiologist h i l i app 

– Johns Hopkins Guide – Asthma tracker 

iphone or Ipad • Preventive Care 

– Sanford guide 

– Vancomycin calculator 

– AHRQ 

Specialty Focused Apps 

• Hepatology 

– MELD score calculator 

• Endocrine 

• Oncology 

– InPractice Oncology 

– Chemo Calc 

– Endocrinology d i l and d • Pd Peds 

Endo Emergency – Pedi Quick Calc 

• Renal 

• Calculator Suites 

– BS3 Nephrology pack – Mediquation 

– Calculate by QxMD 

8/29/2012 

4

Other Useful Productivity Apps 

• Dropbox 

– Stores your data in “The Cloud” 

– Share files across devices 

– Share selected folders with collaborators, 

collaborators 

students, residents, family, etc. 

• Reader applications (eg., Goodreader) 

– Manages your pdfs, ppts, docs, etc. 

– Allows annotation, sharing, syncing w/ “cloud” 

Questions & Audience Input 

Questions & Audience Input 

Post Test Question 1 

1. Which of following “hard copy” references 

has a mobile “App” version? 

a. AHFS Drug Information 

b h h i i ’ k f ( ) 

b. The Physician’s Desk Reference (PDR) 

c. The Pharmacist’s Letter 

d. All of the above 

8/29/2012 

5


2. Which of the following is true regarding mobile 

applications for smartphones? 

a. Mobile “Apps” for android devices can be obtained 

through “Google Play”. 

b. Android “Apps” are open‐source, while Apple 

retains design controls over “Apps” for the Iphone 

and Ipad. 

c. “Apps” for the Iphone must be downloaded to a 

computer before being transferred to the device 

d. Both A and B 

• 


3. Which of the following mobile “Apps” allows 

users to save files in “the cloud” so that they 

can be accessed from connected computers, 

smartphones smartphones, and other devices? 

a. Dropbox 

b. SaveAcross 

c. Mobile PDR 

d. GoodReader 

8/29/2012 

6

Mobile Devices: Beyond Angry 

Birds 

David Tjhio, Pharm.D. 

Healthcare Executive 

Cerner Corporation 


• Identify the mobile device hardware and 

software options currently available 

• Describe applications and uses of mobile 

devices in the clinical setting 

• List the software options available on each 

software platform 

Image source: hammer.net 

HARDWARE 

Disclosures 

• My spouse and I are shareholders in: 

– Apple Inc. 

– Google Inc. 

• CConflicts fli t were resolved l dth through h peer review i 

Additional Learning Objectives 

• Describe the current trends in iOS vs. Android 

penetration in the U.S. 

• Compare and contrast the available app 

options in different productivity categories 

• Identify key accessories for use with mobile 

devices 

Phones/Handheld Devices 

• Phones 

– iPhone/iPod Touch 

– Android 

– Blackberry 

– Windows 

Image source: androidauthority.com 

8/29/2012 

1

Smartphone Penetration in the US 

• Tablets 

– iPad 

– Android 

• Amazon Kindle Fire 

• Google Nexus 

• Samsung Galaxy Tab 

Tablets 

Image sources: apple.com, amazon.com, notebookforums.com, technutty.co.uk 

iOS vs. Android Tablet Usage 

Liu R. iOS and Android tablet usage level, reveals study (June 18, 2012). Retrieved August 1, 2012, SlashGear website, http://www.slashgear.com/ios-andandroid-tablet-usage-level-reveals-study-18234449/#entrycontent 

Source: nielsen.com (2012) 

US Tablet Users 

Top 10 Mobile Devices 

Source: Good Technology (good.com, 2012) 

8/29/2012 

2

Net Activations by Industry 

Source: Good Technology (good.com, 2012) 

Number of Available Apps 

As of August 19, 2012 

Source: Mobilewalla.com 

• Games 

• Wine 

• Music 

• Travel 

• Food 

• Photography 

• GPS 

Fun Stuff 

Image source: cultofmac.com 

APPS 

Image source: internaldrive.com 

Monthly App Downloads 

Source: Xyologic.com, 2012 

Social Networking 

Features Integrated apps for access to Social Networking 

sites 

Platforms iOS, Android 

CCost t FFree 

Popular 

Examples 

•Facebook 

•Twitter 

•Google + 

•LinkedIn 

•TweetDeck 

•HootSuite 

8/29/2012 

3

Social Media Dashboard 

Notes 

Dictation 

Image sources: hootsuite.com, tweetdeck.com 

Image sources: evernote.com, pockeysoft.com, phatware.com 

Features Excellent voice recognition; can dictate text 

messages, e‐mails, tweets, and status updates 

Platforms/ 

Integration 

Cost Free 

Popular 

Examples 

iOS, Android 

•Dragon Dictation 

•Swype 

•Dictation (iPad 3) 

Notes 

Features Text conversion from handwriting; synched audio 

recording; remote note storage; easy sharing 

Platforms/ iOS, Android 

Integration 

CCost t F Free (basicversion) (b i i ) up t to $9.99 $9 99 (plus ( l additional dditi l 

costs for add‐ons) 

Popular 

Examples 

•Evernote 

•UPAD 

•WritePad 

•Notes Plus 

Notes 

Image source: notesplusapp.com 

Image source: swype.com 

8/29/2012 

4

News Readers/Aggregators 

Features Summary of news and stories; can “learn” your 

preferences 

Platforms/ iOS, Android 

Integration 

Cost Generally free 

Popular 

Examples 

•Flipboard 

•Zite 

•Currents 

•Pocket (Read 

It Later) 

•Instapaper 

Remote/Cloud Storage 

Features Easy access to stored files; initially free storage; 

version control for files; backup storage 


Cost Initially free, varying price tiers for paid storage 

Popular 

Examples 

•Dropbox 

•Google Drive 

•SugarSync 

•iCloud 

File Reader 

•SkyDrive 

Features Converts PDFs and other file formats for easy 

reading; supports highlighting and annotation 


Cost $4.99 (GoodReader); some free options 

Popular 

Examples 

•GoodReader (iOS only) 

•Adobe Reader 

News Readers/Aggregators 

Image sources: zite.com, google.com, flipboard.com 

Cloud Storage Comparison 

Source: Ars Technica (arstechnica.com, April 26, 2012) 

Source: www.goodreader.net 

GoodReader 

8/29/2012 

5

Remote Control/Remote Access 

Features Screen sharing; remote access 


Cost Generally free for personal use 

Popular 

Examples 

•TeamViewer 

•Splashtop 

•LogMeIn 

•Screenleap 

Voice Over Internet Protocol 

iWork 

Image source: iphonelah.com 

Image source: apple.com 

Voice Over Internet Protocol 

Features Free voice and/or video calls; free instant/SMS 

messaging; free international calling 


Cost Free 

Popular 

Examples 

•Skype 

•iCall 

•Google Voice 

•TruPhone 

Office Apps 

•Viber 

•Line2 

Features File editing for Office files; syncs with cloud services 


Cost Free to $20 

Popular 

Examples 

•Keynote 

•Numbers 

•Pages 

• Keyboard 

• Stylus 

• Projector cables 

• HDMI cables 

• Apple TV 

•Google Docs 

•Quickoffice 

•Office 2 HD 

Accessories 

•Documents to 

Go 

8/29/2012 

6

Contact Information 

• E‐mail: 

– david.tjhio@cerner.com 

• Twitter: 

– @jh10 @tjh10 

– @tjh10_HCIT 

• LinkedIn: 

– http://www.linkedin.com/in/davidtjhio 


2. As of August 2012, how many apps have been 

developed across the four major platforms 

(Apple, Android, Blackberry, Windows)? 

aa. Over 1,000,000 1 000 000 

b. 900,000 

c. 800,000 

d. 700,000 


4. Which of the following statements is true 

regarding Cloud Storage offerings? 

a. All Cloud Storage companies offer the same 

amount of free storage 

b. All Cloud Storage companies charge the same 

amount for paid storage 

c. All Cloud Storage companies offer some amount 

of free storage 

d. All Cloud Storage companies have a maximum 

file size 


1. What percentage of the US Smartphone 

market is made up of Android OS phones and 

Apple iPhones? 

aa. 55% 

b. 65% 

c. 75% 

d. 85% 


3. Which of the following is a feature that is 

currently available in one of the Notes apps 

described in the presentation? 

aa. Dictation 

b. Text conversion from handwriting 

c. Screen sharing 

d. News aggregation 

8/29/2012 

7

Guideline Updates for Common 

Infections in Neonates and Children 

Lisa Lubsch, PharmD, AE‐C 

Southern Illinois University Edwardsville 

School of Pharmacy 


Objectives for Technicians 

• List the antibiotics used for treating early‐ 

onset sepsis in neonates, UTIs in infants and 

young children, and CAP in infants and 

children. 

• Describe how to calculate the regimen 

(including dose and frequency) for the 

recommended parenteral antibiotic 

prescribed for a neonate with sepsis or a child 

with a UTI or CAP. 

Question 1 

• EW is a 2 day old male with fever and 

decreased PO intake. What is the most likely 

pathogen causing fever in EW? 

AA. Group B streptococci (GBS) 

B. Escherichia coli 

C. Listeria monocytogenes 

D. Herpes simplex virus 

Objectives for Pharmacists 

• Review the latest recommendations for management 

of early‐onset sepsis in neonates, urinary tract 

infections (UTIs) in infants and young children, and 

community‐acquired pneumonia (CAP) in infants and 

children. 

• Sl Select tappropriate it empiric ii antibiotic tibi ti therapy th for f a 

neonate with sepsis or a child with a UTI or CAP. 

• Recommend transition from parenteral to oral 

antibiotic therapy for a child with a UTI or CAP when 

appropriate. 

• Indicate the appropriate duration of antibiotic therapy 

for a neonate with sepsis or a child with a UTI or CAP. 

Pediatrics 2012;129:1006–15 

Early Onset Sepsis 

• Suspected sepsis, septic work‐up (SWU), rule‐ 

out sepsis 

• Onset ≤ 3 days 

• Risk ikf factors 

– Preterm birth / low birth weight 

– Chorioamnionitis (maternal fever / leukocytosis) 

– Premature rupture of membranes (> 18 hours) 

– Maternal colonization with GBS 

8/29/2012 

1

Early‐Onset Sepsis 

• Sign and symptoms are nonspecific 

• Laboratory data 

– Neutrophil indices are useful, but vary 

– Peripheral i h lbl blood d culture l preferred f d 

– Lumbar puncture may be unnecessary 

– Urine culture is unnecessary 

– Tracheal aspirate culture with ET tube placement 

may be helpful 

– Others 

Question 2 

• What is the recommended gentamicin 

regimen for EW? 

A. 5 mg/kg q 36 hours 

BB. 5 mg/kg q 24 hours 

C. 4 mg/kg q 24 hours 

D. 2.5 mg/k q 12 hours 

Antibiotic Duration 

Laboratory data normal 

Duration 

48 hours 

Bacteremia without focus 10 days 

Meningitis from GBS ≥ 14 days 

Meningitis from Gram‐negative 

organisms 

≥ 21 days 

Early‐Onset Sepsis Treatment 

• Ampicillin + Aminoglycoside is preferred 

– Cefotaxime is alternative to AMG 

– Avoid Ceftriaxone 

Pediatrics 2006;117:67‐74 

Aminoglycoside Regimen 

• Extended interval versus traditional dosing 

– Based on gestational age, postnatal age and/or 

birth weight 

• Obtain peak and trough concentrations if 

treating longer than 48 hours 

– Peak 8 –12 mcg/ml 

– Trough < 1 mcg/ml 

Question 3 

• EW has negative blood and CSF cultures x 48 

hours. What is the most appropriate plan for 

EW’s antibiotics? 

AA. Discontinue Ampicillin and Gentamicin 

B. Continue Ampicillin and discontinue Gentamicin 

C. Continue Ampicillin and Gentamicin x 10 days 

D. Continue Ampicillin and Gentamicin x 14 days 

8/29/2012 

2

When Is An Antiviral Necessary? 

• Herpes simplex virus type 2 

• Risk factors 

– Maternal infection, especially during 3 rd trimester 

• Categorized as skin, eye, mouth (SEM) disease, 

CNS disease, or disseminated disease 

• Acyclovir 20 mg/kg IV q 8 hours, duration 

depends on diagnosis 

Question 4 

• BR is a 18 month old female with fever and 

decreased PO intake. What is the most 

common pathogen causing fever in BR? 

AA. Coagulase Coagulase‐negative negative staphylococci 

B. Lactobacillus spp 

C. Enterobacter cloacae 

D. Escherichia coli 

Urinary Tract Infection 

• Sign and symptoms are 

nonspecific 


– Urinalysis 

– Urine culture with > 50,000 

CFUs / mL by urethral 

catheterization or 

suprapubic aspiration 

– Renal and bladder 

ultrasonography within 2 

days 

– Voiding 

cystourethrography is 

unnecessary initially 

Pediatrics 2011;128:595–610 

Urinary Tract Infection 

• Prevalence of 5%, lower in boys 

• Risk Factors 

Female Male* 

White race 

Nonblack race 

24 hours 

Absence of other sources 

*Uncircumcised increases rate 4‐20 x 

Urinary Tract Infection Management 

• PO = IV therapy 

• IV therapy x 24‐48 

hours if 

– Not tolerating oral intake 

– ‘Toxic’ appearance 

– Adherence issues 

• Adjust based on culture 

and sensitivity data 

• Duration 7‐14 days 

Parenteral Treatment 

Ceftriaxone 75 mg/kg q24h 

Cefotaxime 50 mg/kg q8h 

Gentamicin 2.5 mg/kg q8h 

SMX/TMP 

Oral Treatment 

3‐6mg/kg BID 

Cephalexin 25 mg/kg QID 

Cefixime 8 mg/kg daily 

8/29/2012 

3

• BR is on day 2 of 

cefotaxime with the 

following urine culture 

and sensitivity results. 

What is the preferred 

therapy for discharge? 

A. Amox/clav 

B. Cefixime 

C. SMX/TMP 

D. Nitrofurantoin 

Question 5 

Question 6 

• MY is a 6 year‐old male with fever and 

decreased PO intake. What is the most 

common pathogen causing fever in MY? 

AA. Streptococcus pneumoniae 

B. Haemophilus influenzae 

C. Mycoplasma pneumoniae 

D. Influenza virus 

Community Acquired Pneumonia 

• Respiratory distress 

• Pulse oximetry measurement < 90% on room air 


– Posteroanterior and lateral CXR 

– CBC if severe 

– Acute‐phase reactants may be useful 

– Rapid viral testing during seasons 

– M. pneumoniae testing if suspicious 

– Blood culture if moderate to severe or complicated 

– Respiratory culture in sputum producers 

– Tracheal aspirate culture with ET tube placement 

– Urinary antigen testing is not recommended 

Clinical Infectious Diseases 2011;53: e25‐76 


• Simple versus complicated 

• Predisposing conditions 

– Bronchopulmonary 

Dysplasia 

– Gastroesophageal Reflux 

– Aspiration 

– Asthma 

– Sickle Cell 

– Cystic Fibrosis 

– Immunodeficiency 

– Neuromuscular Disease 


Treatment 

Setting Recommended Treatment 

Outpatient Amoxicillin 90 mg/kg/day div BID x 10 days 

± Azithromycin 10 mg/kg on day 1, then 5 mg/kg daily on 

days 2–5 

± Oseltamivir 

Inpatient‐ i Ampicillin i illi 200 mg/kg/day /k /d di div q6h h 

immunized ± Azithromycin 10 mg/kg on days 1 and 2 

± Vancomycin or clindamycin for CA‐MRSA 


Inpatient‐ not Ceftriaxone 50‐100 mg/kg/day q 12‐24h or cefotaxime 150 

fully mg/kg/day div q8h 

immunized ± Azithromycin 10 mg/kg on days 1 and 2 

± Vancomycin or clindamycin for CA‐MRSA 


8/29/2012 

4

Question 7 

• MY’s CXR reveals a lobar pneumonia. What is 

the recommended therapy for MY? 

A. Ampicillin 

BB. Ampicillin + Azithromycin 

C. Ceftriaxone + Azithromycin 

D. Vancomycin 

Guideline Updates for Common 

Infections in Neonates and Children 

Lisa Lubsch, PharmD, AE‐C 

Southern Illinois University Edwardsville 

School of Pharmacy 

Summary 

Infection Etiology Treatment 

Early onset sepsis Group B 

streptococci 

ampicillin and 

gentamicin 

Urinary tract Escherichia coli 3 rd generation 

infection cephalosporin 

Community 

acquired 

pneumonia 

Streptococcus 

pneumoniae 

ampicillin IV or 

amoxicillin PO 

8/29/2012 

5

Immunizations: The Superheroes 

to Protect Against g Disease 

Vallery Huston, PharmD 

Objectives 

• Pharmacists 

– Discuss why it is important for pharmacists to provide immunizations 

– Review the legal requirements for pharmacists to provide immunizations in 

the state of Illinois 

– Discuss how to interpret the 2012 Immunization Schedules for children, 

adolescents, and adults 

– Describe how to incorporate discussions regarding immunizations as a part of 

the routine patient interaction 

• Technicians 

– Discuss why it is important to provide immunizations for patients. 

– Explain the legal requirements for providing immunizations in the state of 

Illinois. 

– Describe the 2012 Immunization Schedules for children, adolescents, and 

adults. 

– Describe how to collect immunization information as a part of the patient 

interaction. 

Influenza and Pneumococcal Disease 

Impact 

• Estimated 200,000 hospitalizations per year in 

the United States 

• 8 th leading cause of death in the United States 

in 2009 

• 53,582 deaths in 2009 

1. Kenneth D. Kochanek, M.A.; Jiaquan Xu, M.D.; et al Centers for Disease Control Division of Vital 

Statistics. Deaths: Preliminary Data for 2009 

Conflict of Interest 

• I have no actual or potential conflict of 

interest in relation to this activity. 

Importance of Vaccines 

Vaccination Rates for 2011 

Influenza Vaccination Rates for 2011 

Age 65 and over 64.3% 

Age 50‐65 43.8% 

Age 88‐49 49 27 27.5% 5% 

• The percentage of adults aged 65 and over who had 

ever received a pneumococcal vaccination increased 

from 42.4% in 1997 to 62.3% in 2011. 

2. Centers for Diseas Control. CDC/NCHS, National Health Interview Survey, 1997–2011. 

Available at: http://www.cdc.gov/nchs/nhis.htm/. 

8/29/2012 

1

Health care provider vaccination rates 

• Only 52.9% of Health Care Providers received 

influenza vaccine in 2009 

• Consider making influenza vaccination 

mandatory for health system 

3. National Health Interview Survey 2009. 

Legal Requirements 

• Technicians May Not administer vaccinations 

– May manage inventory 

– Help process paperwork 

• St Student d t Ph Pharmacists i t 

– May administer vaccinations under the 

supervision of a pharmacist 

– Must have all legal requirements for vaccination 

completed 

Current ACIP Recommendations 

4. Centers for Disease Control. ACIP Recommendations. Available at. http://www.cdc.gov/vaccines/recs/ACIP/ 

Legal requirements 

• To administer Vaccines in Illinois a pharmacist 

must: 

– Have an active Illinois Pharmacist License 

– Complete a vaccine delivery education program 

– Have active CPR training 

– Complete OSHA training yearly 

– May administer per protocol or per order 

What are the current recommendations for 

a one time dose of Tdap vaccine? 

1. All patients 7‐10 

years of age 

2. All patients 10‐64 

years of age 

3. All patients >65 

years of age 

4. All patients >11 

years of age 


4. Centers for Disease Control. ACIP Recommendations. Available at. http://www.cdc.gov/vaccines/recs/ACIP/ 

8/29/2012 

2


Influenza Vaccine 

• 2012‐2013 Strains 

– A/California/7/2009 (H1N1)(Change from 2011‐ 

2012) 

– A/Victoria/361/2011 (H3N2)(same as 2011‐2012) 2011 2012) 

– B/Wisconsin/1/2010 (same as 2011‐2012) 

• No vaccine shortage 

5. Centers for Disease Control. Influenza. Available at: http://www.cdc.gov/flu/about/season/flu-season-2012-2013 

Pneumococcal Vaccine 

• Pneumococcal 23‐valent polysaccharide vaccine: Pneumovax® 

– Indicated in patients >50 years of age or older 

– Indicated for patients >2 years who are at increased risk for 

pneumococcal disease. 

• Chronic disease 

• New indication for smoking and asthma 

• Pneumococcal 13‐valent conjugate vaccine: Prevnar® 

– New indicated for adults >50 years of age 

– Indicated for children aged 6mo –5years 

• Previous PCV vaccine 7‐valent 

• Covers 4 more serotypes of pneumococcal disease than previous PCV 

8. Pneumovax Vaccine. [Prescribing Information] Whitehouse Station, NJ. Merck and Co, Inc; 2011. 

9. Prevnar Vaccine. [Prescribing Information] Philadelphia, PA. Pfizer Inc. 2011. 

New Vaccine information 

• Influenza 

• Pneumococcal 

• Pertussis ‐ Tdap 

• Shingles 

• Human Papillomavirus (HPV) vaccine 

New Influenza Delivery 

• High dose flu vaccine 

– Frail elderly 

– > 65 years of age 

– Same strains as TIV 

– Higher antibody levels 

• Intradermal Flu Vaccine 

– Adults 18‐64 years of age 

– Preservative Free 

– 0.1 ml 

6. Centers for Disease Control: Influenza. Available at: http://www.cdc.gov/influenza. 

7. Fluzone Intradermal vaccine [Prescribing Information]. Swiftwater, PA: Sanofi Pasteur Inc.; 2011. 

Pneumovax® vs. Prevnar® 

• Clinical Debate 

• Pneumovax® 

– Covers 23 serotypes 

d i ifi b ff 

– Does not produce a significant booster effect 

• Prevnar® 

– Covers 13 serotypes 

– Elicits a greater immune response 

– Produces a booster effect 

8/29/2012 

3

The number of pertussis cases in the 

United States in 2010 was…. 

1. More than the 

number of cases in 

2000 

2. Less than the 

number of cases in 

2000 

3. Is about the same 

as it was in 2000 

4. Zero 

CDC Pertussis Data 

12. Centers for Disease Control and Prevention. Pertussis. Available at: http://www.cdc.gov/pertussis/images/pertussisgraph-2012-lg.jpg 

Tdap vaccination rates 

• Great opportunity for pharmacists to impact disease 

transmission 

• Percent of patients who have received Tdap in past 2 years 

– Total Tdap 2.1% 

• Whites 1.7% 

• Blacks 3.9% 

• Hispanics 1.8% 

• What are your hospitals Tdap vaccination rates? 

13. Centers for Disease Control and Prevention. Vaccine stats. Available at: 

http://www.cdc.gov/vaccines/stats-surv/nis/downloads/nis-adult-summer-2007.pdf 

Tdap – Pertussis Vaccine 

• Pertussis outbreaks across the country 

– 7,867 cases in 2000 

– 27,550 cases in 2010 

– Significant increase in pertussis 

• Possible causes 

– Decreased vaccination rates 

– Decrease in heard immunity 

– Adults as carriers 

10. Centers for Disease Control. MMWR. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5104a1.htm 

11. Centers for Disease Control. Pertussis. Available at: http://www.cdc.gov/pertussis/outbreaks.html 

Tdap‐Tetanus, diphtheria, pertussis 

• Secondary to significant pertussis outbreaks 

ACIP now recommends 

– Patients received one booster dose of pertussis 

containing vaccine 

– Booster dose for adults and adolescents over the 

age of 65 

– Recommended for all patients regardless of last 

tetanus booster 

Herpes Zoster/Shingles Vaccine 

• Available in 2006 

• Live vaccine 

• Vaccine decreases post herpetic neuralgia by 

6 67% % 

14. Zostavax Vaccine. [Prescribing Information] Whitehouse Station, NJ. Merck and Co, Inc.; 

2011. 

8/29/2012 

4

Herpes Zoster Vaccine 

Recommendations 

• FDA recently approved the vaccine for adults 

age 50‐59 

• ACIP has not changed recommendation for 

adults. Still recommend for adults over the 

age of 60. 

• Pharmacists who administer under protocol 

should not administer shingles vaccine to 

patient between 50 and 59 with out order 

from physician 

Zoster Vaccine and Pneumovax® 

• ACIP has not changed recommendations 

• Should not be administered simultaneously. 

– Simultaneous administration decreases varicella 

zoster antibody level post vaccine administration 

– Manufacturer recommends not administering the 

vaccine simultaneously and should be separated 

by 4 weeks. 

Why did the recommendation change? 

• Boys and Men can be HPV carriers and 

transmit virus without having active infection 

• Men can acquire anal warts and can be at an 

increased risk of anal cancer secondary to HPV 

infection. 

Hepres Zoster and Pneumovax® 

Should be administered how. 

1. Simultaneously, they 

have synergistic effects 

2. Separated, the 

pneumococcal 

antibody is lowered 

3. Separated, the zoster 

antibody is lowered 

4. Simultaneously, they 

do not effect antibody 

levels 

Human Papillomavirus (HPV) Vaccine 

• Previous Recommendations 

– All girls aged 11 –26 

• NNew Recommendations 

R d ti 

– All girls aged 11 –26 

– Boys aged 11 –26 

What can Pharmacists do? 

• Act as an advocate 

• Maintain inventory 

• Stay up to date 

• Get involved 

8/29/2012 

5

Pharmacists as Vaccine Advocate 

• Educate 

– Educate health care providers of importance of 

preventing transmission 

– Add vaccinations to medication reconciliation 

process for pharmacists and technitians 

• Vaccinate 

– Get certified to administer vaccinations 

– Work with physician to develop protocol 

– Increase vaccination rates at health system 

What is the “Pink Book” 

1. CDC textbook on 

epidemiology of 

vaccine preventable 

diseases 

2. ACIP book published 

yearly with vaccine 


3. Autobiography written 

by the pink panther 

Get Involved 

• Hospital Committee 

• Champion pharmacists as vaccine advocates 

and administrators. 

Maintain Vaccine Inventory 

• Pharmacy Staff 

– Know what vaccines should be administered to 

patients when they are hospitalized 

– Verify adequate levels of vaccine are in stock 

– Always handle and store vaccine appropriately 

• All staff should be aware of how to handle and store 

vaccine inventory 

• Staff should also be aware of how to handle vaccine 

that has been outside of recommended storage 

conditions 

Stay up to Date 

• Vaccine Recommendations change yearly 

• Vaccine resources 

– CDC.gov 

– Immunize.org 

– Pink Book: Epidemiology and Prevention of Vaccine‐ Vaccine 

Preventable Diseases (available online) 

– MMWR (Morbidity and Mortality Weekly Report) 

• Listserves 

– Immunization Action coaition (IAC): 

express@immunize.org 

– MMWR: www.cdc.gov/mmwr 

• Smartphone app: Shots 2012 

Questions? 

8/29/2012 

6

Assessment Questions 

1. What are the legal requirements a pharmacist 

must have/complete to administer 

vaccinations? 

A. Have an active Illinois Pharmacist License 

B. Complete a vaccine delivery education 

program 

C. Have active CPR training 

D. Complete OSHA training yearly 


• 

3. What are the current recommendations for 

Tdap vaccination regardless of their last 

Tetanus booster? 

A. Patients > 11years of age without 

contraindication 

B. Patients aged 10‐64 years of age 

C. Patients 7‐ 10 years of age 

D. Patients > 65 years of age 

5. Which of the following is true regarding 

simultaneous administration of pneumovax and 

shingles vaccine? 

A. They should be administered simultaneously, they 

have synergistic effects 

B. Administration of the two vaccines should be 

separated, the pneumococcal antibody is lowered 

C. Administration of the two vaccines should be 

separated, the zoster antibody is lowered 

D. They can be administered simultaneously. 

Simultaneous administration does not effect 

antibody levels 

2. Who may legally administer vaccinations in 

the state of Illinois with proper training and 

documentation? 

A. Pharmacists Only 

B. Pharmacists and Technicians 

C. Pharmacists and Pharmacy Students 

D. Pharmacists, Pharmacy Students and 

Pharmacy Technicians 

4. Who should receive high dose flu vaccine? 

A. Frail Elderly >65 years of age 

B. Patient < 65 years of age with diabetes 

C. Patients with chronic lung disease 

D. Adolescents age 5 – 11 years of age 

8/29/2012 

7

30 Years of HIV: 

An Update on Treatment Guidelines and Beyond 

Blake Max, PharmD, AAHIVE 

Clinical Associate Professor 

University of Illinois at Chicago College of Pharmacy 

HIV Clinical Pharmacist 

Ruth M. Rothstein CORE Center, Cook County Health and Hospitals System 

Pharmacist Objectives 

‐Describe recent revisions to the Department of Health and 

Human Services (DHHS) Guidelines for treatment of HIV‐1 

infected adults. 

‐Review first line antiretroviral regimens recommended by 

DHHS Treatment Guidelines. 

‐Compare and contrast recently approved antiretrovirals 

and those in development to first line antiretroviral agents. 

‐Recognize clinically significant drug interactions specific to 

antiretroviral therapy. 

Epidemiology 

Conflict of Interest Declaration 

• Speaker and Spouse are Stockholders: Pfizer, GSK, Merck 

• Spouse is an employee of GSK 

Any conflicts were resolved through peer review. 

Pharmacy Technician Objectives 

‐Identify DHHS Guidelines recommended antiretrovirals by 

brand and generic name. 

‐Recognize recommended initial combination regimens for 

HIV treatment treatment‐naïve naïve adults. adults 

‐Identify laboratory markers used to initiate and monitor 

antiretroviral therapy. 

‐Recognize side effects of antiretrovirals recommended for 

HIV treatment‐naïve adults. 

In the beginning… 

• 1981 

‐ Ronald Reagan is president 

‐ Avg pharmacists salary salary ≈ $35,000/yr 

‐ June 5 th ‐ MMWR describes the unusual occurrence 

of Pneumocystis carinii pneumonia (PCP) in 5 

otherwise th i healthy, h lth C Caucasian i MSM. MSM 

• 1982 

‐ CDC coins the term “AIDS” 

‐ 1600 cases/700 deaths 

• 1985 

‐ HIV confirmed as cause of AIDS 

8/30/2012 

1

HIV Linkage and Retention in Care 

Treatment Guidelines 

HIV and the Older Patient 

•Defined > 50 yo 

‐ Two groups: newly dx and those living with HIV/AIDS on ART 

‐ 30% of people living with HIV/AIDS > 50 

‐ Trend will increasingly include care for 60‐80 yo 

•Areas of concern between aging and HIV 

‐ Age related co‐morbidities complicates HIV tx 

‐ HIV may effect biology of aging 

‐ HIV screening remains low in this population 

2008 CDC survey only 35% adults (45‐64 years) had ever been 

tested for HIV despite 2006 CDC recommendation 

24 FDA Approved Antiretroviral Medications 

NRTI 

PI 

• Abacavir (Ziagen) • Atazanavir (Reyataz) 

• Didanosine (Videx) • Darunavir (Prezista) 

• Emtricitabine (Emtriva) • Fosamprenavir (Lexiva) 

• Lamivudine (Epivir) • Indinavir (Crixivan) 

• Stavudine (Zerit) • Lopinavir/r (Kaletra) 

• Tenofovir (Viread) 

• Nelfinavir (Viracept) 

• Zidovudine (Retrovir) • Ritonavir (Norvir) 

NNRTI 

• Saquinavir (Invirase) 

• Delavirdine (Rescriptor) • Tipranavir (Aptivus) 

• Efavirenz (Sustiva) •Fixed Fixed Dose Combination 

• Etravirine (Intelence) • Atripla (TDF/FTC/EFV) 

• Nevirapine (Viramune) 

• Truvada (TDF/FTC) 

• Rilpivirine (Edurant) • Epzicom (ABC/3TC) 

• Combivir (AZT/3TC) 

Integrase Inhibitor 

• Raltegravir (Isentress) 

Fusion Inhibitor 

• Enfuvirtide (Fuzeon) 

CCR5 Antagonist 

• Maraviroc ( (Selzentry) l ) 

•Complera Complera (TDF/FTC/RPV) 

• Trizivir (ABC/AZT/3TC) 

• Kaletra (LPV/RTV) 

What’s New in the Guidelines? 

‐DHHS Treatment Guidelines are updated every 6‐12 

months (March 2012, 240 page document) 

‐ HIV and the Older Patient 

‐ Treatment as HIV Prevention 

‐ Antiretroviral Drug Cost 

‐ Initiating ART in Tx‐naïve Patients 

‐ Drug Interactions 

HIV and the Older Patient 

Antiretroviral Therapy 

•Initiating ART regardless of CD4 count 

‐ Older patients have poorer immunological and clinical response 

to ART than younger patients. 

M ld HIV i di d l i di 

‐ Most older HIV+ patients are diagnosed late in disease 

‐ Choice of ART regimen(s) is not age specific, however can be 

affected by other co‐morbidities and medications. 

‐ Lack of information on long‐term safety, efficacy, changes in 

pharmacokinetics, and potential drug interactions. 

‐ Design of specific clinical trials to optimize ART in these patients 

8/30/2012 

2

Treatment for HIV Prevention 

•ART as Prevention 

‐ Rate of new infections in US has remained stable for past 4 years 

(~50,000/year) 

‐ HIV transmission is decreased with lower viral load 

‐ community viral load 

‐ HPTN 052 Trial: Marked decrease in transmission in 

discordant couples 

‐ PrEP (pre‐exposure prophylaxis) 

‐ Truvada recently FDA approved (July 2012) 

Trade‐Offs With Generics 

Advantages Disadvantages 

• Clear cost benefit • May involve change of regimen for 

patients who are on coformulated or 

single‐tablet regimens 

• Switch to the same drugs administered 

separately with generic substitutions 

• Possible problems with adherence 

Initial Regimen: 

Recommended/Preferred Agents 

EFV ATV/RTV 

TDF/FTC + 

DRV/RTV RAL 

ART Cost 

Antiretroviral Agent AWP Cost / month 

Atripla $2,081 

Complera $2,195 

Truvada $1,391 

Epzicom $1,119 $ , 

Atazanavir (Reyataz) $1,176 

Darunavir (Prezista) $1,230 

Raltegravir (Isentress) $1,171 

Ritonavir (Norvir) $308 (30 tabs) 

$617 (60 tabs) 

DHHS Recommended Initial Regimens 

Preferred Agents for First‐line Therapy 

NRTIs • Tenofovir/emtricitabine 

Plus a third agent 

NNRTI • Efavirenz 

Boosted PI • Atazanavir/ritonavir 

• Darunavir/ritonavir 

INSTI • Raltegravir 

Surrogate Markers 

•Efficacy of all antiretroviral clinical trials is based on: 

‐Clinical endpoints 

‐CD4+ T‐lymphocyte 

‐HIV viral load (copies/ml) 

8/30/2012 

3

DHHS Guidelines, March 2012: When to Start 

• Antiretroviral therapy recommended for all HIV‐infected pts; strength of 

recommendation varies according to CD4+ cell count or condition 

CD4+ Cell Count or Clinical Condition 

• CD4 + count < 350 cells/mm³ (AI) 

• CD4 + count 350‐500 cells/mm³ (AII) 

• CD4 + count > 500 cells/mm³ (BIII) 

________________________________________________________________ 

• History of AIDS‐defining illness (AI) 

• Pregnancy (AI) 

• HIV‐associated nephropathy (AII) 

• HBV coinfection (AII) 

• Patients at risk of transmitting HIV to sexual partners (AI, heterosexuals; AIII, 

others) 

• HCV coinfection (BII) 

• Patients > 50 years of age (BIII) 

NRTI “Backbone” 

Nucleoside Reverse Transcriptase Inhibitors 

Truvada > Epzicom p > Combivir 

Tenofovir Adverse Effects 

• Nephrotoxicity 

‐ Vitamin D deficiency, metabolic bone disease 

‐ Fanconi Syndrome 

Elevated SCr 

Proteinuria 

Glucosuria 

Hypophosphatemia 

ls/mm3 CD4+ Cell Count (cell ) 

Full Immune Recovery Is Associated With 

Higher Baseline CD4+ Count 

900 

800 

700 

600 

500 

400 

300 

200 

100 

0 

Moore R, et al. IAC 2006. Abstract THPE0109. 

Baseline CD4+ cell count 

< 200 cells/mm 3 

201-350 cells/mm 3 

> 350 cells/mm 3 

0 1 2 3 4 5 6 

Year of Follow-up 

GS934: Week‐48 Virologic Response 

• N = 517 antiretroviral‐naive 

patients randomized to: 

– TDF + FTC + EFV 

– ZDV/3TC + EFV 

• Superior efficacy with TDF + 

FTC 

• More discontinuations for 

h HIV-1 RNA 

< 400 Copies/mLL 

[TLOVR] (%) 

AEs with ZDV/3TC Patients With 

100 

80 

60 

P = .034 

77% 

68% 

40 

20 

0 

FTC + TDF + EFV 

ZDV/3TC + EFV 

(ITT n = 509) 

BL 8 16 24 32 40 48 

Weeks 

NNRTI 

Nonnucleoside Reverse Transcriptase Inhibitors 

Efavirenz > Rilpivirine > Nevirapine 

8/30/2012 

4

HIV‐1 RNA < 500 

c/mL, % 

Proportion With HIV-1 H RNA 

< 400 copies/mmL 

(%) 

100 

80 

60 

40 

20 

266‐006: Sustained Virologic 

Response With EFV 

100 

80 

60 

40 

IDV + ZDV + 3TC (n = 415) 

EFV + ZDV + 3TC (n = 422) 

EFV + IDV (n = 429) 

20 

P < .0001 EFV vs IDV triple-drug arm at Week 168. 

0 

B/L 12 24 36 48 60 72 84 

Weeks 

96 108 120 132 144 156 168 

Rilpivirine vs Efavirenz 96 weeks 

84% 

82% 

78% 

78% 

RPV 25 mg QD (n = 686) 

EFV 600 mg QD (n = 682) 

0 

024 8 12 16 24 32 40 48 

Wks 

60 72 84 96 

Trade‐Offs: Efavirenz‐Based Regimens 


• Long history of use; much clinical trial data 

• Current gold standard for first‐line therapy 

• As effective or more effective than other 

regimens in head‐to‐head comparisons 

• 1 pill QD coformulation of EFV/TDF/FTC 

Patients Without 

Virologic Failure (%) 

100 

80 

60 

40 

20 

0 

ACTG 5202: 96-Wk Results 

83.4 85.3 

• Low genetic barrier to resistance—single 

mutation 

• CNS adverse effects 

• Teratogenicity 

• Potential drug interactions (CYP450) 

89.0 89.8 

ABC/3TC TDF/FTC 

ATV/RTV 

EFV 

Patients (% %) 

Efavirenz Adverse Effects 

• CNS 

dizziness sleep disturbances agitation 

vivid dreams impaired concentration 

• Hyperlipidemia (modest) 

• Rash 

• Drug induced hepatitis (rarely) 

• Pregnancy category D 

• False + urine toxicology screen for THC 

• Drug interactions‐ CYP3A4 enzyme induction, effect on other 

CYP enzymes not clear 

15 

12 

6 

3 

0 

Causes of Failure at Wk 96 

14 

9 7.6 

346 

686 682 

Virologic 

Failure 

RPV (n = 686) 

EFV (n = 682) 

4.1 

686 

85 8.5 

682 

Adverse 

Events 

• More virologic 

failures with RPV vs 

EFV 

– Difference due to more 

VF between if BL VL > 

100,000; 

• D/C due to AE more 

common with EFV vs RPV 

Trade‐Offs: Rilpivirine‐Based Regimens 


• Less CNS side effects, well tolerated ‐ Cross resistance to 

• Pregnancy Category B other NNRTIs 

• More favorable lipid profile ‐ Not recommended 

• Smallest tablet VL>100 000 

• Smallest tablet VL>100,000 

‐ Expensive 

‐ Must be taken with 

food 

‐ DI with H2 blockers 

and PPI 

‐ Coformulation not 

covered on Medicaid 

8/30/2012 

5

Protease Inhibitors 

• Require “boosting” with ritonavir 

Darunavir/r = Atazanavir/r > lopinavir/r 

All other PIs 

ARTEMIS: DRV/RTV vs LPV/RTV in Treatment‐ 

Naive Patients 

• Randomized, open‐label phase III study 

• Primary endpoint: HIV‐1 RNA < 50 copies/mL at Week 48 

Antiretroviral-naive patients 

(N = 689) 

Week 48 primary endpoint [1] Week 96 [ 

DRV/RTV 800/100 mg QD 

+ TDF/FTC 

(n = 343) 

LPV/RTV 400/100 mg BID or 800/200 mg QD* 

+ TDF/FTC 

(n = 346) 

*Dosing based on regulatory approval; 77% of patients received BID dosing. 

ARTEMIS: Wk 96 Lipid Substudy 

• Statistically greater % increases in 

TC, TG in LPV/RTV arm than 

DRV/RTV arm (P < .001) 

Median Increase at Wk W 96 (mg/dL) 

60 

50 

40 

30 26 

20 

10 

0 

35 

17 15 

DRV/RTV 

LPV/RTV 

TC LDL-C HDL-C TG 

5 

8 

18 

56 

Plasma Conceentration 

Boosting PI Levels With ritonavir 

Moyle G, et al. Drugs. 1996;51:701-712. 

Time 

boosted PI 

ARTEMIS: Week 48 and 96 Response 

PI toxicity 

threshold 

PI level required 

to overcome 

“resistant” virus 

PI PI level required to 

overcome WT virus 

48 weeks non‐inferior, 96 weeks superior‐ this is the first head‐head PI trial in 

Tx naïve pts that showed superiority 

HIV-1 RNA < 50 copies/mmL 

(% [±SE]) 

100 

80 

60 

40 

20 

0 

0 

84% 

78% 

DRV/RTV (n = 343) 

LPV/RTV (n = 346) 

8 16 24 36 48 

Weeks 

60 72 84 96 

79% 

71% 

CASTLE: ATV/RTV vs LPV/RTV in Treatment‐Naive 

Patients 

• Multicenter, randomized, open‐label phase III study 

• Primary endpoint: HIV‐1 RNA < 50 copies/mL at Week 48 

Antiretroviral-naive 

(N = 883) 

ATV/RTV 300/100 mg QD + 

TDF/FTC FDC 

(n = 440) 

LPT/RTV 400/100 mg BID* + 

TDF/FTC FDC 

(n = 443) 

Week 48 

8/30/2012 

6

CASTLE: Week 48 Response to ATV/RTV vs 

LPV/RTV in Naive Patients 

ITT-CVR, NC = F 

100 ATV/RTV (n = 440) 

LPV/RTV (n = 443) 

80 

HIV-1 RNA R 

< 50 copies s/mL (%) 

60 

40 

20 

Primary endpoint 

78% 

76% 

Estimated difference: 1.7% 

(95% CI: -3.8% to 7.1%; P = NS) 

0 

0 4 12 24 

Weeks 

36 48 

• At 96 weeks, significantly more patients in the ATV/RTV arm achieved HIV‐1 RNA < 50 

copies/mL vs patients receiving LPV/RTV: 74% vs 68% ( p < .05]) 

Protease Inhibitors Adverse Effects 

• Gastrointestinal intolerance 

• Rash (fosamprenavir = daruanvir > atazanavir) 

• Hyperbilirubinemia (Atazanavir) 

• Hepatitis (Rarely) 

Hepatitis (Rarely) 

• Dyslipidemia/metabolic syndrome 

(Kaletra > other PIs) 

STARTMRK: RAL vs EFV in Treatment‐Naive 

Patients 

• Randomized, placebo‐controlled trial 

– Primary endpoint: HIV‐1 RNA < 50 copies/mL at Wk 48 

HIV-infected, treatment-naive 

patients with HIV-1 RNA 

> 5000 copies/mL and 

no resistance to EFV, 

TDF, or FTC 

(N = 563) 

Wk 48 

primary endpoint 

RAL 400 mg BID + TDF/FTC 

(n = 281) 

EFV 600 mg QHS + TDF/FTC 

(n = 282) 

Wk 96 

planned 

follow-up 

CASTLE: Mean Change in Fasting Lipids at Week 48 

Lipid Measurement Mean Change From Baseline to Week 

48, % 

ATV + RTV 

(n = 440) 

LPV/RTV 

(n = 443) 

P Value 

TC 12 24 < .0001 0001 

LDL cholesterol 12 15 NR 

HDL cholesterol 27 32 NR 

Non-HDL cholesterol 7 21 < .0001 

TG 13 51 < .0001 

• Less GI toxicity, higher rate of hyperbilirubinemia 

INSTIs 

HIV Integrase Strand Transfer Inhibitors 

• Raltegravir (Isentress, Merck) 

‐ FDA approved 2009 

‐ BENCHMRK, STARTMRK, SWITCHMRK, REALMRK 

• El Elvitegravir it i (Gil (Gilead) d) 

‐ Phase III clinical trials “QUAD Pill” 

‐ FDA approval 1st quarter 2013? 

• Dolutegravir (ViiV) 

‐ Phase III clinical trials completed 

Patie ents With HIV-1 

RNA < 50 copies/mL 

(%) 

STARTMRK: Virologic Efficacy at Wk 96 

100 

80 

60 

40 

20 

86% 

82% 

81% 

79% 

Noninferiority 

P value < .001 

0 

0 2 8 16 24 32 

Number of Contributing Patients 

40 48 60 

Study Week 

72 84 96 

RAL n = 281 281 281 279 278 280 280 281 281 280 281 

EFV n = 282 282 281 282 280 281 281 282 282 281 282 

• Significantly shorter time to virologic response with RAL vs EFV (P = .001) 

• Similar CD4+ cell count increases with RAL vs EFV 

• +240 vs +225 cells/mm3 ; 

RAL 

EFV 

8/30/2012 

7

Mean Change (mg/ /dL) 

STARTMRK: Lipid Changes From Baseline to 

Week 96 

40 

30 

20 

10 

0 

-10 

10 

38 

P < .001 for all lipid 

parameters 

3 

10 

21 

TC HDL-C LDL-C TG 

7 

Elvitegravir 

(Gilead) 

-4 

40 

RAL 

EFV 

• Requires boosting 

• Ritonavir increases systemic exposure ~ 20 

fold and half‐life 3 fold allowing for QD dosing 

• Potent HIV Integrase Inhibitor 

• Led to development of Cobicistat 

Coformulated “QUAD Pill” 

Tenofovir/emtricitabine/cobicistat/elvitegravir 

300mg / 200mg / 150mg / 150mg 

QUAD Regimen Noninferior to ATV/RTV Regimen 

at Wk 48 

HIV-1 RNA R < 50 c/mL 

at Wk 48 (%) 

100 

80 

60 

40 

20 

0 

90 87 

93 90 

Overall HIV-1 RNA 

≤ 100,000 c/mL 

85 

82 

HIV-1 RNA 

> 100,000 c/mL 

QUAD (n=353) 

ATV/RTV + Truvada 

(n = 355) 

• Similar CD4+ cell count increases in both study arms at Wk 48 

DeJesus E, et al. CROI 2012. Abstract 627. 

Raltegravir Adverse Events 

• Well tolerated – N/V/HA most common AE from 

clinical trials 

‐ creatinine kinase 

‐ myopathy 

‐ ffew cases of f rhabdomyolysis hbd l i with/without ih/ ih ARF 

• Safe with no dosage change during pregnancy 

Lennox J, et al. ICAAC 2009. Abstract H-924b. 

Virologic Success 

(%) 

100 

80 

60 

40 

20 

0 

88 

Quad vs. Atripla 

Efficacy by Baseline VL & CD4 

84 

90 

Sax P, et al. CROI 2012; Seattle. Oral #101LB 

QUAD EFV/FTC/TDF 

85 

84 82 

83 84 

Overall ≤100,000 >100,000 ≤350 >350 

HIV RNA CD4 

Quad was non-inferior to EFV/FTC/TDF at Week 48 

Elvitegravir vs Raltegravir 

• Equally efficacious 

• QD vs BID 

• Both well tolerated 

‐ Few discontinuations due to adverse effects 

• Drug Interactions > ELV 

• Cross resistance 

• Coformulation 

• COST ? 

• Will any of this matter once Dolutegravir is available? 

91 

84 

8/30/2012 

46 

8

Dolutegravir 

ViiV 

• QD integrase inhibitor without booster 

• Lipid neutral 

• Well tolerated 

• No CYP P450 drug interactions 

‐ Metabolized via glucuronidation 

• Active against RAL/ELV resistant mutations 

• Coformulation with Epzicom in the future? 

Drug Interactions 

Ritonavir > all other PIs = EFV > Raltegravir 

Atazanavir Drug Interactions 

• Must use ritonavir boosted ATZ with tenofovir ( ATZ AUC 25%) 

• Proton Pump Inhibitors 

• Tx‐naïve: PPI should not exceed dose comparable to 

omeprazole 20 mg qd (OTC dose) and must be taken 12 hours 

prior to boosted ATZ. 

• Tx‐experienced: PPI should not be used 

• H2 Antagonists 

Tx‐naïve: ATZ should be given 2 hours before or 10 hours after 

H2 blocker 

Tx‐experienced: ATZ can be given simultaneously or 10 hours 

after H2 blocker or increase ATZ dose to 400 mg/ritonavir 100 

mg if both tenofovir and H2 blocker. 

SPRING‐1: Dolutegravir vs Efavirenz in ART‐Naive 

Patients—Wk 48 Results 

HIV-1 RNA < 50 copies/mL (%) 

100 

80 

60 

40 

20 

0 

0 2 4 

8 12 16 20 24 

Wks 

Van Lunzen J, et al. IAS 2011. Abstract TUAB0102. 

91 

90 

88 

82 

DTG 10 mg QD DTG 50 mg QD 

DTG 25 mg QD EFV 600 mg QD 

Each with ABC/3TC or TDF/FTC 

Protease Inhibitor (Norvir) Drug Interactions 

• Buprenorphine / Methadone‐ OK 

• Phenytoin‐ dual DI, decreased PI and phenytoin levels 

• Trazodone‐ 3 fold increase in AUC, use with caution. 

• Voriconazole‐ Can use with low dose RTV (100 mg bid), 

voriconazole AUC deceased 40%, Cmin 25% 

• Warfarin‐ decrease R‐warfarin active metabolite AUC 33%, , monitor 

• Ca Channel Blockers‐ increase AUC for all CCB 

• Statins‐ Simvastatin and lovastatin contraindicated, increase AUC 

for atorvastatin and rosuvastatin. 

• Fluticasone‐ contraindicated 

• Erectile Dysfuction‐ start low go slow: sildenafil 25 mg, vardenafil 

2.5 mg in 72 hours 

Antiretroviral Drug Interactions 

Hepatitis C Protease Inhibitors 

Telaprevir (Incivek) Boceprevir (Victrelis) 

• $49,200 for 12 week 

treatment 

• Acceptable HAART regimens: 

– Atazanavir/ritonavir 

– Atripla 

– Raltegravir 

• Dose increase with Atripla or 

EFV to 1125 mg (3 tabs) po 

q8h 

32 

40 

48 

• $1,100/week of treatment 

• Acceptable HAART regimens: 

‐ Raltegravir 

•Do NOT adminster with NNRTIs or 

boosted PIs 

8/30/2012 

9

RAL Drug Interactions 

• Does not inhibit, induce, nor is RAL a substrate of CYP 450 

enzymes: glucuronidation (UGT1A1) 

• Rifamycins 

– 40% reduction in RAL AUC; RAL dose increased to 800 mg 

BID when administered with rifampin 

– No dose adjustment with rifabutin 

References 

• Guidelines for the use of antiretroviral agents in HIV‐ 

1‐infected adults and adolescents. Department of 

Health and Human Services. 1‐239. Available at: 

http://www.aidsinfo.nih.gov 

• Thompson, MA et al. IAS‐USA Guidelines. JAMA 

2012;308:387‐402. 

• http://www.hiv‐druginteractions.org 

Efavirenz Drug Interactions 

• Hepatic enzyme induction 

‐ Methadone 

‐ Calcium channel blockers 

‐ St Statins ti (t (atorvastatin, tti simvastatin, i t ti pravastatin) tti) 

‐ Itraconazole, voriconazole ( 400mg bid, EFV 300 mg qd) 

‐ Rifabutin (increase dose to 450 mg qd) 

‐ Warfarin (monitor INR closely) 

‐ Erectile Dysfunction drugs ( AUC) 

8/30/2012 

10

Dosing and Administration 

Challenges for Patients with 

Multiple Myeloma: 

6:30am – 7:00am 

7:00am – 7:10am 

Illinois Council of Health‐System Pharmacists 

Saturday, September 15, 2012 ~ 6:30am – 8:30am 

Drury Lane Theater, Oakbrook Terrace, IL 

Agenda 

Breakfast & Registration 

Welcome & Introductions 

Shawna Kraft, PharmD, BCOP 

7:10am – 7:30am Multiple Myeloma 101 

Newly-Diagnosed Patient/Multi-drug 

Regimen (ASCT eligible) 

Kathryn Schultz Schultz, PharmD PharmD, BCPS BCPS, BCOP 

7:30am – 7:55am Emerging Therapeutics and Administration 

Challenges 


7:55am – 8:20am Administration Challenges, Adverse Effect 

Management and Comorbidities: 

Personalized Medicine in Multiple Myeloma 


8:20am – 8:30am 

Question-and-Answer Session 

Registered Pharmacy Designation 

Registered Pharmacy Designation 

MLI is accredited by the Accreditation 

Council for Pharmacy Education (ACPE) 

as a provider of continuing pharmacy 

education. Completion of this activity 

provides 1.5 contact hour (0.15 CEU) of 

continuing education credit. 

The universal activity number for this 

activity is 0468-9999-12-004-L01-P. 

Welcome 

& 

Introductions 


Clinical Pharmacist Hematology/Oncology 

Adjunct Clinical Assistant Professor 

University of Michigan Health System 

Ann Arbor, MI 

Kathryn Schultz, PharmD, BCOP, BCPS 

Clinical Pharmacist 

Hematology/Oncology and Stem-Cell Transplant 


Chicago, IL 


• For newly diagnosed patients, identify initial dose 

adjustments that are required based on patientand 

disease-associated factors for all drugs in the 

chosen regimen to ensure maximum efficacy and 

tolerability 

• Assess the pharmacokinetics and 

pharmacodynamics of emerging agents when 

integrating these agents into treatment regimens 

• Evaluate adverse event management strategies for 

patients with MM receiving novel therapies and 

multi-drug regimens 

Purpose Statement 

CE Information 

• This program will provide health system pharmacists with reasoning 

tools they can employ when making dosing and administration 

decisions for complicated patients with MM 

Target Audience 

• This knowledge-based activity was developed for health system and 

oncology pharmacists as well as pharmacy technicians who wish to 

enhance their competence concerning regional/system variations 

in the delivery of care for patients with Multiple Myeloma 

Commercial Support Acknowledgment 

This activity is supported by an educational grant from 

Millennium: The Takeda Oncology Company 

Sponsor 

This activity is jointly sponsored by 

Medical Learning Institute, Inc. (MLI), 

and Center of Excellence Media, LLC (COE)

Instructions for Credit 

In order to receive credit for the educational activity, 

please take a few minutes to complete this 

evaluation form and hand it to the on-site 

coordinator. Your certificate of credit will be e-mailed 

to you y within 2-4 weeks. 

If you choose to complete this certificate off- site, 

return it by mail or fax to: Medical Learning Institute, 

Inc., 203 Main Street, Suite 249, Flemington, NJ 08822 / 

609.333.1694 (fax) and your certificate of credit will be 

e-mailed to you within four weeks. 

Disclosures 

Before the activity, all faculty and anyone who is in a position to have 

control over the content of this activity and their spouse/life partner will 

disclose the existence of any financial interest and/or relationship(s) 

they might have with any commercial interest producing health care 

goods/services to be discussed during their presentation(s): honoraria, 

expenses, grants, consulting roles, speakers bureau membership, stock 

ownership, or other special relationships. Presenters will inform 

participants of any off-label discussions. All identified conflicts of interest 

are thoroughly vetted by MLI for fair balance, scientific objectivity of 

studies t di mentioned ti d i in th the materials t i l or used d as th the basis b i f for content, t t and d 

appropriateness of patient care recommendations. 

The planners and managers reported the following financial relationships 

or relationships to products or devices they or their spouse/life partner 

have with commercial interests related to the content of this CE activity: 

Name of Planner or Manager Relationship Company Reported Financial 

Relationship 

Nancy Nesser MLI Nothing to Disclose 

Linda M Ritter, PhD COE Nothing to Disclose 

Multiple Myeloma 

101 

Disclaimer 

• The information provided at this CE activity is for 

continuing education purposes only and is not 

meant to substitute for the independent medical 

judgment of a healthcare provider relative to 

diagnostic and treatment options of a specific 

patient’s patient s medical condition condition. 

• Recommendations for the use of particular 

therapeutic agents are based on the best 

available scientific evidence and current clinical 

guidelines. No bias towards or promotion for any 

agent discussed in this program should be 

inferred. 

Faculty Disclosures 

• Shawna Kraft, PharmD, BCOP has nothing to 

disclose. She does not intend to discuss any non- 

FDA-approved or investigational use of any 

products/devices. 

• Kathryn Schultz, PharmD, BCPS, BCOP has nothing 

to disclose. She does not intend to discuss any non- 

FDA-approved or investigational use of any 

products/devices.


• Progressive hematologic disorder 

• Accumulation of cancerous plasma cells 

• Overproduction of abnormal immunoglobulins (“M 

proteins” or “paraproteins”) in bone marrow 

─ Mainly IgG or IgA 

─ Excessive light chain production 

─ Bence Jones proteins 

← “Monoclonal 

spike” 

Nau KC, Lewis WD. Am Fam Physician. 2008;78(7):853‐859. 

Durie BGM. Concise Review of the Disease and Treatment Options 2008/2009 Edition. International Myeloma Foundation; 2009. 


Epidemiology 

• ~21,700 new cases estimated for 2012 

• ~10,710 deaths estimated for 2012 

• Lifetime risk is 1 in 155 (based on rates 

from 2006-2008) 

• 5 year survival increased from 25% in 

1975 to 41% in 2007 

American Cancer Society. Cancer Facts & Figures 2012. Atlanta: American Cancer Society; 2012. 

Howlander N, et al (eds). SEER Cancer Statistics Review, 1975‐2008, National Cancer Institute. Bethesda, MD, 

http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to the SEER web site, 2011. 

• Ultimately unknown 

Etiology 

• Possible explanations 

─ Hereditary linkage 

─ Genetic abnormalities 

─ Exposure to radiation 

─ Viral infection 

─ Progression of MGUS 

Landgren O, Korde N. Oncology (Williston Park). 2011;25(7):589‐590. 

Long‐lived 

plasma cell 

Myeloma Progression 

MGUS 

Germinal‐ 

center B‐cell IgH translocation Secondary Changes 

Genetic Changes 

Smoldering Smolderingg Intramedullary 

Intramedullaryy 

Extramedullary 

myeloma myeloma myeloma 

Changes in BM Microenvironment Interaction 

Bone Destruction 

MGUS = Monoclonal gammopathy of undetermined significance 

Shain et al. Multiple myeloma. In: Runge and Patterson, eds. Molecular Medicine. 2 nd ed. Humana Press; 2006. 


Survival 

• The 5-year relative survival rate for MM is currently estimated at 

~41% 

• Survival is higher in younger people and lower in the elderly 

• 5-year survival rates are based on patients diagnosed and 

iinitially iti ll ttreated t d more th than 5 years ago (2001 (2001-2007) 2007) 

• The recent improvements in treatment may result in a more 

favorable outlook for recently diagnosed patients 

• Improvements in prognosis have occurred because of the 

introduction of newer therapies such as pulse corticosteroids, 

immunomodulators (thalidomide, lenalidomide), and a 

proteasome inhibitor (bortezomib) 

Brenner H, et al. Haematologica. 2009; 94(2): 270–275. Howlander et al (eds). SEER Cancer Statistics Review, 1975‐2008, National 

Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER data submission, posted to 

the SEER web site, 2011. 

Diagnostic Criteria for 

Symptomatic MM 

1. Monoclonal plasma cells in the bone marrow >10% 

and/or presence of a biopsy-proven plasmacytoma 

2. Monoclonal protein present in the serum and/or urine 

3. Myeloma-related organ dysfunction (1 or more) 

Organ Dysfunction Criteria 

Calcium elevation Serum calcium ≥11.5 mg/dL 

Renal Insufficiency Serum creatinine >2 mg/dL 

Anemia Hemoglobin 2 g/dL below LLN 

Bone Lytic lesions, severe osteopenia, or pathologic 

fractures 

LLN=Lower limit of normal 

International Myeloma Working Group. Br J Haematol. 2003;121:749‐757. 

Kyle RA, et al. Leukemia. 2009;23(1):3‐9.

Staging 

Stage Criteria (Durie‐Salmon) Criteria (International Staging System) 

I All of the following: 

Hemoglobin >10 g/dL 

Serum Ca

Standard Risk 

• Hyperdiploidy 

• t(11;14) 

• t(6;14) 

Kapoor et al. Int J Hematol. 2011;94:310‐320. 

Rajkumar. Am J Hematol. 2012;87:79‐88. 

Risk Stratification 

Intermediate 

Risk 

• t(4;14) 

•Deletion 13 or 

hhypodiploidy di l id bby 

conventional 

karyotyping 

High Risk 

• 17p deletion 

• t(14;16) 

• t(14;20) 

•High‐risk gene 

expression 

profiling (GEP) 

signature 

•Plasma cell 

leukemia 

Newly Diagnosed Myeloma Eligible for 

Transplantation 

High High‐Risk Risk Intermediate 

Intermediate‐Risk Risk Standard Standard‐Risk Risk 

VRD x 4 cycles VCD x 4 cycles 

Rd x 4 cycles 

ASCT 

Bortezomib‐based 

maintenance 

Rajkumar SV. Am J Hematol. 2012;87:79‐88. 

ASCT; 2 nd ASCT if 

not in CR or VGPR 

Bortezomib 

maintenance for 

2 years 

Early 

ASCT 

Delayed 

ASCT 

Lenalidomide 

maintenance if not 

in CR or VGPR 

following ASCT 

Newly Diagnosed Myeloma Not Eligible 

for Transplantation 

High High‐Risk Risk Intermediate 

Intermediate‐Risk Risk Standard Standard‐Risk Risk 

VRD x one year VCD x one year 

Rd* 

Bortezomib‐based 

maintenance 

Rajkumar SV. Am J Hematol. 2012;87:78‐88. 

Bortezomib 

maintenance for 

2 years if possible 

*Dexamethasone usually discontinued after 12 months; continued long‐term bortezomib or lenalidomide is an 

option for patients who are tolerating treatment well. 

Induction Therapy for 

Transplant Candidates 

Regimen NCCN Category 

Bortezomib/dexamethasone 

1 

Bortezomib/doxorubicin/dexamethasone 

1 

Bortezomib/thalidomide/dexamethasone 

1 

Lenalidomide*/dexamethasone 

1 

BBortezomib/cyclophosphamide/dexamethasone BBortezomib/cyclophosphamide/dexamethasone t ib/ l h h id /d th 

2A 

Bortezomib/lenalidomide*/dexamethasone 

2A 

Thalidomide/dexamethasone 2B 

Dexamethasone 2B 

Liposomal doxorubicin/vincristine/dexamethasone 2B 

*Consider harvesting peripheral blood stem cells prior to prolonged exposure to lenalidomide. 

Category 1 –The recommendation is based on high‐level evidence and there is uniform NCCN consensus 

Category 2A –The recommendation is based on lower‐level evidence and there is uniform NCCN consensus 

Category 2B –The recommendation is based on lower‐level evidence and there is nonuniform NCCN consensus 

The NCCN Clinical Practice Guidelines in Oncology Multiple Myeloma (Version 1.2012). © 2011 National Comprehensive Cancer 

Network, Inc. Available at: NCCN.org. Accessed [March 13, 2012]. To view the most recent and complete version of the NCCN 

Guidelines, go online to NCCN.org. 

Induction Therapy for 

Nontransplant Candidates 


Melphalan/prednisone/bortezomib 

1 

Melphalan/prednisone/thalidomide Melphalan/prednisone/thalidomide 

1 

Melphalan/prednisone/lenalidomide 

1 

Lenalidomide/low‐dose dexamethasone 

1 

Bortezomib/dexamethasone Bortezomib/dexamethasone 

2A 

Melphalan/prednisone 2A 

Dexamethasone 2B 

Vincristine/doxorubicin/dexamethasone 2B 

Thalidomide/dexamethasone 2B 

Liposomal doxorubicin/vincristine/dexamethasone 2B 






Guidelines, go online to NCCN.org. 

Maintenance Therapy 


Thalidomide 

1 

Bortezomib 

2A 

Lenalidomide* 

2A 

Interferon f 

2B 

Steroids 2B 

Thalidomide/prednisone 2B 

*There appears to be an increased risk for secondary cancers, especially with lenalidomide 

maintenance following transplant. The benefits and risk of maintenance therapy vs secondary cancers 

should be discussed with patients. 






Guidelines, go online to NCCN.org.

Salvage Therapy 

Partial List 


Bortezomib 

1 

Bortezomib/liposomal doxorubicin 

1 

Lenalidomide/dexamethasone* Lenalidomide/dexamethasone 

1 

Repeat primary induction (relapse > 6 mos) 2A 

Bendamustine 2A 

Bortezomib/dexamethasone / 

2A 

Bortezomib/lenalidomide/dexamethasone 2A 

Cyclophosphamide/bortezomib/dexamethasone 2A 

Cyclophosphamide/lenalidomide/dexamethasone 2A 

Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) 2A 

Dexamethasone, thalidomide, cisplatin, doxorubicin, 

cyclophosphamide, etoposide (DT‐PACE) ±bortezomib(VTD‐PACE) 

2A 

High‐dose cyclophosphamide 2A 

Thalidomide/dexamethasone 



2A 

The NCCN Clinical Practice Guidelines in Oncology Multiple Myeloma (Version 1.2012). © 2011 National Comprehensive Cancer Network, Inc. Available at: 

NCCN.org. Accessed [March 13, 2012]. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. 

Objectivve 

Response (%) 

Previously Untreated Multiple Myeloma 

Response 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

40‐46 

35‐48 35 48 

52 

63‐76 

88‐90 

68‐91 

1‐3 4,5 6 1,2,6 7,8 9,10 

Dex MP VAD Thal/Dex Bor/Dex Len/Dex 

1.Rajkumar et al. J Clin Oncol. 2006;24(3):431‐436. 2. Rajkumar et al. J Clin Oncol. 2008;26(13):2171‐2177. 3. Facon et al. Blood. 

2006;107(4):1292‐1298. 4. San Miguel et al. N Engl J Med. 2008;359(9):906‐917. 5. Palumbo et al. Lancet. 2006;367(9513):825‐ 

831. 6. Cavo et al. Blood. 2005;106(1):35‐39. 7. Jagannath et al. Br J Haematol. 2005;129(6):776‐783. 8. Jagannath et al. Br J 

Haematol. 2009;146(6)619‐626. 9. Rajkumar et al. Lancet Oncol. 2009 Oct 21 [Epub ahead of print]. 10. Rajkumar et al. Blood. 

2005;106(13):4050‐4053. 

Bortezomib/Dexamethasone 

(Bor/Dex) vs VAD as Induction 

Treatment Prior to Autologous Stem 

Cell Transplantion (ASCT) in Newly 

Diagnosed Multiple Myeloma (MM): 

Results of the 

IFM 2005/01 Trial 

Jean‐Luc Harousseau, Michel Attal, Herve´ Avet‐Loiseau, Gerald Marit, Denis 

Caillot, Mohamad Mohty, Pascal Lenain, Cyrille Hulin, Thierry Facon, Philippe 

Casassus, Mauricette Michallet, Herve´ Maisonneuve, Lotfi Benboubker, Frederic 

Maloisel, Marie‐Odile Petillon, Iain Webb, Claire Mathiot, and Philippe Moreau 

Harousseau,et al. J Clin Oncol. 2010;28(30):4621‐4629. 

Grade 3/4 

AEs 

Emerging Therapeutics 

and Administration 

Challenges 

Lenalidomide/ 

Dexamethasone Toxicity 

Len/Dex 

n = 177 

MM 009 MM 010 

Dex 

n = 175 

Len/Dex 

n = 176 

Dex 

n = 175 

Neutropenia 41.2% 4.6% 29.5% 2.3% 

Thromboc Thrombocytopenia topenia 14 14.7% 7% 69% 6.9% 11 11.4% 4% 57% 5.7% 

Anemia 13.0% 5.1% 8.6% 6.9% 

Febrile neutropenia 3.4% 0% 3.4% 0% 

Venous thromboembolism 14.7% 3.4% 11.4% 4.6% 

• Most frequently reported nonhematologic AEs 

– Fatigue, insomnia, diarrhea, constipation, muscle cramps, 

and infection 

Weber et al. N Engl J Med. 2007;357:2133‐2142. 

Dimopoulos et al. N Engl J Med. 2007;357:2123‐2132. 

Response 

Post‐Induction 

IFM 2005/01 Trial 

Response 

Bor/Dex* 

N = 214 

VAD* 

N = 210 

CR 5.8% 1.4% .012 

>VGPR 37.7% 15.1% < .001 

>PR 78.5% 62.8% < .001 

Response to First 

ASCT 

Bor/Dex* 

n = 212 

VAD* 

n = 213 

CR 16.1% 8.7% .016 

>VGPR 54.3% 37.2% < .001 

>PR 

*+ DCEP consolidation. 

80.3% 77.1% NS 

VAD= Vincristine, Adriamycin, Dexamethasone; DCEP= Dexamethasone, cyclophosphamide, etoposide and cisplatin 

Harousseau, et al. J Clin Oncol. 2010;28(30):4621‐4629. 

P 

P

Treatment Considerations 

• Lenalidomide/Dex vs. Thalidomide/Dex 

─ OS: Not reached vs. 57.2 mos. (P=.018) 

─ Neutropenia (3/4): 14.6% vs 0.6% (P

Bortezomib-Thalidomide-Dexamethasone 

Compared with Thalidomide- 

Dexamethasone as Induction and 

Consolidation Therapy Before and After 

Double Autologous Transplantation In Newly 

Diagnosed Multiple Myeloma: Results From a 

Randomized Phase 3 Study 

Michele Cavo, Giulia Perrone, Silvia Buttignol, Elisabetta Calabrese, Monica Galli, 

Sara Bringhen, Tonino Spadano, Luca Baldini, Tommaso Caravita, Chiara Nozzoli, 

Annamaria Brioli, Luciano Masini, Anna Furlan, Lucia Pantani, Daniele Derudas, 

Stelvio Ballanti, Francesco Pisani, Valerio De Stefano, Gioacchino Catania, Luca 

Castagna, Felicetto Ferrara, Vincenzo Callea, Pellegrino Musto, Elena Zamagni, 

and Michele Baccarani 

Seragnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy; 

Department of Hematology/Oncology, University of Bologna, Bologna, Italy; 3GIMEMA Italian 

Myeloma Network, Italy 

Cavo M, et al. Blood (ASH Annual Meeting Abstracts). 2010;116:42. 

Increased CR-nCR Rates with 

VTD Compared to TD 

Percent 

80 

70 

60 

50 

40 

30 

20 

10 

0 

P

Administration of bortezomib before and 

after autologous stem-cell transplantation 

improves outcome in multiple myeloma 

patients with deletion 17p 

Kai Neben, Henk M Lokhorst, Anna Jauch, Uta Bertsch, Thomas Hielscher, 

Bronno van der Holt, Hans Salwender, Igor W Blau, Katja Weisel, Michael 

Pfreundschuh, Christof Scheid, Ulrich Duhrsen, Walter Lindemann, Ingo GH 

Schmidt-Wolf, Norma Peter, Christian Teschendorf, Hans Martin, Mathias 

Haenel, Hans G Derigs, Marc S Raab, Anthony D Ho, Helgi van de Velde, 

Dirk Hose, Pieter Sonneveid and Hartmut Goldschmidt 

Neben K, et al. Blood. 2012;119(4):940‐948. 

Overall results 

Results 

PFS 3 yr OS Median OS 

VAD (N = 182) 

PAD (N = 172) 

31.2 months 

35.7 months 

73% 

84% 

Not reached 

17 17q deletion dlti results lt 

17q deletion present 17.6 mos 

PFS 3 yr OS 

VAD 12.0 mos* VAD 17% 

36% 

† 

PAD 26.2 mos* PAD 69% † 

Lacking abnormality 35.7 mos 83% 

*P = .024 

† P = .028 


Question 1 - Revisited 

• What initial therapy would you initiate for RS? 

A. Melphalan/prednisone 

B. Steroids alone 

C. Thalidomide/dexamethasone 

D. Lenalidomide/high-dose 

dexamethasone 

E. Other 

INDUCTION (three 21‐d cycles) 

VAD 

• Vincristine 0.4mg IV Days 1‐4 

• Doxorubicin 9mg/m 2 IV Days 1‐4 

• Dex 40mg Days 1‐4, 9‐12, 17‐20 

PBSC COLLECTION 

• CTX, Doxorubicin, Dex (CAD) + 

G‐CSF 

TRANSPLANTATION 

• MEL 200 

Thalidomide Maintenance 

• 50mg PO Daily 

• X 2 years 

PBSC=peripheral blood stem cells 


Study Design 

RANDOMIZATION 

INDUCTION (three 21‐day cycles) 

PAD 

• Bortezomib 1.3mg/m 2 IV Days 1, 4, 8, 11 

• Doxorubicin 9mg/m 2 IV Days 1‐4 

• Dex 40mg Days 1‐4, 9‐12, 17‐20 

PBSC COLLECTION 

• CTX, Doxorubicin, Dex (CAD) + 

G‐CSF 

TRANSPLANTATION 

• MEL 200 

Patient Case 1 

Bortezomib Maintenance 

• 1.3mg/m 1.3mg/m2 IV every 2 weeks 

• X 2 years 

• RS is a 68 y.o. male presented to ED after falling while 

taking down holiday lights. In the ED, x-rays confirmed 

he had broken his right hip. He was A&O x3 with no 

other signs of trauma or bleeding. Other past medical 

history includes HTN for which he is on lisinopril and 

Type 2 DM controlled with diet. Labs were as follows: 

– Hemoglobin: 88.9 9 gm/dL 

– Serum creatinine: 1.7 mg/dL 

– Calcium: 11.9 mg/dL 

– Albumin: 1.8 g/dL 

– β2microglobulin: 3.3 mcg/mL 

– Urine analysis= urine protein= M protein spike of IgA 

– Bone marrow = 19% plasma cells 

– Skeletal survey= multiple lytic lesions 


Challenges, Adverse 

Effect Management 

and Comorbidities: 

Personalized Medicine 

in Multiple Myeloma

Case 2 

ST is a 76 y/o African American female who recently presented to 

her PCP for increasing pain in her back. PMH: Type 2 DM, HTN, CAD 

s/p stents, depression. ST was diagnosed with Stage IIIa IgG lambda 

multiple myeloma based on the following labs and exams: 

• WBC: 12 X 109 /L 

• ß₂-microglobulin: 7 mcg/mL 

• Serum creatinine: 1.7 mg/dL • IgM: 9 (4-350 mg/dL) 

• Hemoglobin: 8 gm/dL 

• Calcium: 12 mg/dL 

• Platelets: 112 X 109 /L 

• Albumin: 4 g/dL 

• IgA: 5 (50-370 mg/dL) 

• IgG: 6080 (620-1520 mg/dL) 

• � free light chains: 306 (0.57-2.63 mg/dL) 

• Plasma viscosity: 2.47 X 10−3 (1.35-1.85) 

• Skeletal survey shows multiple lytic lesions T8-T11 

Palumbo A, et al. Blood. 2011;118(17):4519‐4529. 

Case 2: Patient ST 

• She also has prexisting diabetes with 

peripheral neuropathy on gabapentin 

300mg TID. 

• What is your recommendation? 

Assessment for Vulnerability in 

Newly-Diagnosed MM Patients 

Presence of chronic 

diseases or conditions 

Comorbidity 

Actions 

• Consider drug interactions 

• Incompatibility of treatment 

• Minimize risk of frailty 

• Minimize risk of disability 

Palumbo A, et al. Blood. 2011;118(17):4519‐4529. 

Limits in the major 

life activities due to 

physical or mental 

impairment 

Disability 

Case 2 

Weight loss, fatigue, 

low activity, slow 

motor balance and 

gait 

Actions 

Frailty 

• Need for supportive service 

• Minimize risk of mortality 

• Decrease risk of hospitalization) 

• It has been decided to treat ST with 

lenalidomide + bortezomib + dexamethasone 

(RVD) 

• Lenalidomide 25 mg days 1-21 + low-dose vs. 

high dose dexamethasone Q28days 

– Low dose: 40 mg days 1, 8, 15, 22 

– High dose: 40 mg days 1-4, 9-12, 17-20 

– N = 445 

– 1- year OS = 87% (high dose) vs. 96% (low dose) , P 

= .0002 

– DVT = 26% vs. 12%, P = .0003 

– Infection or pneumonia = 16% vs. 9%, P = .04 

– Fatigue = 15% vs. 9%, P = .08 

Rajkumar SV, et al. Lancet Oncol. 2010;11(1):29‐37. 

Peripheral Neuropathy (PN) 

• Higher risk of PN 

– In patients presenting with subclinical PN 

– After prolonged therapy 

– In elderly patients 

• Clinical manifestations include sensory symptoms, 

motor symptoms, and autonomic dysfunction 

Severity Action 

Grade 1 Continue as scheduled 

Grade 1 w/ pain or grade 2 Reduce dose per course to 1.0 mg/m2 Grade 2 w/ pain or grade 3 Withhold bortezomib treatment until PN resolves, 

reinitiate at a dose of 0.7 mg/m2 once weekly 

Grade 4 Discontinue therapy 

Palumbo A, et al. Blood. 2008;111:3968‐3977. 

Argyriou AA, et al. Blood. 2008;112:1593‐1599. 

Bortezomib Dose Modification with PN

Bortezomib SQ vs. IV 

Pharmacokinetics C max (ng/mL) T max (min) AUC last (ng.hr/mL) 

SQ 20.4 30 155 

IV 223 2 151 

Pharmacodynamics E max (%) E max (min) AUE 72hr (%.hr) 

SQ 63.7 120 1714 

IV 69.3 5 1383 

Moreau P, et al. Blood (ASH Annual Meeting Abstracts). 2011;118: Abstract 1863. 

Case 2 

ST is a 76 y/o African American female who recently 

presented to her PCP for increasing pain in her back. PMH: 

Type 2 DM, HTN, CAD s/p stents, depression. ST was 

diagnosed with Stage IIIa IgG lambda multiple myeloma 

based on the following labs and exams: 

• WBC: 12 

• Scr: 11.7 7 

• ß₂-microglobulin: 7 mcg/ml 

• Hgb: 8 

• Ca: 12 

• IgG: 6080 (620-1520 mg/dL) 

• Plts: 112 

• Albumin: 4 

• IgM: 9 (4-350 mg/dL) 

� free light chains: 306 (0.57-2.63 mg/dL) 

� IgA: 5 (50-370 mg/dL) 

• Plasma viscosity: 2.47 (1.35-1.85) 

• Skeletal survey shows multiple lytic lesions T8-T11 

Treatment of Bone Disease in MM 

• Denosumab 

─ 120 mg SQ vs. zoledronic acid, N = 1176 (only 10% MM) 

─ CrCl >30 mL/min 

─ Noninferior 

• Ibandronate 6 mg, N=40 

─ CrCl 30-59 mL/min, N=10 

─ CrCl 60 mL/min, p

Thalidomide and Lenalidomide 

• Addition to therapy regimen improves 

response rates 

– Thalidomide alone: 25-35% 

– Thalidomide plus dexamethasone: 50% 

– Thalidomide Thalidomide, dexamethasone, dexamethasone alkylating agent: 

70% 

• Mechanism of action 

– Inhibits angiogenesis and induces apoptosis 

– Inhibits TNF-α and type 1 helper T-lymphocytes 

– Induces IFN-β and type 2 helper T-lymphocytes 

ASCO Guidelines. Lyman GH, et al. J Clin Oncol. 2007;25(34):5490‐5505. 

Palumbo A, et al. Leukemia. 2007; 1‐10. 

VTE and Thalidomide 

• Serum thrombomodulin levels 

─ Decreased during 1 st month of thalidomide therapy 

─ Gradual recovery over following two months 

• Protease activated receptor-1 (PAR-1) 

─ Endothelial exposure altered by thalidomide after 

doxorubicin exposure 

─ Can increase thrombin binding to the vascular 

endothelium 

• Activated protein C (APC) 

─ Patients with APC resistance in absence of factor V 

Leiden had higher incidence of DVT when treated with 

thalidomide 

Corso A, et al. Ann Hematol. 2004;83(9):588‐591. 

Kaushal V, et al. J Thromb Haemost. 2004;2(2):3273‐84. 

Zangari M, et al. Blood Coagul Fibrinolysis. 2002;13(3):187‐192. 

ASCO Recommendations 

• Routine anticoagulation for VTE prophylaxis is 

not recommended for ambulatory patients 

receiving chemotherapy 

• Patients receiving thalidomide or 

lenalidomide with dexamethasone or 

chemotherapy warrant prophylaxis 

ASCO Guidelines. Lyman GH, et al. J Clin Oncol. 2007;25(34):5490‐5505. 

Teo SK. Properties of Thalidomide and its Analogues: Implications for Anticancer Therapy. AAPS Journal. 2005; 07(01): E14‐E19. 

DOI: 10.1208/aapsj070103 

Therapy-specific Incidence of VTE 

Therapy Incidence Comments 

Thalidomide alone 1‐3% 

Thalidomide + dexamethasone 17‐26% Thal/dex vs dex: 17% vs 3% 

Thalidomide +chemotherapy py 

12‐28% 

Oral melphalan + prednisone 1.5‐2% 

Melphalan + pred + thalidomide 12‐18.5% 

Dunkley S, Gaudry L. J Thromb Haemost. 2007;5:1323‐1325. ASCO Guidelines. Lyman GH, et al. J Clin Oncol. 2007;25(34):5490‐5505. 

Palumbo A, et al. J Thromb Haemost. 2006;4:1842‐1845. Rajkumar SV, et al. J Clin Oncol. 2006;24(3):431‐436. 

Palumbo A, et al. Lancet. 2006;367:825‐831. 

Singhal S, et al. N Engl J Med. 1999;341:1565‐1571. 

Kyle RA, Rajkumar SV. N Engl J Med. 2004;351(18):1860‐1873. Zangari M, et al. Blood. 2001;98:1614‐1615. 

LMWH Literature 

Study Therapy Prophylaxis Methods Results 

GIMEMA MP vs MPT Enoxaparin 

40mg 

UARK 9826 Chemo +/‐ 

thalidomide 

Palumbo A, et al. Lancet. 2006;367:825‐831. 

Zangari M, et al. Br J Haematol. 2004;126:715‐721. 

Alikhan R, et al. Blood Coagul Fibrinolysis. 2003;14:341‐346. 

Chemotherapy 

randomized 

Prophylaxis due 

to protocol 

amendment 

Enoxaparin 3 cohorts; 

amended 

protocol from 

low‐dose fixed 

warfarin; open‐ 

label 

17% vs 9% did not 

complete 6 cycles 

MPT therapy; 

before/after 

20% vs 3.1% as a 

subgroup 

DVT: 11/35 vs 

30/87 vs 19/134

Chemotherapy 

N=134 

DVT 

N=19 

19 DVT 

Continue Treatment 

+ Anticoagulant 

DVT Recurrence 

N=1 (5%) 

Cohort I 

(No Anticoagulation) 

N=221 

Newly diagnosed Multiple Myeloma Patients enrolled 

On UARK 9826 

Chemotherapy + Thal 

N=87 

DVT 

N=30 

Zangari M, et al. Br J Haematol. 2004;126:715‐721. 

Cohort II 

(Warfarin prophylaxis) 

N=35 

DVT=41 

Chemotherapy + Thal 

+ Warfarin 

N=35 

DVT 

N=11 

36 DVT 

Continue Treatment 

Thalidomide Resumed 

+ Anticoagulant 

DVT Recurrence 

N=4 (11%) 

Chemotherapy + 

Thal + LMWH 

N=68 

DVT DVT 

N=10 

Cohort III 

N=130 

Prophylactic Low-dose Aspirin 

Study Methods Therapy 

I Retrospective Amendment Thal/dex + clarithromycin; ASA added to 

regimen 

II Prospective Randomized Dexamethasone, ± thalidomide & ASA, ± 

clarithromycin 

III Prospective Descriptive Lenalidomide & ASA 

Summary of TEs in studies I to III 

Thromboemolic events Grade 2 

(percent) 

Niesvizky R, et al. Leuk Lymphoma. 2007;48(12):2330‐2337. 

Grade ¾ 

(percent) 

Grade 5 

(percent) 

Comments 

Chemotherapy 

N=62 

Study I: BLT‐D 

Study II: Randomized BLT‐D 

8 9 ‐ No TEs after ASA was 

added to study regimen 

Group 1 ‐ 6.6 ‐ Thalidomide, 

dexamethasone, 

clarithromycin (if needed) 

and ASA 

Group 2 ‐ 21.4 ‐ Dexamthasone and 

clarithromycin (if needed) 

Study III: BiRD ‐ 10.8 1.4 

Prophylactic Aspirin 

Study Therapy Prophylaxis Methods 

Knight 1 Lenalidomide + 

dexamethasone 

(2 studies) 

Zonder 2,3 Lenalidomide + 

dexamethasone 

1. Knight R, et al. N Engl J Med. 2006;354(19):2079‐2080. 

2. Zonder JA, et al. Blood. 2006;108(1):403. 

3. Zonder JA, et al. Blood. 2010;116(26):5838‐41. 

Occurrence of 

thrombosis 

Low‐dose aspirin Preliminary report 20/87 w/ erythropoeitin 

4/83 w/o erythropoeitin 

0/23 w/ ASA 

52/668 w/o ASA 

Full‐dose aspirin Preliminary report 9/12 w/o ASA 

After protocol amendment 6%w/ ASA1 19 % w/ ASA2 DVT 

N=9 


• 105 patients were treated with vincristine, 

doxorubicin, dexamethasone, and 

thalidomide (VAD-t) 

• High rate of venous thrombosis noted after 

35 patients in the trial 

• Low-dose aspirin initiated in 26 of the original 

35 patients 

• Thrombosis 

– 19% who received aspirin from start of enrollment 

– 15% who received aspirin after the study started 

– 58% of those who never received aspirin 

Baz R, et al. Mayo Clin Proc. 2005;80:1568. 


• Not designed to assess thromboembolic risk 

• No a priori definition of TE risk factors 

• 3 study designs 

Thalidomide/ 

dexamethasone: 

Low‐dose aspirin 

Table IV. Rate of thrombosis in patients receiving low‐dose aspirin with 

thalidomide/dexamethasone 

Total number of 

patients 

Niesvizky R, et al. Leuk Lymphoma. 2007;48(12):2330‐2337. 

Number of patients 

(%): Thrombosis 

15 1 (6.6) 14 (93) 

Dexamethasone: 

No Aspirin 

14 3 (21.4) 11 (79) 

OR 3.82 (exact 95% CI, 0.25, 214.45); Fisher’s exact p value (2‐sided)=0.33. 

Warfarin 

Number of patients 

(%): No Thrombosis 

• Low-dose warfarin 

– 1 mg daily 

– Has been studied as prophylaxis for central 

venous catheter thrombosis 

• Full anticoagulation 

– Goal INR 2-3 

Coumadin (warfarin sodium) package insert. Princeton, NJ: Bristol‐Myers Squibb; 2011.

Fixed Low-Dose Warfarin 

Study Therapy Prophylaxis Methods Results 

Miller 1 MM: VAD‐t or 

VDT 

CLL: FT 

1mg if ≤ 70 kg 

2mg if > 70 kg 

No concurrent ASA; 

baseline 

hypercoagulable work‐ 

up; duration of 

treatment coincided 

with therapy (avg 4 

months) 

No significant 

difference; 

compared to 

historical controls 

UARK 98262 UARK 9826 Ch / 1 f i C h 2 (h hl DVT 11/35 

2 Chemo +/‐ 1mg warfarin Cohort 2 (chemo + thal DVT: 11/35 

thalidomide 

and warfarin) 

(c+t+w) vs 30/87 

(c+t) vs 19/134 (c) 

Trial stopped 

Weber3 Thalidomide 1mg warfarin Protocol amendment 16/40 patients 

vs thal/dex 

receiving thal/dex 

continued trial, 

but switched to 

therapeutic dose 

of warfarin or 

LMWH 

1. Miller KC, et al. Leuk Lymphoma. 2006;47(11):2339‐2343. 

2. Zangari M, et al. Br J Haematol. 2004;126(5):715‐721. 

3. Weber D, et al. J Clin Oncol. 2003;21(1):16‐19. 

VTE Prophylaxis 

• Risk factors: 

– Individual 

• History of VTE, age, obesity, cardiac disease, 

immobilization, presence of central catheter, 

surgical i l procedures d 

– Disease-related 

• Multiple myeloma diagnosis, hyperviscosity 

– Therapy-related 

• Immunomodulatory therapy (thalidomide, 

lenalidomide) in combination with high-dose 

steroids 

Gay F, Palumbo A. Med Oncol. 2010;27(suppl 1):S43‐S52. 

Summary 

• Evaluate patient specific risk factors 

– Concern for thrombocytopenia—especially with 

lenalidomide 

– Renal function 

• Thalidomide-associated therapy py 

– Full dose warfarin for high risk patients 

– LMWH for low to moderate risk patients 

• Lenalidomide-associated therapy 

– Aspirin 

• UK Thrombosis Prevention Trial 

Risk Assessment Model 

Individual risk factors Recommended therapy 

Obesity (≥ 30 kg/m2 ) If no risk factor or any one risk factor 

Previous venous Thromboembolism 

Central venous catheter or pacemaker 

is present: 

Aspirin 81‐325 mg once daily 

Associated disease: 

If two or more risk factors are present: 

•Cardiac disease •Diabetes 

LMWH (equivalent to enoxaparin 40mg once 

•Chronic renal disease •Immobilization daily) 

•Acute infection 

OR 

Surgery 

•General surgery •Trauma 

•Any anesthesia 

Medications: Erythropoietin 

Blood clotting disorders 

Myeloma‐related risk factors 

•Diagnosis •Hyperviscosity 

Full‐dose Full dose warfarin (target INR 2‐3) 2 3) 

Myeloma therapy 

LMWH (equivalent to enoxaparin 40mg once 

•High‐dose dexamethasone (≥ 480 mg/month) daily) 

•Doxorubicin 

•Multiagent chemotherapy 

Full‐dose warfarin (target INR 2‐3) 

Palumbo A, et al. Leukemia. 2008;22(2):414‐423. 

VTE Prophylaxis Options 

• If none or 1 individual or MM-related risk 

factor present: 

– Aspirin (81 mg to 325 mg daily) 

• If 2 or more individual or myeloma-related risk 

factors present: 

– Low molecular weight heparin (LMWH) 

– Full dose warfarin (target INR 2-3) 

• Therapy-related risk factors should be 

considered high-risk: 

– LMWH or full dose warfarin 

Gay F, Palumbo A. Med Oncol. 2010;27(suppl 1):S43‐S52. 

VTE Prophylaxis in MM: Guidelines 

• NCCN guidelines 

─ Aspirin 81-325 mg (low risk outpatients) 

─ Warfarin, INR 2-3 

─ LMWH 

─ Fondaparinux 

─ UFH 

• CHEST guidelines 

─ Prophylactic LMWH or LDUH over no prophylaxis 

─ Aspirin is not addressed for cancer patients 

─ VKAs 

The NCCN Clinical Practice Guidelines in Oncology Venous Thromboembolic Disease (Version 2.2011). © 2011 National 

Comprehensive Cancer Network, Inc. Available at: NCCN.org. Accessed [April 3, 2012]. To view the most recent and complete version 

of the NCCN Guidelines, go online to NCCN.org. 

Kahn SR, et al. Chest. 2012; 141(2 Suppl):e195S‐226S.

VTE Prophylaxis in MM: 

New Agents 

• Rivaroxaban 

─ FDA approved: 

• Dabigatran 

• To reduce the risk of stroke and systemic 

embolism in patients with nonvalvular Afib 

• Prophylaxis of deep vein thrombosis (DVT) 

in patients undergoing knee or hip 

replacement 

Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2011. 

Pradaxa (dabigatran etexilate mesylate) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc. 2012. 


• 73 year old male presents with refractory 

multiple myeloma 

• He is not a candidate for transplant and 

was previously treated with MP (melphalan 

plus prednisone). 

• Hi His medical di l hi history t i is significant i ifi t f for a DVT of f 

idiopathic cause when he was 55 

• His physician wants to treat him with 

thal/dex (thalidomide) since he previously 

responded to MP. 

– Would you proceed with therapy? 

– Would you recommend thromboprophylaxis? 

MM Summary 

• Treatment decisions 

─ Transplant candidate? 

─ Renal function 

─ Comorbidities 

─ Multidrug Multidrug regimens are preferred 

• Supportive care 

─ VTE prophylaxis recommended with 

thalidomide/lenalidomide regimens 

─ Bisphosphonates are preferred for bone disease 

─ Patient specific factors are very important 

─ Zoster prophylaxis for bortezomib regimens 


• 67 year old female was induced with VAD-t 

(vincristine, doxorubicin, dexamethasone, 

thalidomide) 

• She has received 2 cycles of chemotherapy 

and now presents to the hospital with unilateral 

pain and swelling in her left lower leg. 

• The VAD-t therapy has been effective, so her 

physician wants her to receive 2 more cycles of 

induction therapy before her stem-cells are 

harvested 

– Would you proceed with therapy? 

– Would you recommend thromboprophylaxis? 

Bortezomib and Herpes Zoster 

Reactivation 

• Incidence of herpes zoster in randomized Phase 3 

frontline MM trials 

Trial Bortezomib Arm Bortezomib Arm Control Arm 

No Prophylaxis with Prophylaxis 

VISTA 13% 3% 4% 

IFM 2005‐01* NA 9% 2% 

HOVON‐65/GMMG‐HD4 15% 9% 2% 

*No antiviral prophylaxis for herpes zoster was specified in the protocol. 

• Retrospective analysis of 125 patients on bortezomib 

and antiviral prophylaxis found no VZV reactivation 

– 100% compliance 

– Well tolerated 

VZV= Varicella‐zoster virus 

San Miguel, et al. N Engl J Med. 2008;359:906‐917. 

Harousseau, et al. J Clin Oncol. 2010;28(30):4621‐4629. 

Sonneveld, et al. Blood. 2008;112. Abstract 653. 

Vickrey E, et al. Cancer. 2009;15(1):229‐232. 

Chanan‐Khan A, et al. J Clin Oncol. 2008;26(29):4784‐4790. 

Question 

& 

Answer Session

New Drugs 2012 

Anna Nowobilski‐Vasilios 

PharmD MBA FASHP CNSC BCNSP 

Principal, Anovation Care Management Innovation 

Adjunct Assistant Professor, Midwestern University CCP 

This presentation is provided for educational purposes only. Consult product specific prescribing information prior to application in the clinical setting. 

Graphics sourced from Google Image are used for educational purposes and may be protected by copyright law (Title 17 U.S. Code) 

©2012, Anovation, Inc. All rights reserved. 

20 

New Druggs 

2012-H1 

Obesity: lorcaserin PO (BELVIQ) 

Actinic keratosis: ingenol mebutate TOP (PICATO) 

Glaucoma: tafluprost OP (ZIOPTAN) 

RDS: lucinactant ITR (SURFAXIN) 

Cystic Fibrosis: ivacaftor PO (KALYDECO) 

Pancreatitis: pancrelipase PO (ULTRESA; VIOKACE) 

Erectile Dysfunction: avanafil PO (STENDRA) 

Urinary Incontinence: mirabegron PO (MYRBETRIQ) 

Anemia of CKD: peginesatide IV/SC (OMONTYS) 

Cushing’s Syndrome: mifepristone PO (KORLYM) 

Gaucher Disease: taliglucerase IV (ELELYSO) 

MTX Toxicity: glucarpidase IV (VORAXAZE) 

Renal CA: axitinib PO (INLYTA) 

Basal Cell CA: vismodegib PO (ERIVEDGE) 

Breast CA: pertuzumab IV (PERJETA) 

Influenza Vaccine INH (FLUMIST Quadrivalent) 

N.meningitidis/H.flu Vaccine IM (MENHIBRIX) 

PET/Alzheimer’s: florbetapir F18 IV (AMYVID) 

Surgery: keratinocytes/fibroblasts TOP (GINTUIT) 

References: (1) fda.gov. (2) drugs.com. (3) Pharmacist’s Letter. 




lorcaserin 

BELVIQ® 

• 5‐HT2C agonist WITH diet/exercise 

– BMI ≥ 30 

– BMI ≥ 27 w/ HTN, DM2, or dyslipidemia 

• Thought to promote satiety … ↓ food intake 

• 3 RDBPC trials 52‐104 weeks, 8000 pts 

– 5% body wt loss: 47% vs 23% control w/o DM2; 

1/34 

3/34 

Approved 6/27/2012 

C PO 

Pregnancy 

Category X 

NOT FOR USE 

IN CHILDREN 

? 

Store at Controlled 

Room Temperature 

�� 

38% vs 16% control w/DM2 

– 8.5% vs. 6.7% control DC 2 o ADRs: HA, depression, dizziness 

• Caution: serotonin syndrome, valvular heart disease, 

cognition, depression, suicidal thoughts, priapism 

• Many DI’s: SSRIs, SNRs, MAOIs, St. John’s Wort, etc. 

• 10 mg PO BID � DC if body wt not ↓5% in 12w 

• Modestly effective 

References: (a) BELVIQ® (lorcaserin) [package insert]. Woodcliff Lake NJ: Eisai, Inc., June 2012. (b) FDA approves Belviq to treat some overweight or 

obese adults. FDA News. June 27, 2012. (c) Weight Loss. Pharmacist’s Letter 2012; 28:August. (d) Drugs for Weight Loss. Pharmacist’s Letter 2012; 

28(8):280811. (e) Micromedex v1535, Accessed 8/8/2012. 




CAUTION in Kidney/ 

Liver Dysfunction 

Do not use machinery or 

ddrive i until til effect ff t is i known k 

5/34 


Technicians: 

• Name the disease state and 

therapeutic class for select new 

agents approved during the first half 

of 2012. 

• Discuss the dosage form and route of 

administration for each new agent. 

• Describe the most serious adverse 

effects for each class of agent. 

• List special considerations related to 

storage, preparation, and dispensing 

for each new agent. 

Pharmacists: 

• Describe the therapeutic classification 

and indications for select new agents 

approved in the first half of 2012. 

• Discuss the dosing, administration, and 

appropriate role of each new agent. 

• List the major adverse effects, 

contraindications, and precautions for 

each new agent. 

• Discuss special considerations related 

to storage, preparation, dispensing, 

and monitoring each new agent. 

Disclosures: Speaker or spouse do not have actual or potential 

conflict of interest in relation to this presentation. 




General Wellbeing » Obesity 

• > 2/3 adults in US are overweight or obese 

• Substantial public health crisis 

• $100B annual cost of managing obesity 

• Risk of coronary heart disease 

– 1.72 @ BMI 25‐28.9 kg/m2 – 3.44 @ BMI > 33 kg/m2 • Similar ↑risk w/ stroke & HF 

• Goal: weight loss to optimal BMI 

• Treatment: diet, exercise, behavioral changes, anti‐ 

obesity medications … 

References: (a) Obesity. Emedicine.medscape.com. August 2, 2012. (b) FDA approves Belviq to treat some overweight or obese adults. FDA News. 

June 27, 2012. (c) Drugs for Weight Loss. Pharmacist’s Letter 2012; 28(8):280811. 




Self‐Assessment 1 

Which of the following is TRUE? 

1. 1/3 of the US population is overweight or 

obese. 

22. SSuccessful f lweight ihl loss programs rely l on anti‐ i 

obesity medications alone. 

3. Lorcaserin (BELVIQ) is modestly effective. 

4. Lorcaserin (BELVIQ) can safely be given in 

pregnancy. 




8/30/2012 

2/34 

4/34 

6/34 

1

Ophthalmology » Glaucoma 

• Optic nerve structural/functional 

disturbance 

– Possible with normal IOP 

– Ocular hypertension risk for glaucoma 

– Diverse condition 

• Second leading cause of blindness in US 

• Only 50% aware they have POAG 

• Goal – lower IOP or remove cause 

• Topical Options 

– beta‐blockers, carbonic anhydrase inhibitors, 

alpha‐2 agonists, cholinergic agonists 

– prostaglandin analogs … most widely used 

References: (a) Primary Open‐Angle Glaucoma. Emedicine.medscape.com. July 9, 2012. (b) FDA approves Zioptan to treat elevated eye pressure. 

FDA News. February 14, 2012. (c) Tafluprost (Zioptan) –A New Topical Prostaglandin for Glaucoma. The Medical Letter 2012; 54(1388):31. 





Which of the following statements is FALSE? 

1. Glaucoma is the 2nd leading cause of 

blindness in the US. 

22. Tafluprost (ZIOPTAN) is preservative preservative‐free free. 

3. In the pharmacy, tafluprost (ZIOPTAN) is 

stored in the refrigerator. 

4. Left‐over solution from opened tafluprost 

(ZIOPTAN) droppers can be saved for the 

following dose. 




lucinactant 

SURFAXIN® 

• Prevent of RDS in high risk premature infants 

– Compensates for surfactant deficiency 

• Trial w/ 1294 infants 

– ↓ RDS @24h & ↓ RDS mortality @ day 14 

• Watch oxygen/ventilator needs closely; suction if 

airway a ayobst obstruction uct o 

• NOT for ADULT RDS 2 o increased negative sequellae 

• 5.8 mL/kg birth weight intratracheally 

– Up to 4 doses in 1 st 48 hours of life, nmt that q6 hrs 

• Aseptic technique 

– Clinician competent in intubation, ventilator management, 

& premature infant care 

– Warm vial, shake vigorously until free‐flowing 

– If not used immediately protect from light at RT up to 2h 

Reference: SURFAXIN® (lucinactant) [package insert]. Warrington PA: Discovery Laboratories, Inc., March 2012. 




7/34 

9/34 


NOT FOR USE 

IN ADULTS 

iTR 

Keep in Refrigerator 

DO NOT FREEZE 

Once warmed: 

SHAKE WELL 

� 

PROTECT 

FROM LIGHT 

No Preservatives 

DISCARD unused portion 

11/34 

tafluprost 

ZIOPTAN 

• PF Prostaglandin analog to ↓ IOP in POAG or OH 

• Trial of 643 w/ OAG or OH, ↓ IOP to WNL in 12 wks 

– Non‐inferior to that with PF timolol eye gtts 

– Latanoprost slightly more effective than tafluprost in a 

preservative‐containing trial of 533 

• Warnings: hyperpigmentation, eyelash changes 

• Store in original pouch, refrigerated 

• Once pouch opened, use droppers within 28 days 

• 1 gtt QPM into conjunctival sac of affected eye(s) 

• Pt Ed: darkening of iris; darkening of eyelid; eyelash growth; 

aseptic technique; wait 5 min to instill another product 

• $97/month; generic latanoprost $23/month 

• Use for pts sensitive to preservatives 

References: (a) FDA approves Zioptan to treat elevated eye pressure. FDA News. February 14, 2012. (b) ZIOPTAN (tafluprost) [package 

insert]. Whitehouse Station NJ: Merck & Co., Inc., February 2012. (c) Tafluprost (Zioptan) –A New Topical Prostaglandin for Glaucoma. 

The Medical Letter 2012; 54(1388):31. (d) Glaucoma. Pharmacist’s Letter 2012; April(28). (e) Micromedex v1535, Accessed 8/8/2012. 




Pulmonology » RDS 

• Impaired surfactant synthesis 

in premature infants 

• 20,000‐30,000 newborns annually 

~ 50% born at 26‐28 w gestation 

< 30% born at 30‐31 w gestation 


8/30/2012 

OP 

Pregnancy 

Category C 

NOT FOR USE 

IN CHILDREN 


DO NOT FREEZE 

Once pouch opened: 



�� 

PROTECT FROM 

MOISTURE 

�No Preservatives 


Product 

Image 

• AAcute t CComplications li ti – alveolar l l rupture, t infection, i f ti intracranial i t i l 

hemorrhage, patent ductus arteriosus, pulmonary 

hemorrhage, necrotizing enterocolitis, apnea of prematurity 

• Chronic complications – bronchopulmonary dysplasia, 

retinopathy of prematurity, neurological impairment 

• Goal ‐ ↑ survival, ↓ severity of complica�ons 

• Treatment Options –antenatal steroids, resuscitation, gentle 

ventilation, supportive therapy … surfactant administration … 

Reference: Respiratory Distress Syndrome. Emedicine.medscape.com. March 9, 2012. 





Lucinactant (SURFAXIN) is … 

1. administered intratracheally using aseptic 

technique. 

22. warmed d and d shaken hk until il iit iis free‐flowing. 

f fl i 

3. stored in the refrigerator if not used 

immediately. 

4. 1 and 2 above are correct. 




8/34 

10/34 

12/34 

2

Pulmonology » Cystic Fibrosis 

• Autosomal recessive disorder 

• Defective CFTR gene 

– ↓ mucus hydra�on � sticky mucus 

– Increased viscosity of secretions in respiratory 

tract, pancreas, GI tract, sweat glands 

– Chronic lung disease & exocrine pancreatic 

insufficiencyy 

• Most common lethal inherited disease in 

Caucasians … 30,000 pts w/ CF in US 

• Median survival 40 years, M>F 

• Therapeutic Goals – maintain lung function; 

supplement enzymes, vitamins, minerals; 

manage complications 

• Treatment by multidisciplinary CF centers 

References: Cystic Fibrosis. Emedicine.medscape.com. May 15, 2012. 





Which of the following is FALSE about ivacaftor? 

1. It is the first drug to address the cause of 

Cystic Fibrosis. 

22. It will ill bbenefit fi 30 30,000 000 CF patients i iin the h US. S 

3. It enhances chloride transport. 

4. It improves lung function and decreases 

exacerbations. 




�� 

� 

Pregnancy 

Category C 



PROTECT FROM 

MOISTURE 

Take with 

FOOD 

pancrelipase 

ULTRESA and VIOKACE 

• 4th & 5th pancreatic enzyme products 

• Pork‐derived lipase, protease, amylases 

• Unapproved pancreatic enzyme sunset April 2010 

• NOT interchangeable 

• ULTRESA: EC delayed‐release capsule for CF 

– Trial 1 DBPC crossover, 24 pts, 8‐37yo w/ CF. CFA 89% 

vs 56%; CNA 84% vs 59% 

– Trial 22, 9 pts pts, 7‐11yo 7 11yo w/ CF. CF CFA 83% vs 35% 

13/34 

15/34 


Pregnancy 

Category C 

PO 

NOT FOR USE 

IN CHILDREN 



�� 

�� 

PROTECT FROM 

MOISTURE 

DO NOT 

CRUSH OR CHEW 

• 

– 2 Safety Trials: HA pharyngolaryngeal pain, nosebleed 

VIOKACE: uncoated tablet used w/ PPI for chronic 

pancreatitis 

Take with 

FOOD 

DO NOT 

CRUSH OR CHEW 

– RDBPC, 50 pts, 24‐70yo w/ EPI. CFA 86% vs 58% 

– 1 Safety Trial: biliary tract stones, anal pruritus 

• Caution: pork allergy, fibrosing colonopathy w/ hi‐ 

dose, caution in gout, renal impairment, 

hyperuricemia, theoretical risk of viral transmission. 

• Not absorbed in GIT 

References: (a) Exocrine Pancreatic Insufficiency. Emedicine.medscape.com. July 6, 2012. (b) ULTRESA (pancrelipase) [package insert]. Birmingham 

AL: Aptalis Pharma US, Inc., March 2012. (c) VIOKACE (pancrelipase) [package insert]. Birmingham AL: Aptalis Pharma US, Inc., March 2012. (d) (FDA) 

FDA approves two new pancreatic enzyme products to aid food digestion. FDA News. March 1, 2012. (e) (ML) In Brief: Pancreatic Enzyme Products. 

The Medical Letter 2012; 1357:12. (f) Gastroenterology. Pharmacist’s Letter 2012; 26:October. (g) Micromedex v1535, Accessed 8/8/2012. 




17/34 

ivacaftor 

KALYDECO 

• CFTR protein enhancer, ↑s chloride transport 

• 1st drug to address CAUSE 

• CF w/ G551D mutation (1,200 pts) 

• 48w RDBC in 161 > 12yo: 10.4% ↑FEV1 

– ↑ lung fxn, ↓ respiratory symptoms, ↑ wt gain 

– 33% vs 59% pulmonary l exacerbation b i 

• 48w RDBC in 52 6‐11yo: 12.5% ↑ FEV1� 

• ↑ LFTs; mul�ple CYP3A interac�ons 

• 150 mg PO q12h w/ high‐fat meal 

• Avoid grapefruit & Seville oranges 

• Monitor FEV1; LFTs q3m x1yr; then qYR 

• Limited Distribution; $294,000/year 

References: (a) KALYDECO (ivacaftor) [package insert]. Cambridge MA: Vertex Pharmaceuticals, Inc., January 2012. (b) Cystic Fibrosis. 

Pharmacist's Letter 20120; March 2012 (28). (c) Ivacaftor (Kalydeco) for Cystic Fibrosis. The Medical Letter 2012; 54(1388):29. (d) 

Micromedex v1535, Accessed 8/7/2012. 




Gastroenterology » EPI 

• Pancreatic enzyme deficiency 

– amylase, protease, lipase 

– Inability to digest food, esp. fatty food 

• Pancreatic causes: chronic pancreatitis, cystic 

fibrosis, pancreatic duct obstruction, SDS 

• 200,000 in US w/ pancreatic insufficiency 

• Steatorrhea, weight loss, watery diarrhea 

• Goal – facilitate food absorbtion 

• Treatment – lifestyle modification, vitamin 

supplementation, and … pancreatic enzyme 

replacement 


specialty 

medication 

8/30/2012 

PO 

Pregnancy 

Category B 

NOT FOR USE 

IN < 6 YO 



Take with 

Fatty Food 

� 

References: (a) Exocrine Pancreatic Insufficiency. Emedicine.medscape.com. July 6, 2012. (b) FDA approves two new pancreatic enzyme products to 

aid food digestion. FDA News. March 1, 2012. 





Which is the following is FALSE about the 

pancreatic enzymes approved in 2012? 

1. ULTRESA is a delayed‐release capsule. 

22. VIOKACE is indicated in children with 

pancreatic insufficiency due to CF. 

3. ULTRESA and VIOKACE should be protected 

from moisture. 

4. ULTRESA and VIOKACE are NOT 

interchangeable. 




14/34 

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18/34 

3

Urology » Overactive Bladder 

• Urgency & urinary incontinence 

• Voiding > 8x/24hrs 

• Underlying detrusor overactivity 

– Neurological, muscular, idiopathic 

• 33 M Americans w/ OAB 

• Impaired QOL: ↑depression, ↓sleep, 

↑nocturnal falls … coping strategies 

• Treatment Options: pharmacotherapy, 

behavioral therapy, surgery (rare) 

References: (a) Overactive Bladder. Emedicine.medscape.com. June 29, 2012. (b) FDA approves Myrbetriq for overactive bladder. FDA News. June 

28, 2012. 





Overactive Bladder (OAB) decreases QOL by: 

1. Increasing depression. 

2. Increasing coping strategies. 

3. Increasing nocturnal falls. 

4. All of the above. 




REMS 

peginesatide 

OMONTYS® 

• ESA for anemia of CKD in DIALYSIS only 

• Synthetic pegylated peptide, stimulates erythropoiesis 

• 2 Trials, 1626 HD pts, ≥52w, noninferior to epoetin re Hgb 

• Safety: 22.8% vs 24,4% death, stroke, MI, HF, unstable 

angina, arrhythmia 

• CI: uncontrolled HTN 

• RTU. Syringe & SDV PF. Discard MDV 28 days after 1st use. 

• Start at 0.04 mg/kg q MO IV or SC, adjust to Hgb 

• If no response in 12 wks, will most likely not respond 

• Monitor BP, Hgb, iron stores 

• Comparable S/E to epoetin in pts w/ ESRD on dialysis 

• Administered less frequently, less expensive 

• Long‐term safety data lacking 

19/34 

21/34 


IV/SC 

Pregnancy 

Category C 

NOT FOR USE 

IN CHILDREN 

DO NOT FREEZE 

� 

References: (a) OMONTYS (peginesatide) [package insert]. Deerfield IL: Takeda Pharmaceuticals, March 2012. (b) Peginesatide (Omontys) for Anemia 

in Chronic Kidney Disease. The Medical Letter 2012; 54(1392):45. (c) Micromedex v1535, Accessed 7/29/2012. 





DO NOT FREEZE 

PROTECT 

FROM LIGHT 

23/34 

mirabegron 

MYRBETRIQ 

• Beta‐3 agonist for OAB 

• Relaxes detrusor muscle to ↑ bladder capacity 

• 3 DBPCMC Trials, 4115 pts w/ OAB 

– ↓�mes urinated, ↓urina�on accidents, ↑ urine 

volume/void 

• 3 DBPC Trials, 2736 pts 

– most common ADRs for TX DC: nausea nausea, HA HA, HTN HTN, 

diarrhea, cons�pa�on, dizziness, ↑HR 

• Caution: ↑BP, an�muscarinic drugs, CYP2D6 

interactions, digoxin 

• Reduce dose in renal & hepatic impairment. 

• Don’t give in ESRD or severe hepatic impairment. 

• 25 mg po QD; may ↑ to 50 mg QD p/ 8 weeks. 

• Modestly effective & may increase BP 

References: (a) Overactive Bladder. Emedicine.medscape.com. June 29, 2012. (b) MYRBETRIQ (mirabegron) [package insert]. Northbrook IL: 

Astellas Pharma US, Inc., June 2012. (c) FDA approves Myrbetriq for overactive bladder. FDA News. June 28, 2012. (d) Overactive Bladder. 

Pharmacist’s Letter 2012; 28:May. (e) Micromedex v1535, Accessed 8/8/2012. 




Nephrology » Anemia of CKD 


8/30/2012 

PO 

Pregnancy 

Category C 

NOT FOR USE 

IN CHILDREN 



DO NOT 

CRUSH OR CHEW 

• Kidneys responsible for 90% of EPO 

production 

• EPO production deficiency in CKD 

• SStage III CKD, 5.2% 2% concurrent anemia i 

• Stage IV CKD, 44.1% concurrent anemia 

• M/M depends on underlying causes & stage 

• Options: ESA to Hgb 11‐12 g/dL 

Reference: Anemia of Chronic Disease and Renal Failure. Emedicine.medscape.com. May 1, 2012. 





Peginesatide (OMONTYS) is indicated for: 

1. Anemia of CKD in dialysis patients. 

2. Anemia of CKD in non‐dialysis patients. 

3. Anemia of chronic disease, including cancer. 





20/34 

22/34 

24/34 

4

Oncology » MTX Toxicity 

• MTX 1o kidney excretion 

• High dose 

– nephrotoxicity 

– Bone marrow suppression 

– Oral/GI ulceration 

– Liver toxicity 

• Goal: Reduce toxicity 

• Options: leucovorin, IV hydration, 

urine alkalinization … & … 

Reference: The Medical Letter 2012; 1385:19. 





Glucarpidase (VORAXAZE) 

1. Is a monoclonal antibody that lowers toxic 

methotrexate concentrations. 

22. Is usually ll well ll tolerated, l d but b can cause 

serious anaphylactic reactions. 

3. Can be stored for 24 hours after 

reconstitution, if refrigerated. 





pertuzumab 

PERJETA 

• Recombinant humanized mAb against HER2 receptor 

• Combo w/ trastuzumab and docetaxel for HER2+ 

metastatic breast CA w/o prior metastatic tx; different 

binding site than trastuzumab 

• RMCDBPC Trial (CLEOPATRA), 808 pts” +6.1 mo PFS 

• Safety endpoints: febrile neutropenia, ↓sLVEF 

• 840 mg over 60 min i IV IV, then h 420mg 420 over 30‐60 30 60 min i q3w 3 

• Modify dose for delayed/missed doses, LVEF < 40%, 

trastuzumab hold/DC 

• Observe pt 60 min p/ #1, 30 min p/ subsequent infusions 

• Dilute in 250 mL NS, refrigerate x 24h –do NOT use D5W 

• Pt Ed: pregnancy prevention, pregnancy registry 

• HER2 status, pregnancy test, LVEF q3m, infusion 

reactions 

• $4075/vial 

References: (a) PERJETA (pertuzumab) [package insert]. South San Francisco CA: Genentech, Inc., May 2012. (b) Pertuzumab (Perjeta) for 

HER2‐Positive Metastatic Breast Cancer. The Medical Letter 2012; 54(13950:59. (c) Micromedex v1535, Accessed 8/7/2012. 




25/34 

27/34 


Pregnancy 

Category D 

IV 

NOT FOR USE 

IN CHILDREN 


DO NOT FREEZE 

Mix Gently 

DO NOT SHAKE 

PROTECT 

�� 

FROM LIGHT 



29/34 

glucarpidase 

VORAXAZE® 

• Recombinant enzyme for toxic [MTX] 

– Converts to glutamate & DAMPA 

• 2 unpublished (PI) single‐arm, open‐label studies 

– Endpt: RSCIR [MTX] < 1 mcmol @ 15 min x 8 days; > 95% 

↓[MTX] 

– Safety data available for 290 pts; only 22 evaluated for 

efficacy 

• ADRs –rare serious allergic reactions; generally well 

tolerated 

• Continue leukovorin (not w/in 2h) & 

hydration/alkalinization 

• Preparation: reconstitute w/ 1 mL SWI; use w/in 4h if 

Refrig 

• Dose: 50 units/kg IV bolus over 5 minutes 

• Monitor: [MTX] normalization 

References: (a) VORAXAZE® (glucarpidase) [package insert]. West Conshohocken PA: BTG International, Inc.; January 2012. (b) The Medical Letter 

2012; 1385:19. (c) Micromedex v1534, Accessed 7/27/2012. 




Oncology » Breast Cancer 


Pregnancy 

Category C 

8/30/2012 

IV 


DO NOT FREEZE 



• HER2 overexpression in 20% of breast cancers 

• More aggressive, worse prognosis before HER2‐ 

targeted therapies (trastuzumab) 

• After 20 yrs of increasing incidence, now decreasing 

– Reduced use of HRT 

• 207,090 new F cases/yr in US (2010), 1970 new M 

• 39,840 F deaths in US (2010), 390 M deaths 

• Treatment Options; surgery for early‐stage, adjuvant 

therapy for micrometastasis. 

• HER2‐targeted therapies: trastuzumab, lapatinib … 

now … pertuzumab 

Reference: Breast Cancer. Emedicine.medscape.com. August 1, 2012. 





Pertuzumab (PERJETA) … 

1. Is a recombinant monoclonal antibody 

against the HER2 receptor. 

22. Fits i on a diff different HER2 2 bi binding di site i than h 

trastuzumab (HERCEPTIN). 

3. Should not be diluted into D5W. 





26/34 

28/34 

30/34 

5

Infectious Disease » Vaccine 

• N. meningitidis (C&Y) and H. influenza type b 

• Early symptoms indistinguishable from other 

childhood illnesses 

• N. meningitis prevalence 1‐2 / 100,000 

• Hib incidence ↓d by 99% since vaccine (1988) 

• Fulminant meningococcemia fatal w/o ABs; 

50% mortality w/ ABs 

• Hib meningitis mortality 5%; 50% neurologic 

sequelae; 6% permanent hearing loss 

References: (a) Meningococcal Infections. Emedicine.medscape.com. October 17, 2011. (b) Haemophilus Influenzae Infections. 

Emedicine.medscape.com. January 10, 2012. (c) FDA approves new combination vaccine that protects children against two bacterial diseases. FDA 

News. June 14, 2012. 





The new N. meningitidis‐H. influenzae Vaccine 

(MENHIBRIX) is indicated for use in … 

1. infants < 6 weeks old. 

22. children hild from f 6 weeks k to 19 9 months. h 

3. Adults. 





31/34 

33/34 

N. meningitidis‐H. influenzae Vaccine 

MENHIBRIX® 

• Combo vaccine for 6w to 18 mos 

• Active immunization to prevent Neisseria meningitidis 

serogroups C and Y and Haemophilus influenzae type b 

• 6 Trials; 7,521 infants, antibody response predictive of 

protection 

• Safety trials; 7,500 infants; ADRs: pain, redness and 

swelling lli at t the th injection i j ti site, it irritability i it bilit and d fever f 

• Guillain‐Barré (weigh continuation), fainting, apnea 

(preemies) 

• Probable interaction w/ live measles virus vaccine 

• 0.5mL IM at 2, 4, 6, and 12‐15 mos old. First as early as 

6 weeks, 4 th as late as 18 mos. 

• Administer immediately after reconstitution w/ diluent 

• Do not mix with other vaccines is same syringe or vial 

References: (a) MENHIBRIX (Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine) [package insert]. Research Triangle 

Park NC: GlaxoSmithKline, June 2012. (b) FDA approves new combination vaccine that protects children against two bacterial diseases. FDA News. 

June 14, 2012. (c) Micromedex v1535, Accessed 8/8/2012. 




7 

General Wellbeing 

Dermatology 

Ophthalmology 

Otolaryngology 

Cardiology 

Pulmonology 

Gastroenterology 

Urology 

Nephrology 

Obstetrics/Gynecology 

Neurology gy 

Psychiatry 

Rheumatology 

Immunology 

Endocrinology 

Metabolic Disease 

Hematology 

Oncology 

Infectious Disease 

Radiology 

Other 

New Druggs 

2012-H2 

VIS 


8/30/2012 

IM 

Pregnancy 

Category C 

NOT FOR USE 

IN < 6wo or >19mo 

NOT FOR USE 

IN ADULTS 


or Room Temp 

DO NOT FREEZE 

Obesity: phentermine/topiramate PO (QSYMIA) 

Hypertriglyceridemia: icosapent PO (VASCEPA) 

COPD: aclidinium bromide INH (TUDORZA) 

Colonoscopy Prep: sodium picosulfate/ 

magnesium oxide/citric acid PO (PREPOPIK) 

Multiple myeloma: carfilzomib IV (KYPROLIS) 

(Ph‐) ALL: vinCRIStine liposome IV (MARQIBO) 

Colon Cancer: ziv‐aflibercept IV (ZALTRAP) 

(as of 08/09/12) 

QUESTIONS? 

annanv@anovation.us 

References: (1) fda.gov. (2) drugs.com. (3) Pharmacist’s Letter. 




32/34 

34/34 

6

NEW DRUGS AND BIOLOGICALS 2012 

RESOURCE LIST 

Specialty Generic Name Brand Name Company Rte Class & Indication Approval 

Oncology glucarpidase VORAXAZE BTG 

International 

IV Carbiztoeotudase for the treatment of toxic plasma methotrexate 

concentrations in patient with delayed methotrexate clearance due to 

impired renal function. 

1/17/2012 

Oncology axitinib INLYTA Pfizer PO Kinase inhibor for advanced renal cell cancer after failure of one prior 

systemic therapy. 

1/27/2012 

Oncology vismodegib ERIVEDGE Genentech PO Hedgehog pathway inhibitor for adult metastatic basal cell carinoma. 1/30/2012 

Pulmonology ivacaftor KALYDECO Vertex PO Cystic fibrosis trnasmembrance conductance regulator (CFTR) for the 

treatment of cystic fibrosis (CF) in patients 6 years old and older who 

have a G551D mutation in the CFTR gene. 

1/31/2012 

Dermatology ingenolmebutate PICATO Leo Pharma TOP Topical gel for actinic keratosis 1/23/2012 

Opthalmology tafluprost ZIOPTAN MSD OP Prostaglandin analog for reducing elevated intraocular pressure in openangle 

glaucoma or ocular hypertension. 

2/10/2012 

Endocrinology mifepristone KORLYM Corcept PO cortisol receptor blocker for hyperglycemia secondary to hypercortisolism 2/17/2012 

Therapeutics in adult patients with endogenous Cushing's syndrome who have type 2 

diabetes mellitus or glucose intolerance and have failed surgery or are 

not candidates for surgery 

Infectious quadrivalent FLUMIST MedImmune INH Vaccine to prevent seasonal influenza in people ages 2-49yo. Contains 2/29/2012 

Diseases influenza 

vaccine 

Quadrivalent 

four influenza strains (2 A and 2 B) 

Gastroenterology pancrelipase ULTRESA Aptalis Pharma PO Delayed-release capsule for children and adults with cystic fibrosis who 

cannot digest food normally because their pancreas does not make 

enough pancreatic enzymes 

3/1/2012 

Gastroenterology pancrelipase VIOKACE Aptalis Pharma PO In combination with a proton pump inhibitor for adults with chronic 

pancreatitis who cannot digest food normally. 

3/1/2012 

Pulmonology lucinactant SURFAXIN Discovery Labs ITR intratracheal suspension for the prevention of respiratory distress 

syndrome (RDS) in premature infants at high risk of RDS 

3/6/2012 

Surgery keratinocytes GINTUIT Organogenesis TOP allogeneic cellularized scaffold product indicated for topical (non- 3/9/2012 

and fibroblasts in 

submerged) application to a surgically created vascular wound bed in the 

bovine collagen 

treatment of mucogingival conditions in adults 

Nephrology peginesatide OMONTYS Affymax IV-SQ erythropoiesis-stimulating agent (ESA) for the treatment of anemia due 

to chronic kidney disease (CKD) in adult patients on dialysis 

Radiology Florbetapir F18 AMYVID Avid IV radioactive diagnostic agent for Positron Emission Tomography (PET) 

Radiopharmace imaging of the brain to estimate β-amyloid neuritic plaque density in 

uticals 

adult patients with cognitive impairment who are being evaluated for 

Alzheimer’s Disease (AD) and other causes of cognitive decline 

NOTE: This chart is provided for reference purposes only. Product specific prescribing information (see Brand Name links) should be consulted prior to application in the clinical setting. 1 of 2 

3/27/2012 

4/6/2012

NEW DRUGS AND BIOLOGICALS 2012 

RESOURCE LIST 

Specialty Generic Name Brand Name Company Rte Class & Indication Approval 

Urology avanafil STENDRA Vivus PO phosphodiesterase 5 (PDE5) inhibitor indicated for the treatment of 

erectile dysfunction 

4/27/2012 

Metabolic taliglucerase alfa ELELYSO Pfizer / Protalix IV hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long- 5/1/2012 

Disease 

Bio 

term enzyme replacement therapy (ERT) for adults with a confirmed 

Therapeutics diagnosis of Type 1 Gaucher disease. 

Oncology pertuzumab PERJETA Genentech IV HER2/neu receptor antagonist indicated in combination with trastuzumab 

and docetaxel for the treatment of patients with HER2-positive 

metastatic breast cancer who have not received prior anti-HER2 therapy 

or chemotherapy for metastatic disease 

6/8/2012 

Infectious meningitis & MENHIBRIX Glaxo Smith IM Active immunization to prevent invasive disease caused by Neisseria 6/14/2012 

Diseases haemophilus 

Kline 

meningitidis serogroups C and Y and Haemophilus influenzae type b. 

influenzae 

MENHIBRIX is approved for use in children 6 weeks of age through 18 

vaccine 

months of age 

General lorcaserin BELVIQ Eisai PO Serotonin 2C receptor agonist as an adjunct to a reduced-calorie diet and 6/27/2012 

Wellbeing hydrochloride 

exercise, for chronic weight management in adults with an initial BMI > 

30kg/m2 or BMI > 27kg/m2 with one weight-related co-morbid condition. 

Urology mirabegron MYRBETRIQ Astellas PO Beta-3 adrenergic agonist indicated for the treatment of overactive 

bladder (OAB) with symptoms of urge urinary incontinence, urgency, and 

urinary frequency. 

Sources: Pharmacist’s Letter; FDA.gov; drugs.com; manufacturer websites 20 

Provided as a professional courtesy by: 

1006 South Michigan Avenue, Suite 702 | Chicago Illinois 60605 | 312-608-1495 tel | 312-268-5112 fax | www.anovation.us 

NOTE: This chart is provided for reference purposes only. Product specific prescribing information (see Brand Name links) should be consulted prior to application in the clinical setting. 2 of 2 

6/28/2012

Disease State Reviews for Pharmacy Technicians 

Bugs and Drugs 101: A Review of 

Infectious Diseases for Technicians 

Nicole Costa, PharmD 


*The speaker has no actual or potential conflict of interest in relation to this activity. 

Urinary Tract Infections (UTI) 1,2 

• Usually young females 

• Symptoms: 

– Urgency 

– Frequency 

– Painful urination 

– No fever 

– Normal white blood cell count 

• E. coli is the most common bacteria 

• Treatment options include SMX/TMP or 

ciprofloxacin 

Pyelonephritis 2 

• Upper UTI involving kidneys 

• More serious infection 

• Symptoms: 

– Fever/chills 

– Flank/abdominal pain 

– Nausea/vomiting 

• Need to treat with IV antibiotics until 

symptoms improve 

– Ciprofloxacin, ceftriaxone, pip/tazo 


• Identify common bacterial infections that 

occur in the acute care setting. 

• Discuss appropriate antibiotic therapy 

regimens for treating infections using 

evidence‐based recommendations. 

• Discuss the technician’s role in assessing the 

appropriateness of antibiotic use within an 

acute care setting. 

Complicated Urinary Tract Infections 3 

• Can occur in: 

– Men 

– Pregnant women 

– Patients from a hospital/nursing home 

– People who use catheters 

• Symptoms: 

– Fever 

– Elevated white blood cell count 

– Altered mental status 

• Treatment options include ciprofloxacin, ceftriaxone, 

or piperacillin/tazobactam 

Case Study 

• GB is a 76 year old female who resides in a 

nursing home. She is admitted to the hospital 

with a temperature of 102, altered mental 

status status, nausea nausea, and left flank pain pain. 

• GB most likely has which of the following 

conditions: 

A) uncomplicated UTI 

B) complicated UTI 

C) pyelonephritis 

8/29/2012 

1

Cellulitis 4,5 

• Bacterial infection of the outer skin levels as well as the 

deeper fat layers 

• Symptoms: 

– Redness 

– Warm feeling skin 

– Inflammation 

– Pain 

• Staph aureus is the most common bacteria 

• Treatment options: 

– Cephalexin (not MRSA), clindamycin, SMX/TMP, doxycycline 

Case Study 

• AR is a 17 year old male who wrestles on his high 

school team. He noticed what looked like a 

spider bite on his arm 1 week ago, and now his 

whole forearm is red, , swollen, , and painful. p He 

goes to his doctor and is diagnosed with cellulitis. 

• Which bacteria is most likely the cause of AR’s 

infection? 

A) E.coli B) Pseudomonas 

C) Klebsiella D) MRSA 

Sinusitis 8 

• Inflammation of the sinuses 

• May be caused by infection, allergy, or 

autoimmune disease 

• Symptoms: 

– Nasal l congestion and d discharge d h 

– Loss of smell 

– Pressure‐like pain/facial tenderness 

• Most cases are caused by viruses 

• If symptoms last > 10 days, may be bacterial 

– Amoxicillin is the drug of choice 

Diabetic Foot Infections 6 

• Decreased blood flow to the feet 

�less oxygen 

�ideal for bacteria that survive without oxygen 

• Infections are caused by multiple different bacteria 

• Treat with broad spectrum antibiotics 

• Treatment options: 

– Piperacillin/tazobactam 

– Clindamycin + levofloxacin 

• Can progress to osteomyelitis (infection of bone) if 

left untreated 

Pharyngitis (“strep throat”) 7 

• Inflammation of the throat 

• Symptoms: 

– Fever 

– SSwollen ll llymph hglands l d 

– White exudate on tonsils 

– Sore throat/difficulty swallowing 

• Less than 30% caused by the bacteria 

Streptococcus pyogenes 

• Most commonly caused by viruses 

Acute Bronchitis 9 

• Inflammation of the lungs 

• Symptoms: 

– Cough 

Sh f b h 

– Shortness of breath 

– Sputum (phlegm) 

• Usually caused by a virus 

• Typically not treated with antibiotics 

8/29/2012 

2

Chronic Obstructive Pulmonary 

Disease (COPD) 10 

• Airflow limitation that is not fully reversible 

(chronic bronchitis) 

• Primarily caused by cigarette smoking 

• COPD exacerbation symptoms: 

– Change in baseline cough, shortness of breath, or 

sputum production 

• Treat with antibiotics depending on severity of 

exacerbation 

– Azithromycin, amoxicillin/clavulanate, levofloxacin 

Case Study 

• PR is a 57 year old male who has been smoking 2 

packs of cigarettes per day for the past 40 years. He 

normally has a dry cough and shortness of breath on 

exertion. PR decides to go to the doctor because he 

hhas been b coughing hi more with ith a lot l tof f sputum t and d 

can barely breath even when he is resting. 

• PR is most likely suffering from: 

A) Acute bronchitis B) COPD exacerbation 

C) Pneumonia D) Pharyngitis 

Case Study 

• LM is a 48 year old female who has been 

taking clindamycin for 1 week to treat a 

cellulitis infection. She develops abdominal 

cramping and is having diarrhea up to 7 times 

per day. She is diagnosed with C. diff colitis. 

• An appropriate antibiotic for the treatment of 

LM’s C. diff infection is: 

A) Levofloxacin B) Metronidazole 

C) Cephalexin D) Amoxicillin 

Pneumonia (PNA) 11 

• Inflammatory condition of the lung 

• Can be caused by bacteria, viruses, fungi, or parasites 

– Strep pneumo causes up to 50% of community‐acquired PNA 

• Symptoms: 

– Cough/chest pain 

– Fever 

– Difficulty breathing 

• Community‐acquired 

– Levofloxacin or azithromycin (+ ceftriaxone in hospital) 

• Hospital‐acquired 

– Pip/tazo + azithromycin or levofloxacin 

Pseudomembranous Colitis 12 

• Caused by the bacteria Clostridium difficile 

– Commonly known as C. diff 

• Usually a side effect of being on antibiotics 

• Symptoms: 

– Watery diarrhea > 3 times per day 

– Abdominal cramping 

– Blood in stool in severe infections 

• Treatments include metronidazole or oral 

vancomycin 

Technician’s Role 

• Clinical technicians can be a huge asset to 

pharmacists in the acute care setting 

• Assist in data collection 

– TTemperature t 

– White blood cell count 

– Culture monitoring 

– Appropriate dosing 

– Changing from IV to oral antibiotics 

8/29/2012 

3

References 

1. U.S. National Library of Medicine. Urinary Tract Infections‐Adults. Available at: 

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001549/. Accessed July 22, 2012. 

2. Gupta D, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated 

Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European 

Society for Microbiology and Infectious Diseases. Clin Infect Dis. (2011) 52 (5): e103‐e120. 

3. Hooton T, Bradley S, Cardenes DD, et al. Diagnosis, Prevention, and Treatment of Catheter‐Associated Urinary Tract 

Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin 

Infect Dis. (2010) 50 (5): 625‐663. 

4. U.S. National Library of Medicine. Cellulitis. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001858/. 

Accessed July 22,2012. 

5. Stevens DL, Bisno AL, Chambers HF, et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft‐Tissue 

Infections. Clin Infect Dis. (2005) 41 (10): 1373‐1406. 

6. Lipsky BA, Berendt AR, Cornia PB, et al. 2012 Infectious Diseases Society of America Clinical Practice Guideline for the 

Diagnosis g and Treatment of Diabetic Foot Infections. Clin Infect f Dis. (2012) ( ) 54 ( (12): ) e132‐e173. 

7. Bisno AL, Gerber MA, Gwaltney JM, et al. Practice Guidelines for the Diagnosis and Management of Group A Streptococcal 

Pharyngitis. Clin Infect Dis. (2002) 35 (2): 113‐125. 

8. U.S. National Library of Medicine. Sinusitis. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001858/. 


9. U.S. National Library of Medicine. Bronchitis. Available at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002078/. 

Accessed July 27, 21012. 

10. U.S. National Library of Medicine. Chronic Obstructive Pulmonary Disease. Available at: 

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001153/. Accessed July 27, 2012. 

11. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society Consensus 

Guidelines on the Management of Community‐Acquired Pneumonia in Adults. Clin Infect Dis. (2007) 44 (Supplement 2): 

S27‐S72. 

12. Cohen SH, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 

Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America 

(IDSA). Infection Control and Hospital Epidemiology , Vol. 31, No. 5 (May 2010), pp. 431‐455 

Questions? 

8/29/2012 

4


Catch Your Breath: Catch Up on the 

Latest in Asthma Education 

Jennifer Arnoldi Arnoldi, PharmD PharmD, BCPS 

ICHP Annual Meeting 


I have no conflicts of interest to disclose. 

Objectives 

• List at least three triggers that could lead to an 

asthma attack. 

• List the common asthma medications. 

• Describe ib the h phases h of f an asthma h action i plan. l 

Asthma 

• Chronic inflammatory airway disorder 

• Patient complaints 

– Wheezing and breathlessness 

– CCough h 

– Chest tightness 

• Especially at night or early morning 

Kelly HW and Sorkness CA. Asthma. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. 

New York, NY: McGraw-Hill; 2011:439-470. 

• Objectives 

• Asthma review 

• Asthma treatment 

• Asthma action plan 

• Summary 

• Questions 

Outline 

Introduction 

• 23 million Americans live with asthma 

• Asthma’s annual toll 

– 10.6 million doctor’s appointments 

– 11.7 million illi trips i to the h emergency room 

– 10.1 million missed work days 

– 12.8 million missed school days 

– 444,000 hospitalizations 

– 3,613 deaths 

National Asthma Control Initiative Action Guide. (NIH Publication 10-7542). Bethesda, MD: September 2010. U.S. Department of Health and Human Services. National 

Institutes of Health. National Heart, Lung, and Blood Institute. 

Characteristics of Asthma 

• Symptoms are reversible with proper 

treatment 

• Symptoms can be triggered 

– All Allergens 

– Irritants 

– Cold air 

– Certain medications 



8/30/2012 

1

Inhaled Medications for Asthma 

• Steroids 

– Examples: fluticasone, budesonide, mometasone 

– Reduce swelling / inflammation in the airways 

• Beta‐agonists 

Beta agonists 

– Example: albuterol and levalbuterol 

– Open up airways 

• Anticholinergics 

– Example: ipratropium and tiotropium 

– Relax airways and decrease secretions 

PL Technician Training Tutorial, Dispensing Inhalers. Pharmacist's Letter 2012; 28(2):280230 

Types of Inhalers 

Metered Dose Inhalers (MDI) Dry Powder Inhalers (DPI) 

Usually “L” shaped Usually disk or tube shaped 

Chemical propels medication from canister Inhaler contains powder that patient 

forcibly inhales into lungs 

Patients need good “inhaler technique” Some require insertion of capsule 

Long, slow breath Quick & forceful breath 

May be used with spacer devices No spacer is needed 

Must be “primed” before first use or if not 

used for a few days 

Does not require priming 

Must be shaken well before using Does not require shaking 

Mouthpiece should be cleaned with water May clean mouthpiece with dry tissue 

Tips for Correct Use of Inhalers. Pharmacist's Letter 2008; 24(4):240406 

Using a Peak Flow Meter 

• Patient blows a fast, hard breath into the 

mouthpiece 

• Patient records the score shown on the meter 

• Repeat twice 

• Best of three scores is ‘peak flow rate’ 

• Can be done daily for a few weeks to find 

‘personal best’ 



Why Did Some Inhalers Change? 

• Chlorofluorocarbons (CFCs) 

– Chemical to propel medication from the inhaler 

– Now banned for environmental reasons 

– Inhalers aesc changed a gedto to use HFAs s (hydrofluoroalkanes) 

( yd o uo oa a es) 

• Combivent® (albuterol and ipratropium) 

– Still contains CFC 

– Will be phased out by the end of 2013 and 

replaced with Combivent Respimat® 

PL Technician Training Tutorial, Dispensing Inhalers. Pharmacist's Letter 2012; 28(2):280230 

Peak Flow 

• Peak flow meter device measures how well 

the patient’s lungs are working 

• Helpful for: 

– MMonitoring it i day‐to‐day d t d breathing b thi changes h 

– Tracking asthma control 

– Recognizing a flare‐up 

– Deciding when to call the doctor or go to the 

emergency department 



Asthma Action Plan 

• Treatment plan based on patient’s symptoms 

or peak flow measurements 


– GGreen 

– Yellow 

– Red 

• Treatment recommendations based on 

category 

Asthma Action Plan. (NIH Publication No. 07-5251). Bethesda, MD: April 2007. U.S. Department of Health and Human Services. National Institutes of Health. National 

Heart, Lung, and Blood Institute. 

8/30/2012 

2

Green Zone 

• Patient is not having symptoms 

• Patient can do usual activities 

• Patient should take regular medications as 

prescribed p 



Red Zone 

• Patient is very symptomatic 

• Patient may have progressed to this stage 

from the Yellow Zone 

• Patient needs to use high doses of quick‐relief 

medicine and call his/her doctor or go to the 

hospital 



Yellow Zone 

• Patient is having symptoms or waking up at 

night due to asthma 

– Asthma symptoms may limit patient’s ability to do 

some activities 

• Pti Patient tneeds d tto use quick‐relief ik li f medicine di i 



References 

1. National Asthma Control Initiative Action Guide. (NIH Publication 10‐ 

7542). Bethesda, MD: September 2010. U.S. Department of Health and 

Human Services. National Institutes of Health. National Heart, Lung, and 

Blood Institute. 

2. Kelly HW and Sorkness CA. Asthma. In: DiPiro JT, Talbert RL, Yee GC, 

Matzke GR, GR Wells BG, BG Posey LM, LM eds. eds Pharmacotherapy: A 

Pathophysiologic Approach. 8th ed. New York, NY: McGraw‐Hill; 

2011:439‐470. 

3. PL Technician Training Tutorial, Dispensing Inhalers. Pharmacist's Letter 

2012; 28(2):280230 

4. Tips for Correct Use of Inhalers. Pharmacist's Letter 2008; 24(4):240406 

5. Asthma Action Plan. (NIH Publication No. 07‐5251). Bethesda, MD: April 

2007. U.S. Department of Health and Human Services. National 

Institutes of Health. National Heart, Lung, and Blood Institute. 

Questions Post Test Question 

1. Which of the following asthma medications is 

a beta‐agonist? 

a. Albuterol 

b Fluticasone 

b. Fluticasone 

c. Tiotropium 

d. Budesonide 

8/30/2012 

3


2. True or False. All patients with asthma have 

the same triggers for an asthma attack. 

a. True 

bb. False 

8/30/2012 

4


The Sweet Life: Recognizing the 

Signs and Symptoms of Diabetes 

and the Common Challenges of 

Diabetes b Management 

Ryan Birk 

PharmD Candidate 2013 

Southern Illinois University Edwardsville School of 

Pharmacy 

Objectives 

• Recognize common signs and symptoms of 

diabetes 

• Describe the differences in insulin onset and 

duration 

• Define common challenges for diabetes 

patients 

County‐level Estimates of Diagnosed 

Diabetes among Adults aged ≥ 20 years: 

United States 2009 

Centers for Disease Control and Prevention: National Diabetes Surveillance System. 

Available online at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Retrieved 8/17/2012. 

Percent 

0 - 6.5 

6.6 - 8.0 

8.1 - 9.4 

9.5 - 11.1 

> 11.2 


• The speaker has no conflicts to disclose. 

Future of Diabetes Mellitus 

• Currently 25.8 million individuals have 

diabetes (8.3 % of the U.S. population) 

• Estimated 7.0 million individuals are 

undiagnosed 

• $174 billion in total cost for diabetes care each 

year 

Prevalence 

Obesity (BMI ≥30 kg/m2 ) 

1994 2000 2010 

No Data

Defining Diabetes Mellitus 

• Diabetes mellitus is a group of metabolic 

disorders of fat, carbohydrate, and protein 

metabolism that results from a defect in 

insulin secretion secretion, insulin action (sensitivity), 

(sensitivity) 

or both. 

Type 1 vs. Type 2 Diabetes 

Type 1 Type 2 

Percentage of 

patients 

5%–10% ~90% 

Typical age at onset 40 yr 

Typical presentation Acute symptoms; May not be 

at diagnosis markedly elevated 

blood glucose 

diagnosed until 

complications appear 

Obesity Uncommon Very common 

Treatment Insulin Lifestyle changes and 

pharmacotherapy 

Diabetic ketoacidosis Often present Rare 

Which is a sign or symptom of 

diabetes? 

1. Decreased blood 

pressure 

2. Increased blood 

pressure 

3. Night time urinations 

4. Does not finish meals 

9 

Types of Diabetes 

• Type 1 diabetes 

– Patients do not produce insulin 

• TType 2 di diabetes b t 

– Patients do not produce enough insulin or the 

cells ignore insulin (cell sensitivity) 

Common Signs and Symptoms 

• Frequent urination 

• Uncontrolled thirst 

• Extreme hunger 

• Blurred vision or 

drowsiness 

• Frequent infections 

Insulin Therapy 

8/29/2012 

2

• A hormone produced by 

the pancreas 

• Central to regulating 

metabolism in the body 

– Signals the liver, muscle, 

and fat tissues to take up 

glucose from the blood 

What is Insulin? 

How to Classify Insulin 

Insulin Type Generic 

Names 

Rapid‐acting lispro, aspart, 

glulisine 

Regular or Short‐ 

acting 

Intermediate‐ 

acting 

Brand 

Names 

Humalog, 

Novolog, Apidra 

regular (R) Humulin R, 

Novolin R 

NPH (N), detemir Humulin N, 

Novolin N, 

Levemir 

Long‐acting glargine Lantus 

Differences in Insulin 

Rapid-acting 

Regular or Short-acting 

Intermediate-acting 

Long-acting 

How to Classify Insulin 

• Difference types of insulin: 

– Rapid‐acting 

– Regular or Short‐acting 

– Intermediate Intermediate‐acting acting 

– Long‐acting 

• Each insulin has 3 characteristics: 

– Onset 

– Peak time 

– Duration 

Differences in Insulin 

Insulin Type Onset Peak 

time 

Duration 

Rapid‐acting 5 minutes 1 hour 2 to 4 hours 

Regular or 

Short‐acting 

30 minutes 2 to 3 hours 3 to 6 hours 

Intermediate 

‐acting 

2 to 4 

hours 

Long‐acting 6 to 10 

hours 

4 to 12 

hours 

Theoretically 

should not 

peak 

12 to 18 

hours 

20 to 24 

hours 

What is the onset of regular (R) insulin 

after administering it to a patient? 

1. 5 minutes 

2. 30 minutes 

3. 60 minutes 

4. 90 minutes 

8/29/2012 

3

Common Challenges for Patients 

with Diabetes 

• Microvascular 

– Eye Complications 

– Kidney Complications 

– Nerve Damage (Neuropathy) 

• Macrovascular 

– Weight gain 

• Typically increases when started on insulin 

– Foot Complications 

– Heart and Brain Complications 

Which of the conditions below is an 

emergency complication/challenge? 

1. Nerve damage 

2. Weight gain 

3. Foot Complications 

4. Ketoacidosis 

References 

1. Diabetes.org [Internet]. Alexandria: American Diabetes Association; 

c1995‐2012 [updated 2012 May 16; cited 2012 Aug 13]. Available 

from: http://www.diabetes.org/. 

2. CDC.gov [Internet]. Atlanta: Centers for Disease Control and Prevention; 

[updated 2012 Feb 16; cited 2012 Aug 13]. Available from: 

http://www http://www.cdc.gov/. cdc gov/ 

3. American Diabetes Association. Standards of medical care in diabetes. 

Diabetes Care 2012;35;S11‐S63. 

4. Dipiro J, Talbert B, Yee GC, Matzke GR, Wells BG, Posey LM, editors. 

Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: 

McGraw‐Hill; 2008. 

5. Kitabchi A, Rose B. Treatment of diabetic ketoacidosis and hyperosmolar 

hyperglycemic state in adults. UpToDate. Waltham; 2012. 

Common Challenges for Patients 

with Diabetes 

• Emergency Complication 

– Ketoacidosis 

• Body starts burning fat for energy instead of glucose 

• Possible cause is failure to treat high blood glucose 

• Serous condition that can lead to coma or even death 

• Treatment: 

– Intravenous regular insulin 

– Lower Blood Glucose (Hypoglycemia) 

• Treatment: 

– Glucagon injection 

Questions? 

8/29/2012 

4

Unraveling Unraveling The The Puzzle Puzzle of of 

Substance Substance Abuse Abuse and and 

Chemical Chemical Dependency 

Dependency 

Within Within Pharmacy 

Pharmacy 

Wally Cross, RPh, MHS, CADC 

Resurrection Behavioral Health – 

Professionals Program 

847 493 3519 

wcross@reshealthcare.org 

The speaker has no conflict of interest to disclose. 

What What we we will will cover cover 

• Addiction 101 –basic facts about addiction 

• Statistics regarding addiction 

• Issues associated with addictive disease in 

pharmacists 

• Observable signs of addiction 

• How to help a colleague or patient with 

addiction 

• Prescription drug abuse 

• Resources available to you 

Questions Questions you you will will be be able able to to answer answer 

• What is the likelihood that one of you will develop 

chemical dependency in your lifetime? 

• What is the primary drug of choice for pharmacists? 

• What is the best referral you can make to a 

colleague ll iin ttrouble bl ? 

• What differentiates pharmacists from other 

addicted health professionals ? 

• What is the most common way people get 

controlled drugs without a prescription ? 

8/29/2012 

1

Some Some Facts Facts of of Interest Interest 

• One in every 8 Americans will have a problem with alcohol or another drug at 

some point in their lives. 

• Approximately 27 million Americans use illicit drugs regularly or are heavy 

drinkers. 

• An untreated alcoholics medical costs are 300% higher than a non alcoholic. 

• Interestingly, nicotine kills more Americans than alcohol, cocaine, heroin, 

methamphetamine, motor vehicle accidents, homicides, suicides, and fires 

combined. 

• Addiction is potentially the most serious health problem facing America in 2012. 

• The drug of choice for pharmacists is hydrocodone = other health professionals = 

alcohol 

• The most serious illness to afflict pharmacists in the 1st 15 years of practice is 

addiction. 

* 1) SAMHSA – Substance Abuse and Mental Health Services Administration 2012 statistics 

Addiction Addiction 101 101 

Experiential Learning 

Experience 

Addiction Addiction defined defined 

Addiction is defined as a chronic, relapsing, brain 

disease that is characterized by compulsive drug 

seeking and use despite harmful consequences 

Nora D. Volkow, MD 

Director : National Institute 

of Drug Abuse 

8/29/2012 

2

The Reward Center 

In time, serious and prolonged cocaine use can actually 

change the structure of the brain 

Causes shriveling of the axon filament and severe shortening of the 

dendrites leading to decreased conductivity of the dopamine neurons and 

eventually to anhedonia (the inability to feel pleasure or simply to feel OK) 

What it looks like in a real person 

8/29/2012 

3

Addiction In Pharmacy 

Environmental influences on pharmacists 

that increase vulnerability to addiction 

• Job stress ‐‐ 

– 400 opportunities to make a mistake – 

longer hours ‐‐ less help 

• Life’s usual stressors 

– PProblems bl with ith parents t or children, hild 

financial problems 

• Culture of tolerance 

‐‐ The tendency to self medicate 

+ feelings of invincibility 

• Exposure / access to 

addicting drugs “depression4” nida image 56230(1) 

It’s a setup for addiction 

GENETIC 

PREDISPOSI 

TION 

JOB STRESS 

DRUG 

ACCESS 

LIFE STRESS 

SELF SELF‐ 

MEDICATIN 

G 

TENDENCIES 

8/29/2012 

4

So what makes addicted pharmacists 

different from other health professionals? 

• The highest risk work setting period. 

• More paranoia regarding the loss of their license. 

• Fear of losing their job. 

• Greater issues with shame. 

• Miscellaneous differences: 

– Pharmacists rarely use IV drugs 

– Pharmacists rarely use illegal drugs 

– Pharmacists rarely obtain drugs from anywhere but their work setting 

– Most common drug of choice is hydrocodone 

• Best difference = pharmacists have the best success rate 

What to look for in a colleague 

• Increased absences 

• Late to work 

• Long bathroom breaks 

• mysterious disappearances 

• Appears groggy in the morning 

• Generally seems “different” 

• Stays late for no apparent reason 

• Confused easily 

• Increased problems in the rest of his/her life 

• Appears more unkempt than previously 

• Looks /sounds mildly impaired for short periods 

• Appears distant / hard to reach emotionally 

• Comes to work on days off and “helps out” for a short period 

• Finally –just seems very different than the way you knew him/her 

Best choice for help 

Illinois Professionals 

Health Program 

701 Lee Street 

Desplaines, Illinois 60015 

847 795 2810 

Helpline – 24 hours 

800 215 4357 

8/29/2012 

5

Illinois Illinois Professionals 

Professionals 

Health Health Program Program 

• Voluntary Program ‐‐ completely confidential 

• Pharmacy Board mandated program 

Resources for addicted health 

professionals : 

• Most states have Assistance Programs for each 

profession : Pharmacy – Medicine – Nursing - Dentistry 

• Pharmacists most often have a PRN or Pharmacists Recovery 

Network Program in their state. 

www.usaprn.com 

• Treatment facilities that specialize in treating health professionals: 

– Talbott Recovery Campus – Atlanta 

– Resurrection Behavioral Health – Chicago 

– Hazeldon – Minnesota 

– Betty Ford – California 

– Pine Grove – Mississippi 

– Professional Renewal Center – Kansas 

– Farley Center – Virginia 

– Rogers Memorial - Wisconsin 

What What you you can can do do to to help help 

your your patients patients 

‐ Have “help for addiction” pamphlets available (free = NIDA) 

‐ Have AA pamphlets available (inexpensive = www.aa.org) 

‐ Give direction on how to get to AA/NA and what they can expect. 

‐ Give options re where they can get a chemical dependency assessment 

(usually free) to find out if they really have a problem with drugs / alcohol 

‐ Post a sign offering confidential information regarding problems 

with alcohol / drugs 

‐ Inform physicians in your area that you have information about 

treatment and AA 

8/29/2012 

6

How to find a treatment center 

Online: 

www.Drug‐Rehab.org/Rehab_Center 

By Phone: 

877‐392‐5926 

Treatment Centers that offer free 

assessments 

Hospitals 

– Central Du Page Hospital –Winfield 

– Mercy Hospital –Chicago 

– Allexian Brothers Hospital –Schaumberg 

– Hinsdale Hospital –Hinsdale 

– Good Samaritan Hospital –Downers Grove 

– Lutheran General Hospital –Des Plaines 

– St St. Joseph Hospital – Lincoln Park 

– Holy Family Hospital – 

Treatment Centers 

Haymarket Center –Chicago 

Gateway Foundation –Chicago nida image “therapy” (1) 

Resurrection Behavioral Health –Downers Grove, Palos 

Share – Addison 

Lutheran Social Services –Chicago 

New Day Center ‐ Hinsdale 

12 12 Step Step Programs 

Programs 

Alcoholics 

Anonymous 

y 

WWW.CHICAGOAA.ORG 

8/29/2012 

7

Prescription Drug Abuse 

SAMHSA image 

Substance Abuse and Mental Health Services Administration 

[SAMHSA 

Reported Non‐Medical Prescription Drugs of Abuse 

(2005) 

Sedatives 

Tranquilizers 

Stimulants 

Painkillers 

4,700,000 

1,800,000 

1,100,000 

272,000 

Which is the most frequent way drugs are 

diverted for non‐medical use? 

1. Theft 

2. Drug Dealers 

3. Family members or friends 

4. Physicians 

5. Internet 

8/29/2012 

8

Internet Drug Abuse 

Study conducted in January 2004 identified 

157 internet sites that sold RXs 

� 90% did not require prescription 

� 41% “you do not need a Rx” 

� 49% offered online “consultation” 

� 4% required faxed Rx 

� 2% required mailed Rx 

� 4% no mention of Rx 

National Center on Addiction and Substance Abuse at Columbia University 2004 

157 Internet sites 

• None of the sites had safeguards blocking purchases 

by children 

• 144 offered schedule ll –V controlled drugs 

• 103 offered fentanyl, oxycontin, and hydrocodone 

• 47 % were outside the U.S. 

The web sites spring up and disappear quicklyNational 

Center on Addiction and Substance Abuse at Columbia University 2004 

Post lecture questions 

1. What are the odds one of you will suffer from an addiction at some point in your life? 

a. One in eight 

b. One in twenty 

c. Probably no one will 

d. One in fifty 

2. What is the most common drug of choice for pharmacists? 

a. Alcohol 

b. Hydrocodone 

c. Cocaine 

d. Marijuana 

3. What is the best referral you can make to a health professional in trouble? 

a. A treatment center 

b. Alcoholics Anonymous 

c. Illinois Professionals Health Program 

d. Department of Financial and Professional Regulation 

8/29/2012 

9

Post lecture questions 

4. The most frequent way drugs are diverted for non‐medical purposes is: 

a. Theft 

b. Drug dealers 

c. Family members or friends 

d. Physicians 

e. Internet 

5. What differentiates pharmacists from other addicted health professionals? 

a. Their primary drug of choice is alcohol. 

b. They work in a less stressful environment. 

c. They tend to use IV opioids more often. 

d. They tend to be more successful in recovery. 

The End 

Addiction Information Resources 

1. National Institute of Alcohol Abuse and Alcoholism N I A A A 

2. National Institute of Drug Abuse N I D A 

3. Substance Abuse and Mental Health Services Administration S A M H S A 

4. Addiction Science Research and Education Center–Univ.Of Texas College of Pharmacy 

5. Alcohol Research and Health – 10 th Special Report to Congress – NIAAA 

6. American Society of Addiction Medicine (ASAM) www.asam.org 

7. Center for Alcohol Studies - www.alcohol studies.rutgers.edu 

8. Guide to Mutual Support Resources – 

www.facesandvoicesofrecovery.org/resources/support/_home.php 

8/29/2012 

10

NIAAA = best resource for alcohol dependence 

Alcohol Alert –Neuroscience : Pathways to alcohol dependence 

http//:pubs.niaaa.nih.gov/publications/AA77/AA77.htm 

Who is at Risk for Alcoholism 

http://pubs.niaaa.nih.gov/publications/arh40/64‐75.htm 

Neurobiology of alcohol dependence 

http://pubs.niaaa.nih.gov/publications/313/185‐195.htm 

Alcohol Alert – Epidemiology –How Common is Alcohol and Other Drug 

Addiction? 

http://pubs.niaaa.nih.gov/publications/AA76/AA76.htm 

What is Addiction? 

http://pubs.niaaa.nih.gov/publications/arh312/93‐95.htm 

Helping Patients Who Drink too Much –A Clinicians Guide 

www.niaaa.nih.gov/guide 

Medication Management Support for Alcohol Dependence‐ Template 


Medications For Treating Alcohol Dependence 


8/29/2012 

11

Decisions, Decisions…Debates in Therapeutics 

Injectable Acetaminophen: 

What is its role in postoperative 

pain p management? g 

Daniel T. Abazia, Pharm.D., BCPS 

Pharmacy Clinical Coordinator 

Palos Community Hospital 


By the end of this knowledge‐based educational activity, 

participants should be able to: 

1. Explain the clinical and economic consequences of inadequate 

control of postoperative p p pain. p 

2. Identify elements of multimodal postoperative analgesia. 

3. Discuss clinical data for using injectable acetaminophen for 

management of postoperative pain. 

4. Describe the practical aspects of utilizing injectable 

acetaminophen within the acute care setting. 

Impact of Postoperative Pain 

Negative CLINICAL Outcomes: 

• Cognitive dysfunction 

• Coronary ischemia / myocardial infarction 

• Deep vein thrombosis / pulmonary embolism 

• Insomnia 

• Pneumonia 

• Poor wound healing and recovery 

Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results of from a national survey suggest 

postoperative pain continues to be undermanaged. Anesth Analg. 2003; 97:534‐40. 

Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth. 2001;87:62‐72. 

Disclosures 

The speaker has no actual or potential conflict of 

in relation to this presentation. 

Palos Community Hospital 

• Located in southwest 

suburbs of Chicago, IL 

• Community, non‐teaching 

• 436 licensed beds 

• Pharmacy satellite in OR 

2011 surgical statistics 

‐ Inpatient procedures: 3,993 

‐ Outpatient procedures: 4,575 

Postop Pain: Link to Chronic Pain 

• Retrospective analysis 

• Evaluated patients undergoing thoracotomy who developed 

chronic pain (n = 78) vs. those who did not (n = 71) one week 

postop 

• Pti Patients t who h ddeveloped l dchronic h i pain i hdi had increased... d 

� ↑ incidence of acute pain (p = 0.002) 

� ↑ severity of acute pain (p = 0.0001) 

� ↑ total �me having pain (p = 0.02) 

• Progression to chronic pain increased with intensity of acute 

postoperative pain 

Pluijms WA, Steegers MA, Verhagen AF, et al. Chronic post-thoracotomy pain: a retrospective 

study. Acta Anaesthesiol Scand. 2006; 50:804-8. 

8/29/2012 

1

Impact of Postoperative Pain 

• Pilot prospective cohort study 

• Purpose was to describe postoperative pain and health‐related QOL, and functioning 

1 month after hospital discharge 

• Participants underwent radical prostatectomy (RP), total hip replacement (THR), or 

total knee replacement (TKR), and completed the SF‐36 and questions from the 

Treatment Outcomes of Pain Survey (TOPS) 4 weeks after leaving the hospital 

– N = 30 ( RP = 15, TKR = 8, THR = 7) ) 

• Postoperative pain interfered with patient's ability to participate in desired activities 

(42.9% RP, 28.6% THR, 100% TKR), ability to sleep (21.4% RP, 71.4% THR, 75% TKR), 

and sexual functioning (50% RP, 28.6% THR, 25% TKR). During the first month after 

surgery, postop pain contributed to diminished health‐related QOL and interfered 

with activities important to patients. Mean SF‐36 scale scores in each surgical group 

were lower than US norms for physical functioning, physical roles, bodily pain, 

vitality and social functioning 

Strassels SA, McNicol E, Wagner AK, et al. Persistent postoperative pain, health‐related quality of life, and functioning 1 

month after hospital discharge. Acute Pain. 2004; 6(3):95‐104. 

Opioid Adverse Events 

• Historically, opioid monotherapy primary treatment of 

postoperative pain 

• 24 –48 hours postoperatively: morphine or hydromorphone 

PCA followed by oral hydrocodone, morphine, or oxycodone 

• In a systematic review of several randomized controlled trials 

analyzing opioid‐associated ADEs in postop patients, more than 

30% of patients reported GI ADEs 

– Most common: vomiting, constipation, and ileus 

– Most severe ADEs reported: sedation and resp depression 

Oderda GM, Said Q, Evans RS, et al. Opioid‐related adverse drug events in surgical hospitalizations: impact 

on costs and length of stay. Ann Pharmacother. 2007;41(3):400‐406. 

Wheeler M, Oderda GM, Ashburn MA, el al. Adverse events associated with postoperative opioid analgesia: 

a systemic review. J Pain. 2002;3(3):159‐180. 

Multimodal Analgesia 

Kehlet H, Dahl JB. Anesth Analg. 1993;77:1048‐1056. 

Active Learning Assessment 

POLL 

1. How many of you have had an inpatient or outpatient 

surgical procedure in your lifetime? 

2. How many of you have experienced pain following the 

procedure? 

3. How many of you have experienced one of the negative 

clinical outcomes following the procedure? 

4. How many of you have missed work or school following the 

procedure? 


• Use of different classes of analgesics that employ different 

pathways AND receptors to provide pain relief 

• Ideal components of multimodal analgesia include: 

‐ Agents with ability to modulate ≥ mechanism of pain transmission 

‐ Agents with an acceptable safety profile 

‐ Availability of an analgesic in a non‐oral formulation 

• Multimodal analgesia includes the use of local and systemic 

pharmaceutical agents in addition to perineural blockade and 

regional anesthesia 

White PF. Multimodal analgesia: its role in preventing postoperative pain. Curr Opin Investig Drugs. 2008; 

9(1):76‐82. 

Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin North Am. 

2005;23(1):185‐202. 

WHO Pain Ladder 

Adapted from World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO 

Expert Committee. Geneva: World Health Organization; 1990. 

8/29/2012 

2


American Society of Anesthesiologists – 2012 Practice Guideline: 

“The consultants and ASA members strongly agree that whenever possible, 

anesthesiologists should use multimodal pain management therapy. The 

ASA members agree and the consultants strongly agree that APAP should 

be considered as part of a postoperative multimodal pain management 

regimen; i both b hthe h consultants l and d ASA members b agree that h COX‐2 

inhibitors, nonselective NSAIDs, and calcium channel ‐2‐ antagonists 

(gabapentin and pregabalin) should be considered as part of a 

postoperative multimodal pain management regimen. Moreover, the 

ASA members agree and the consultants strongly agree that, unless 

contraindicated, patients should receive an around‐the‐clock regimen of 

NSAIDs, COX‐2 inhibitors, or APAP.” 

American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute 

pain management in the perioperative setting: an updated report by the American Society of 

Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2012; 116:248–73. 

• Oral formulation available 

in US since 1955 

• IV formulation approved by 

FDA in November 2010 for 

use in (pain (pain, fever) 

Acetaminophen 

• Recognized as safe and 

effective at recommended 

doses Adapted from: 

http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInf 

o.cfm?archiveid=5836 

Care needed with IV acetaminophen. Am J Health‐Syst Pharm. 2011; 68:1775‐6. 

Absorption 

Peak concentration is observed at the 

end of infusion 

Distribution 

Mean Vd reported in several studies has 

ranged d ffrom 69.2 ‐ 85 L; not extensively l 

plasma protein–bound (10% to 25%) 

Elimination 

Half‐life is 2.4 hours in adults, 2.9 hrs 

in adolescents, 1.5 to 3 hrs in children, 

4.2 hrs in infants 

Pharmacokinetics 

Adapted from: http://www.fda.gov/ohrms/dockets/ac/02/b 

riefing/3882B1_13_McNeil‐Acetaminophen.htm 

Ofirmev injection prescribing information. San Diego, CA: Cadence Pharmaceuticals, Inc.; Nov 2010. Available 

at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c5177abd‐9465‐40d8‐861d‐3904496d82b7. 

Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen). Drugs 2009; 69 (1): 101‐113. 


Jeopardy 

A concept that utilizes multiple classes of medications with 

acceptable safety profiles that employ different pathways 

and receptors to provide relief of pain. 

What is multimodal analgesia? 

Pharmacodynamics 

• Analgesic effect of APAP involves both central and peripheral 

actions 

‐ Inhibition of nitric oxide synthesis pathway 

‐ Inhibition of prostaglandin synthesis 

• Analgesic effects of paracetamol may also involve the 

serotonergic system 

‐ Pickering and colleagues identified agonists of the serotonin 5‐HT3 

receptor, granisetron and tropisetron, completely blocked the 

analgesic effect of paracetamol in healthy males 

Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen). Drugs. 2009; 69 (1): 101‐113. 

Pickering G, Loriot MA, Libert F, et al. Analgesic effect of acetaminophen in humans: first evidence of a central 

serotonergic mechanism. Clin Pharmacol Ther. 2006 Apr; 79 (4): 371‐8 

Dosage and 


Dosage and Administration 

IV APAP Oral APAP Rectal APAP 

50 kg: 1 gm q6h or 

650 mg q4h 

(Max 4 gm/day) 

< 50 kg or ages 2–12: 

Adults: 650 mg or 1 

gm q4–6h or 1.3 gm 

ER tablets q8h PRN 

(Max 4 gm/day) 

Children Children aged < 12: 

15 mg/kg q6h or 12.5 

weight‐adjusted 

mg/kg q4h (Max 75 

40–480 mg q4–6 h 

mg/kg/day) 

(Max 5 doses/day) 

15 min infusion 

Formulation 1 gm/100 mL SDV Tablet, capsule, 

suspension, solution 

Adults: 325–650 mg 

q4h PRN 

Children aged 2–12: 

weight‐adjusted dose 

160–480 mg q4h 

(Max 5 doses/day) 

Children aged < 2: 

individualized 

Suppository 

Ofirmev injection prescribing information. San Diego, CA: Cadence Pharmaceuticals, Inc.; Nov 2010. Available 

at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c5177abd‐9465‐40d8‐861d‐3904496d82b7. 

Yeh YC, Reddy P. Clinical and economic evidence for intravenous acetaminophen. Pharmacother. 2012; ; 

32(6):559‐79. 

8/29/2012 

3

Safety Profile 

• Amar et al confirmed that doses > 4 grams per day may cause 

centrilobular hepatic necrosis in adults 

‐ Administration of scheduled doses for more than a few days 

requires caution 

• Singla et al compared the safety profile of IV APAP (1 gm q6h 

and 650 mg q4h) with the standard‐of‐care in 213 patients. 

‐ A lower proportion (~15% vs. 26.7) of patients with elevated 

LFTs in the IV APAP groups compared with the control group 

Amar PJ, Schiff ER. Acetaminophen safety and hepatotoxicity—where do we go fromhere? Expert Opin Drug 

Saf. 2007;6(4):341‐355. 

Singla N, Ferber L, Bergese S, et al. A phase III, multi‐center, open‐label, prospective, repeated dose, 

randomized, controlled, multi‐day study of the safety of intravenous acetaminophen in adult inpatients. 

Proceedings and Abstracts of the 34th Annual American Society of Regional Anesthesia Meeting and 

Workshops. April 30 to May 3, 2009; Phoenix, AZ. Poster 96. 


LA is a 92 year old male with a PMH significant for colon polyps, 

gastric ulcers, hypertension, hyperlipidemia, atrial fibrillation – 

s/p pacemaker recently diagnosed with early stage colon CA. He 

is admitted for a partial colectomy and your medical team asks 

you what h the h BEST S postoperative i analgesic l i regimen i would ld bbe 

for this patient. He is allergic to morphine (itching). 

HINT: Your formulary analgesics include IV and PO APAP, 

celecoxib, fentanyl IV and TD, hydrocodone, hydromorphone, 

PO ibuprofen, ketorolac, morphine, and oxycodone. 

IV Acetaminophen DUE 

Inclusion Exclusion 

≥18 year of age 

General surgical procedures 

Inpatient at least 24 hours post –op 

Received min 2 doses of 1gm IV APAP 

Body weight 50‐120 kg 

Numeric pain scale used (1‐10) 

ASA class 1‐3 

Primary endpoint 

Allergy or hypersensitivity to APAP 

Transaminases > 2 x ULN) 

SCr > 2 mg/dL 

Uncontrolled chronic disease 

History of alcohol or drug abuse 

Pregnant or breastfeeding 

Treatment of fever 

Total morphine and NSAID equivalent dose during first 24 hours 

Secondary endpoints 

PACU LOS and pain score reduction 

Meta ‐ Analyses 

• Rømsing et al 1 evaluated the analgesic effect of rectal, IV, and oral 

formulations of APAP was evaluated (24 studies, 2023 patients) 

‐ APAP, given either rectally or IV, was effective for post‐op pain relief 

‐ Addition of NSAIDs to APAP predictably improved pain relief, whereas 

adding APAP to NSAIDs was less predictable 

Remy et al2 and Elia et al3 • Remy et al evaluated outcomes of APAP (IV PO and 

2 and Elia et al3 evaluated outcomes of APAP (IV, PO, and 

PR) in combination with PCA after orthopedic and abdominal surgery 

‐ 7 trials (491 patients) and 10 trials (769 patients), respectively 

‐ Compared with placebo, APAP given post‐op significantly reduced 

morphine requirements by ~20% (8‐10 mg) on post‐op Day 1 

‐ Not associated with a significant reduction in post‐op N/V, sedation, 

urinary retention, and respiratory depression 


• Randomized, retrospective, case‐control evaluation 

• Evaluated post‐op pain management 3 months before and 3 

months after IV APAP added to PCH formulary 

• 25 patients in each group 

• Objective was to investigate if the use of IV APAP reduces the 

use of opioids and NSAIDs in post‐op general surgical patients 


Results 

•↓ total opioid use by 24% 

•↓ total NSAID use by 100 % 

•↓ their total pain score by 9% 

•Did NOT reduce their PACU 

length of stay 

Limitations 

•Retrospective, observational study 

•IV APAP was not available in OR 

•Not all patients received IV APAP 

as a scheduled med 

•IV APAP group received higher 

doses of total fentanyl, midazolam, 

dexamethasone and ketorolac 

8/29/2012 

4

Prescribing 

Impact on Med‐Use Process 

• Which dose...650 mg or 1000 mg (adults)? 

• Dose calculation required for pediatrics 

• Scheduled vs. PRN 

• Restrictions to specialists, units, or patient types? 

Dispensing 

• Doses < 1000 mg require manipulation 

• Contents of vial must be administered within 6 hrs 

• Adequate space in automated dispensing machine (ADM)? 

Monitoring 


• Ensure use of < 4 grams per day of APAP 

‐ Hold use of combo APAP products 24 to 48 hours post‐op 

> FDA requiring manufacturers to limit APAP in prescription 

products to 325 mg per single dosage unit and add a black‐ 

box warning by 2014 

• Cost‐effectiveness 

‐ IV to PO conversion 

‐ Automatic stop dates/times, e.g. 24 hours after 1st dose 

Food and Drug Administration. Prescription drug products containing acetaminophen; actions to reduce 

liver injury from unintentional overdose. Fed Regist. 2011; 76:2691‐7. 

Conclusions 

• IV APAP is generally well tolerated at recommended doses 

• Clinical trials indicate IV APAP is an effective analgesic in a 

variety of inpatient and outpatient surgical procedures 

• Use should be limited to ≤ 24 hours postoperatively and 

patients who can not tolerate PO or PR administration 

• Institution‐specific strategies are required to ensure safe use of 

IV APAP 



• Infusion pump required 

‐Errors related to infusion pump programming have been reported 

to the Institute for Safe Medication Practices (ISMP) 

> ISMP recommends use of both mg and mL dosing when 

prescribing and communicating dose information 

• Y‐site compatibility for patients with multiple infusions 

Institute for Safe Medication Practices (ISMP).IV acetaminophen and overdoses in kids. ISMP Medication 

Safety Alert. Apr 2012; 17(8):1,4. 


Which of the following are issues that must be addressed when 

evaluating IV APAP for formulary addition? 

I. Ensuring patients do not receive > 4 gm APAP per 24 hrs 

II. Manipulation of vials when doses are less than 1 gm 

III. Risk of infusion pump p perrors if doses not ordered in mg g and 

mL 

a. I only 

b. III only 

c. I and II 

d. II and III 

e. I, II, and III 

Thank you! 

dabazia@paloscomm.org 

8/29/2012 

5

References 

1. Rømsing J, Møiniche S, Dahl JB. Rectal and parenteral paracetamol, and paracetamol in combination with 

NSAIDs, for postoperative analgesia. Br J Anaesth. 2002;88:215–26. 

2. Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side‐effects and consumption after major 

surgery: a meta‐analysis of randomized controlled trials. Br J Anaesth. 2005;94:505–13. 

3. Elia N, Lysakowski C, Tramer M. Does multimodal analgesia with acetaminophen, nonsteroidal 

antiinflammatory drugs, or selective cyclooxygenase‐2 inhibitors and patient‐controlled analgesia morphine 

offer advantages over morphine alone? Anesthesiology. 2005;103:1296–304. 

8/29/2012 

6

2012 ICHP Annual Meeting 

Injectable Acetaminophen: What is its role in postoperative pain management? 

Bibliography 

1. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results of from a 

national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 

2003; 97:534-40. 

2. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth. 

2001; 87:62-72. 

3. Pluijms WA, Steegers MA, Verhagen AF, et al. Chronic post-thoracotomy pain: a 

retrospective study. Acta Anaesthesiol Scand. 2006; 50:804-8. 

4. Strassels SA, McNicol E, Wagner AK, et al. Persistent postoperative pain, health-related 

quality of life, and functioning 1 month after hospital discharge. Acute Pain. 2004; 6(3):95- 

104. 

5. Oderda GM, Said Q, Evans RS, et al. Opioid-related adverse drug events in surgical 

hospitalizations: impact on costs and length of stay. Ann Pharmacother. 2007;41(3):400-406. 

6. Wheeler M, Oderda GM, Ashburn MA, el al. Adverse events associated with postoperative 

opioid analgesia: a systemic review. J Pain. 2002;3(3):159-180. 

7. White PF. Multimodal analgesia: its role in preventing postoperative pain. Curr Opin 

Investig Drugs. 2008; 9(1):76-82. 

8. Joshi GP. Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin 

North Am. 2005;23(1):185-202. 

9. Kehlet H, Dahl JB. The value of multimodal or balanced analgesia in the postoperative pain 

treatment. Anesth Analg. 1993;77:1048-1056. 

10. World Health Organization. Cancer Pain Relief and Palliative Care, Report of a WHO Expert 

Committee. Geneva: World Health Organization; 1990. 

11. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice 

guidelines for acute pain management in the perioperative setting: an updated report by the 

American Society of Anesthesiologists Task Force on Acute Pain Management. 

Anesthesiology 2012; 116:248–73. 

12. Care needed with IV acetaminophen. Am J Health-Syst Pharm. 2011; 68:1775-6. 

13. Duggan ST, Scott LJ. Intravenous paracetamol (acetaminophen). Drugs. 2009; 69 (1): 101- 

113. 

14. Pickering G, Loriot MA, Libert F, et al. Analgesic effect of acetaminophen in humans: first 

evidence of a central serotonergic mechanism. Clin Pharmacol Ther. 2006 Apr; 79 (4): 371-8 

15. Ofirmev injection prescribing information. San Diego, CA: Cadence Pharmaceuticals, Inc.; 

Nov 2010. Available at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=c5177abd- 

9465-40d8-861d-3904496d82b7. 

16. Yeh YC, Reddy P. Clinical and economic evidence for intravenous acetaminophen. 

Pharmacother. 2012; 32(6):559-79. 

17. Amar PJ, Schiff ER. Acetaminophen safety and hepatotoxicity—where do we go fromhere? 

Expert Opin Drug Saf. 2007;6(4):341-355. 

18. Singla N, Ferber L, Bergese S, et al. A phase III, multi-center, open-label, prospective, 

repeated dose, randomized, controlled, multi-day study of the safety of intravenous 

acetaminophen in adult inpatients. Proceedings and Abstracts of the 34th Annual American

Society of Regional Anesthesia Meeting and Workshops. April 30 to May 3, 2009; Phoenix, 

AZ. Poster 96. 

19. Rømsing J, Møiniche S, Dahl JB. Rectal and parenteral paracetamol, and paracetamol in 

combination with NSAIDs, for postoperative analgesia. Br J Anaesth. 2002;88:215–26. 

20. Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects and 

consumption after major surgery: a meta-analysis of randomized controlled trials. Br J 

Anaesth. 2005;94:505–13. 

21. Elia N, Lysakowski C, Tramer M. Does multimodal analgesia with acetaminophen, 

nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patientcontrolled 

analgesia morphine offer advantages over morphine alone? Anesthesiology. 

2005;103:1296–304. 

22. Institute for Safe Medication Practices (ISMP).IV acetaminophen and overdoses in kids. 

ISMP Medication Safety Alert. Apr 2012; 17(8):1,4. 

23. Food and Drug Administration. Prescription drug products containing acetaminophen; 

actions to reduce liver injury from unintentional overdose. Fed Regist. 2011; 76:2691-7.


INTRAVENOUS ACETAMINOPHEN 

A DRUG UTILIZATION EVALUATION 

Jamie Brockhouse 

St John’s Hospital 

Springfield, Il 

Learning Objective 

• Upon completion of this program, pharmacists 

should be able to: 

– Describe the role in therapy for IV acetaminophen 

Additional Goal: 

– Compare the advantages and disadvantages for IV 

acetaminophen 

Post Surgical Pain Management: 

Our Current Approach 

• Surgical pain mechanism 

– Inflammation as a result of tissue trauma 

– Direct nerve damage 

• Multimodal analgesia 

– Involvement of several different disciplines 

– Goal: maximize pain relief, minimizing side effects and 

contain cost 

• Most commonly used pharmacologic agents 

– Opioids 

– NSAIDs 


The speaker has no actual or 

potential conflict of interest in 

relation to this activity 

Question 

• Does your organization restrict the use of IV 

Acetaminophen? 

Advantages and Disadvantages to 

Current Approach 

• Advantages 

– Dosing flexibility 

– Multiple routes of administration 

– Low cost 

• Disadvantages 

isadvantages 

– Nausea and vomiting 

– Slowing of GI transit 

• Constipation/post op ileus 

– Depression of brainstem control of respiratory drive 

– Histamine release 

• itching 

8/29/2012 

1

A New Approach 

IV Acetaminophen 

• Proposed Benefits 

– Decreased utilization of morphine equivalents 

• Less opioid‐related adverse effects 

– Earlier mobilization 

• Increased physical therapy participation 

• Decreased risk of DVT 

– Decreased length of stay 

• Reduction of hospital cost 

– Increased patient satisfaction 

A New Approach 

IV Acetaminophen 

• Disadvantages 

– Kinetics 

• Tmax: more predictable than other routes of acetaminophen 

• Analgesic effect of multiple routes similar 

• Analgesic effect of rectal formulation prolonged 

– Patient selection 

• Contraindicated with severe liver impairment or acute liver disease 

• Use with caution: 

– Alcoholism, malnutrition, hepatic impairment, renal impairment 

(CrCl

IV Acetaminophen –Average Length of 

Stay and Charges 

May 2012, ICD‐9 Code 715.36 

(When IV APAP was used) 

May 2011, ICD‐9 Code 

715.36(When IV APAP was NOT 

used) 


715.35(When IV APAP was used) 


715.35(When IV APAP was NOT 

used) 

May 2012, ICD‐9 Code 654.21 

(When IV APAP was used) 

May 2011, ICD‐9 Code 654.21 

(When IV APAP was NOT used) 

Average Length of Stay Average Charges 

2.68 days $36,100 

2.88 days $35,600 

2.56 days $42,600 

3 days $42,500 

2.56 days $7,700 

2.4 days $7,600 

Review 

• What positives do you see from IV 

Acetaminophen use? 

• What negatives do you see from IV 

Acetaminophen use? 

• What additional research data would you like 

to see about IV Acetaminophen use? 


Which of the following statements is/are true regarding 

the infusion of intravenous acetaminophen? 

A. Infusion time is 30 minutes 

B. Cmax occurs at 30 minutes 

C. Overall AUC is similar to oral administration 

D. After penetration of the seal the product should be 

used within 12 hour 


IV Acetaminophen – Multiple 

Dosing 

• 15 patients who 

received multiple 

doses of IV APAP 

(average of 3.23 

doses) were randomly 

selected and 

compared to 15 

patients who received 

a single dose of IV 

APAP. 

Total oral 

morphine 

equivalent 

dose 

Multiple 

doses of IV 

APAP 

Single dose 

of IV APAP 

Calculated 

p-value 

27.93mg 26.47mg 0.8946 

Symptoms of 6 patients, 5 patients, 1.0 (Fisher’s 

nausea/vomiti receiving g total receiving g total exact test) ) 

ng 0-24 hours of 10 doses of of 8 doses of 

after surgery ondansetron ondansetron 

4mg 

4mg 

Average 

lowest oxygen 

saturation 0- 

24 hours after 

surgery 

Average 

lowest 

respiratory 

rate 0-24 

hours after 

surgery 

Conclusion 

94.2% 94.83% 

16.2 16.08 

• Place in therapy is undetermined 

– Results of our DUE failed to demonstrate that clinical 

advantages outweigh the economic burden 

• Additional research needed 

– Larger sample size 

– Time to first physical therapy 

– Frequency of nausea and vomiting 

• Needs to be proven fiscally responsible 

– Anticipated benefits must be observed 

Questions 

8/29/2012 

3

References 

• Schechter, Leslie N., BS,PharmD. "Multimodal Approach to Pain 

Management Focus on Ofirmev (acetaminophen) Injection." U.S. 

Pharmacist (2012): 1‐12. Apr. 2012. Web. 

• Yeh, Yu‐Chen, M.S., and Prabashni Reddy, Pharm.D.,M.Med.Sc. "Clinical 

and Economic Evidence for Intravenous Acetaminophen." 

Pharmacotherapy 32.6 (2012): 559‐79. Web. 

• KKodali, d li Bhavani‐Shankar, Bh i Sh k MD, MD and d Jasmeet J tOb Oberoi, i MD. MD "REFERENCES "REFERENCES." " 

Management of Postoperative Pain. UpToDate, 10 Oct. 2011. Web. 12 Aug. 

2012. . 

• Zacharoff, Kevin, MD. "The Role of Rational Polypharmacy in Pain 

Management." PainEDU.org { Articles }. N.p., 11 Mar. 2008. Web. 12 Aug. 

2012. . 

8/29/2012 

4


Bupivacaine liposomal injection 

Will it stick ti k around? d? 

Elizabeth Short, Pharm.D. 

PGY2 Critical Care 

Northwestern Memorial Hospital 


• Determine criteria necessary for formulary 

approval 

• Interpret clinical trial data and apply to 

formulary management 

• Efficacy 

• Safety 

Formulary Criteria 

• Avoid superfluous, expensive additions 

Conflicts 

• I have no conflicts of interest to declare 

Bupivacaine liposome injectable 

suspension (Exparel) 

Approved Indication: 

FFor administration d i i t ti iinto t th the surgical i lsite it tto 

produce postsurgical analgesia1 1. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=59067 

http://www.drugdevelopment‐technology.com/projects/6855/images/138835/large/1‐bottle.jpg 



• Pacira Pharmaceuticals, Inc. 

• FDA Approval: October, 2011 

• Intended to provide longer duration of effect 

8/29/2012 

1



Multivesicular Liposomes 

http://www.exparel.com/images/exparel_how_to_use.jpg 

Efficacy 

Primary efficacy endpoint: 

Pain intensity score summation over time 

Percentage of Patients Pain‐free vs Hours 

Golf, et al. Adv Ther. 2011;28:776-88 

Liposomal bupivacaine 120 mg 

Placebo 

FDA Approval 

Based on two clinical trials 

• Bunionectomy (Golf 2011) 

• Hemorrhoidectomy (Gorfine 2011) 


Gorfine et al. Dis Colon Rectum. 2011;54:1552-9. 

Efficacy 

Primary efficacy endpoint: 

Pain intensity score summation over time 

No benefit beyond 24 hours 

No Opioid Rescue Medications vs Hours 



Placebo 

8/29/2012 

2

Cumulative Pain Score through 72 Hours 

Cumulativ ve Pain Score 


P < 0.0001 

No Opioid Rescue Medications vs Hours 



Placebo 

FDA Review 

“Between 24 and 72 hours after study drug 

administration, there was minimal to no 

difference between EXPAREL and placebo 

treatments on mean pain intensity; however, 

there was an attendant decrease in opioid 

consumption, the clinical benefit of which was 

not demonstrated.” 

Mean Total Amount of Opioids Over 72 Hr 

Milligramss 

(mg) 


Marketing 

P < 0.006 

“One dose of Exparel provides up to 72 hours of 

postsurgical pain control with a decrease in 

opioid consumption without the need for 

catheters or pumps.” 

Safety 

• No primary safety outcome defined 

• Identified opioid‐ related adverse effects 

8/29/2012 

3

Error Potential 

• Inadvertent IV administration 

• Institute for Safe Medication Practices (ISMP) 

issued warning 

http://www.drugdevelopment-technology.com/projects/6855/images/138835/large/1-bottle.jpg 

http://wbma.images.worldnow.com/images/19134941_BG2.jpg 



Recommend to add to formulary 

aa. Yes 

b. NO 

http://www.drugdevelopment‐technology.com/projects/6855/images/138835/large/1‐bottle.jpg 

Unpublisheed 

Trials 

8 Unpublished Trials 

plain bupivacaine as active comparator 

3 

Liposomal bupivacaine 

better 

5 

No benefit over 

plain bupivacaine 


Bupivacaine liposomal injection 

Will it stick around? 

Elizabeth Short, Pharm.D. 

PGY2 Critical Care 

Northwestern Memorial Hospital 

8/29/2012 

4

Decisions, Decisions… Debates in Therapeutics 

Mupirocin 

Sheila Wang, Pharm.D., BCPS AQ-ID 

Assistant Professor Pharmacy Practice 

Midwestern University Chicago College of Pharmacy 


1. Recognize the recent rise in MRSA rates in hospital 

and community settings and its infectious impact on 

morbidity and mortality. 

2. Describe how Staph aureus carriers increase their risk 

of infection once entering hospital settings settings. 

3. Name the most common method of decolonization in 

the United States. 

4. Recall the three uses of mupirocin for decolonization 

discussed in this presentation. 

5. Indicate the most concerning consequence of wide 

spread mupriocin use. 

• In the U.S., MRSA rates range from 50-60% for non-ICU and ICU settings 

• More morbidity and mortality associated with MRSA versus MSSA infections 

- Mortality as high as 25% in some settings. 

Styers D, et al. Ann Clin Microbiol Antimicrob 2006 

Wyllie DH, et al. BMJ 2006 

Disclosure Statement 

• The speaker has no conflicts of interest or relationships 

with commercial entities that may be referenced in this 

presentation 

Boucher HW et al. CID 2009 

Rybak M, AJHP 2009 

Liu C, et al. CID 2011 

Staph aureus colonization 

• Common site is anterior nares 

– Carriers of Staph aureus in healthy adults (30%) 

– High rates of colonization in hospital inpatients, IVDU, insulindependent 

diabetics, HIV positive and hemodialysis patients 

– Extranasal colonization 

• Throat, perineum, GI tract, cutaneous sites 

• Prerequisite to staphylococcal infections 

– Two to 12 times higher vs. non-colonizers 

– Bloodstream, dialysis-associated and surgical site infections 

8/29/2012 

1

Decolonization Methods 

• Anti-septic body wash therapy 

– Chlorhexidine, Hexachlorophene, Bleach, Other 

• Topical and/or nasal therapy 

– Mupirocin, Bacitracin, Other 

• Oral antimicrobial therapy 

– Rifampin, TMP/SMX, Clindamycin, Minocycline 

Use of Mupirocin for Decolonization 

• Nasal Staphylococcal carriage prior to elective surgery 

• Inpatient MRSA colonization – Infection control programs 

• Recurrent skin and soft tissue infections – Communityy 

associated MRSA 

Evidence: Surgical Patients 

• Van Rijen M et al. 2008 

Van Rijen MML, JAC 2008 

Mupirocin 

• Formally known as pseudomonic acid A 

– Major metabolite derived from submerged fermentation by 

Pseudomonas fluorescens. 

• Bacterial RNA and protein synthesis inhibitor 

– Inhibits bacterial isoleucyl-transfer RNA (tRNA) synthetase 

• Bactericidal: topical administration after 24 to 36 hours of 

exposure 

• Highly active (in vitro) against staphylococcal strains 

(including MRSA) and streptococci (except enterococci) 

• Lacks (in vitro) activity against gram-negatives, 

anaerobes and fungi 

– Minimal activity against normal skin flora (Micrococcus, 

Corynebacterium and Propionibacterium spp.) 


• Kluytmans JA et al. 1996 

– Single-center, unblinded intervention trial 

– Perioperative decolonization with mupirocin nasal ointment 

reduces surgical-site infection rates (Staph aureus) in 

cardiothoracic di th i surgery 

– ITT analysis: Significant reduction in SSI rate 

• 7.3% (control) vs 2.8% (intervention); P < 0.0001 

– Limitation: historical controls 

Kluytmans JA, et al. Infect Control Hosp Epidemiol 1996 


• Van Rijen M et al. 2008 

• No effectiveness was observed among the non-carriers 

(RR 1.09, 95% CI 0.52–2.28). 

Van Rijen MML, JAC 2008 

8/29/2012 

2

Bode L et al. NEJM 2010 



Evidence: Inpatient ICU MRSA Colonization - 

Infection Control 

Fraser TG et al. Infect Control Hosp Epidemiol 2010. 





Departments included: internal medicine, cardiothoracic surgery, vascular surgery, orthopedics, 

gastrointestinal surgery, or general surgery 



Fraser TG et al. Infect Control Hosp Epidemiol 2010. 

8/29/2012 

3



• Forty-five US hospital currently participating in a cluster 

randomized trial 

• Prevention of MRSA infection in ICUs 

1. Positive screening cultures of ICU admission � contact precaution 

2. Positive screening cultures of ICU admission � decolonization 

3. Universal decolonization of ICU admission without screening 

Platt R et al. Med Care 2010 

Evidence: Recurrent Skin and Soft Tissue 

Infections – Community-associated MRSA 

• Recurrent SSTI despite optimizing wound care/hygiene measures 

• Ongoing transmission among household members or close 

contacts despite optimizing wound care/hygiene measures 

• Decolonization strategies should be offered in conjunction with 

ongoing reinforcement of hygiene measures 

• Mupirocin twice daily for 5-10 days 

• Mupirocin twice daily for 5-10 days and topical body decolonization regimens 

with a skin antiseptic solution (eg, chlorhexidine) for 5–14 days or bleach baths 

• Evidence: CIII 


Tenover FC. AAC 2012 

Mupirocin Resistance in the US 

Evidence: Recurrent Skin Soft Tissue 

Infections – Community-associate MRSA 


Mupirocin for Decolonization 

• Clinical and epidemiological outcomes influencing use 

– Perioperative eradication of S. aureus colonization 

– Controlling for HA-MRSA and transmission 

– Incidence of CA-MRSA 

• Learning from others 

– UK – screening includes all hospital admissions 

– Utilizing much more mupirocin 

– UK - high-level mupriocin resistance ~ 12% 

• MICs >/= 512 mg/mL 

• Independently associated with decolonization failure 

• Selection of increased drug resistance in S. aureus 

– Plasmid carrying resistance determinants to other antimicrobial agents, including 

macrolides, gentamicin, tetracycline, and trimethoprim 

References 

1. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice L, et al. Bad Bugs, No Drugs: No ESKAPE! An 

Update from the Infectious Diseases Society of America. Clinical Infectious Diseases 2009;48:1–12. 

2. Rybak M, Lomaestro B, Rotschafer JC, Moellering R.,Craig W,Billeter M, et al. Therapeutic monitoring of 

vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the 

Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst 

Pharm. 2009; 66:82-98. 

3. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, et al. Clinical Practice Guidelines by the 

Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus 

Infections in Adults and Children. Clinical Infectious Diseases 2011;1–38. 

4. Styers D, Sheehan DJ, Hogan P, Sahm DF. Laboratory-based surveillance of current antimicrobial resistance 

patterns and trends among Staphylococcus aureus: 2005 status in the United States. Ann Clin Microbiol 

Antimicrob 2006;5:2. 

5. Wyllie DH, Crook D, Peto T. Mortality after Staphylococcus aureus bacteraemia in two hospitals in Oxfordshire, 

1997-2003: cohort study. BMJ 2006; BMJ 2006;333:281. 

6. Kluytmans JA, Mouton JW, VandenBergh MF, Manders MJ, Maat AP, Wagenvoort JH, et al. Reduction of surgicalsite 

infections in cardiothoracic surgery by elimination of nasal carriage of Staphylococcus aureus. Infect Control 

Hosp Epidemiol. 1996 Dec;17(12):780-5. 

7. van Rijen M, Bonten M, Wenzel RP, Kluytmans J. Intranasal mupirocin for reduction of Staphylococcus aureus 

infections in surgical patients with nasal carriage: a systematic review. JAC 2008;61:254. 

8. Bode LGM, Kluytmans JAJW, Wertheim HFL, Bogaers B, Vandenbroucke-Grauls CM, Roosendaal R, et al. 

Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010; 362: 9–17. 

9. Fraser TG, Fatica, C, Scarpelli, M, Arroliga, AC, Guzman J, Shrestha,NK. Decrease in Staphylococcus aureus 

Colonization and Hospital- Acquired Infection in a Medical Intensive Care Unit after Institution of an Active 

Surveillance and Decolonization Program Infect Control Hosp Epidemiol 2010; 31(8):779-783. 

10. Platt R, Takvorian SU, Septimus E, Hickok J, Moody J, Perlin J, et al. Cluster Randomized Trials in Comparative 

Effectiveness Research: Randomizing Hospitals to Test Methods for Prevention of Healthcare-Associated. Med 

Care 2010;48: S52–S57. 

11. Tenover FC, Tickler IA, Goering RV, Kreiswirth BN, Mediavilla JR, Persing DH. Characterization of Nasal and 

Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals 

Antimicrob. Agents Chemother. 2012, 56(3):1324. 

8/29/2012 

4


Which of the following resistant gram‐positive 

organism has been on the rise in hospital and 

community settings resulting in mortality as 

high as 25%? 

A. Methicillin‐sensitive Staph aureus 

B. Methicillin‐resistant Staph aureus 

C. Vancomycin resistant enterococci 

D. Multidrug resistant Streptococcus pneumonia 


Which of the following methods of decolonization 

was found to be the most favorable among 

infectious diseases consultants? 

AA. Rifampin 

B. Bleach 

C. Chlorhexidine with Bacitracin 

D. Mupriocin with or without Chlorhexidine 


Widespread use of mupirocin will likely increase 

the risk of: 

A. Cost 

B Allergic reactions 

B. Allergic reactions 

C. Resistance 

D. Tolerance 


Risk of infection increases when asymptomatic 

carriers of Staph aureus enter this setting: 

A. Hospitals 

BB. Nursing home 

C. Rehabilitation centers 

D. Retirement centers 


Compelling evidence to support the use of 

mupirocin as a decontamination agent is largely 

available for: 

A. Nasal Staphylococcal carriage prior to elective 

surgery g y 

B. Inpatient MRSA colonization –Infection control 

programs 

C. Recurrent skin and soft tissue infections – 

Community‐associated MRSA 

D. Elderly long‐term care facility residents colonized 

with Staph aureus 

8/29/2012 

5

Residency Project Pearls 

Adherence to and Outcomes 

Associated with a Clostridium 

difficile Infection Guideline at a 

Large Teaching Institution 

Speaker has no conflicts of interest to disclose. 

RaeAnna C. Zatarski, Pharm.D. 


Advocate Lutheran General Hospital (ALGH) 

• Academic research 

institution 

• Level 1 trauma center 

• 645 bed capacity 

• Located in Park Ridge, 

Illinois 

Treatment 

• Early treatment of CDI 

– Metronidazole designated as first line agent 

– Vancomycin limited to failures or intolerance 

• Increased incidence of metronidazole failures caused 

shift in clinical practice 

• Zar trial (2007) 

– Mild‐moderate: metronidazole noninferior to vancomycin 

– Severe: vancomycin superior to metronidazole 

Jung KS, et al. Gut Liver. 2010 Sept;4(3):332‐7. 

Zar FA, et al. Clin Infect Dis. 2007 Aug 1;45(3):302‐7. 

Objectives 

• Select a treatment plan for a patient with Clostridium 

difficile infection based on the severity of illness. 

• Identify potential barriers to adherence to the 

Clostridium difficile infection treatment guidelines. 

Clostridium difficile Infection (CDI) 

� Causes 20 – 30% of antibiotic associated diarrhea 

• Risk factors for CDI 

– Prior antimicrobial or proton pump inhibitor use 

– Recent immunosuppressive therapy 

• Epidemiology 

– Incidence: 85,700 in 1993 → 301,200 in 2005 

– Mortality: 5.7 / million in 1999 → 23.7 / million in 2004 

– Incidence at ALGH: 400 patient cases annually 

Schroeder MS. Am Fam Physician. 2005 March 1;71(5):921‐8. 

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010 May;31(5):431‐55. 

Treatment 

• ALGH approved physician‐managed CDI treatment 

guidelines in July 2009 

– Stratified patients into severity categories according to 

clinical signs and symptoms 

– Recommended specific treatment regimens based on 

severity category 

• SHEA / IDSA published their revised CDI treatment 

guidelines in May 2010 

Cohen SH, et al. Infect Control Hosp Epidemiol. 2010 May;31(5):431‐55. 

8/29/2012 

1

ALGH Recommendations for Initial Treatment 

Clinical Severity Supportive Clinical Data Recommended Treatment 

Mild‐moderate 

Severe 

Severe ‐ 

complicated 

WBC < 15,000 cell/mcL and a 

serum creatinine level < 1.5 

times premorbid level 

WBC ≥ 15,000 cell/mcL or 

serum creatinine level ≥ 1.5 

times premorbid level 

Hypotension, shock, 

ileus, megacolon 

Methods 

• Descriptive, retrospective chart review 

Metronidazole 500mg PO q8h 

for 10 ‐ 14 days 

Vancomycin 125 mg PO q6h 

for 10 ‐ 14 days 

Vancomycin 500 mg PO q6h + 

metronidazole 500 mg IV q8h 

• Subject population 

– Age ≥ 18 years diagnosed July 1, 2009 – June 30, 2011 

– CDI treatment initiated at LGH 

• Assessment 

– Severity categorized based on clinical signs and symptoms 

– Initial treatment compared to recommended therapy 

• Evaluated for adherence 

• Classified as under, appropriate, or overtreatment 

Definitions 

• Clinical cure: no need for therapy escalation; resolution of 

diarrhea by day 6; and subject survival 

• Recurrence: positive stool toxin assay within 90 days of initial 

positive stool toxin assay 

• Mortality: subject expired from any cause within 90 days of 

positive stool toxin assay 

• Antimicrobial use: use of at least one dose of an antimicrobial 

in the eight weeks prior to the positive stool toxin assay 

Current Study 

• Rationale 

– Anecdotal evidence suggested physician non‐adherence 

– Concern regarding undertreatment of patients 

• Purpose 

– To determine if physicians were adherent to the ALGH CDI 

guidelines 

– To determine if adherence to the guidelines improved 

patient outcomes 

Endpoints 

• Primary endpoint: percentage of subjects who were 

treated in accordance with CDI guidelines 

• SSecondary d endpoints d i t 

– Incidence of under, appropriate, and overtreatment 

– Incidence of clinical outcomes in treatment groups 

– Impact of proton pump inhibitor or prior antimicrobial use 

on CDI severity 

Statistics 

• Descriptive study required 130 subjects for 80% power 

for the primary endpoint 

• Pearson Chi‐Square / Fisher’s exact tests used to analyze 

q / y 

group differences 

– Two‐tailed p value < 0.05 considered statistically significant for 

single comparisons 

– Two‐tailed p value < 0.02 considered statistically significant for 

multiple comparisons (Bonferroni’s method) 

8/29/2012 

2

650 subjects 

id identified tifi d 

Results 

250 subjects 

randomly 

selected 

324 encounters 

evaluated l t d 

Baseline Characteristics: Encounters 

Encounters [n = 324] No (%) 

Initial Episode 220 (67.7) 

1st 1 recurrence 56 (17.3) 

2nd recurrence 10 (3.1) 

3rd recurrence 5 (1.5) 

Reinfection 33 (10.2) 

Severity [n = 324] No (%) 

Mild‐moderate Mild moderate 163 (50.3) 

Severe 105 (32.4) 

Severe‐complicated 56 (17.3) 

Mild‐moderate Treatment Regimens 

Regimen [n = 163] No (%) 

Metronidazole 500 mg PO q8h 66 (40.5) 

Metronidazole 500 mg IV q8h 22 (13.5) 

Vancomycin 125 mg PO q6h * 51 (31.3) 

Metronidazole 500 mg IV q8h + 

vancomycin 125 mg PO q6h 

13 (8) 

Other 11 (6.7) 

* Appropriate depending on 

subject’s history of illness. 

Baseline Characteristics: Subjects 

Characteristics [n = 250] 

Female [no (%)] 141 (56.4) 

Age [mean (SD), range] 67.83 ± 17.36 (18 – 100) 

Ethnicity [no (%)] 

Caucasian 

African‐American 

Asian 

Hispanic 

210 (84) 

13 (5.2) 

12 (4.8) 

7 (2.8) 

History of CDI [no (%)] 18 (7.2) 

Adherence Rates 

No (%) 

Overall [n = 324] 137 (42.3) 

Mild‐moderate [n = 163] 86 (52.8) 

Severe [n = 105] 41 (39) 

Severe‐complicated [n = 56] 10 (17.9) p < 0.001 

Mild‐moderate Treatment Regimens 

8/29/2012 

3

Severe Treatment Regimens 


Metronidazole 500 mg PO q8h 19 (18.1) 

Metronidazole 500 mg IV q8h 17 (16.2) 

Vancomycin i 125 mg PO q6h h 41 ( (39) ) 



15 (14.3) 



7 (6.7) 

Other 6 (5.7) 

Severe‐complicated Treatment Regimens 


Metronidazole 500 mg IV q8h 8 (14.3) 

Vancomycin 125 mg PO q6h 12 (21.4) 

Metronidazole 500 mg g IV q8h q + 


16 (28 (28.6) 6) 



5 (8.9) 



10 (17.9) 

Other 5 (8.9) 

Overall Treatment Regimens 

Severe Treatment Regimens 

Severe‐complicated Treatment Regimens 

Undertreatment versus Appropriate Treatment 

Escalation 

required 

Overall 

[n = 324] 

No (%) 

Undertreatment 

[n = 85] 

No (%) 

Appropriate 

treatment 

[n = 149] 

No (%) 

Percent 

difference 

83 (25.6) 29 (34.1) 41 (27.5) + 6.6 

Clinical cure 178 (54.9) 35 (41.2) 83 (55.7) ‐ 14.5 * 

Mortality 43 (13.3) 21 (24.7) 15 (10.1) + 14.6 

Recurrence free 224 (69.1) 47 (55.3) 112 (75.2) ‐ 19.9 

p < 0.02 

* p = 0.033 

8/29/2012 

4

Overtreatment versus Appropriate Treatment 

Escalation 

required 

Overall 

[n = 324] 

No (%) 

Appropriate 

treatment 

[n = 149] 

No (%) 

Overtreatment 

[n = 90] 

No (%) 

Percent 

difference 

83 (25.6) 41 (27.5) 13 (14.4) ‐ 13.1 

Clinical cure 178 (54.9) 83 (55.7) 60 (66.7) + 11.0 

Mortality 43 (13.3) 15 (10.1) 7 (7.8) ‐ 2.3 

Recurrence free 224 (69.1) 112 (75.2) 65 (72.2) ‐ 3.0 

p < 0.02 

Prior Antimicrobial Use 

Antimicrobial use in 

Severity 

previous 8 weeks 

No (%) 

Overall [n [ = 324] ] 239 (73.8) ( ) 


Severe [n = 105] 79 (75.2) 

Severe‐complicated [n = 56] 39 (69.6) p = 0.81 

Conclusions: Primary Endpoint 

• 42 % overall adherence to CDI guideline 

• Adherence lower in severe and severe‐complicated CDI 

• Barriers to adherence 

– Lack of awareness among hospital staff 

– Subjects unable to take medications by mouth 

– Barriers to using rectal vancomycin 

– Clinically severe subjects with low WBC count 

Proton Pump Inhibitor Use 

Used proton 

Severity 

pump inhibitor 

No (%) 

Overall [n [ = 324] ] 235 (72.5) ( ) 


Severe [n = 105] 73 (69.5) 

Severe‐complicated [n = 56] 46 (82.1) p = 0.16 

• Retrospective study 

• Researcher bias 

Limitations 

• Strict adherence to guideline definitions 

• Study not powered to analyze secondary endpoints 

Conclusions: Secondary Endpoints 

• Undertreatment versus appropriate treatment 

– Significantly increased incidence of mortality and recurrence 

– Lower incidence of clinical cure 

• Overtreatment versus appropriate treatment 

– Failed to show significant improvement in clinical outcomes 

– Potentially leads to increased medication costs and adverse 

effects 

• Proton pumps inhibitor and prior antimicrobial use was 

not significantly different between severity groups 

8/29/2012 

5

Patient Case 

RW is a 37‐year old female with no significant past 

medical history who is admitted to the hospital for 

three days of diarrhea after a seven day treatment 

course of moxifloxacin for community‐acquired 

pneumonia. RW’s symptoms include a white blood 

cell count of 13.0 cells/mm 3 , serum creatinine (Scr) 

of 0.7 g/dL, and a positive stool toxin assay for CDI. 

Based on RW’s severity of illness, please 

select the most appropriate treatment 

option from the list below. 

A. Oral vancomycin 125 mg 

every 6 hours for 14 days 

B. Oral metronidazole 500 mg 


C. Oral vancomycin 250mg 


D. Intravenous metronidazole 

500 mg every 8 hours PLUS 

oral vancomycin 500 mg 


Oral vancomycin 125 mg... 

0% 0% 0% 0% 

Oral metronidazole 500 .. 

Oral vancomycin 250mg ... 

Intravenous metronidazo.. 

Based on RW’s symptoms, what is her 

severity of illness? 

A. Mild‐moderate 

B. Mild‐moderate, , 

complicated 

C. Severe 

D. Severe, complicated 

Mild‐moderate 

0% 0% 0% 0% 

Mild‐moderate, compli... 


Adherence to and Outcomes 

Associated with a Clostridium 

difficile Infection Guideline at a 

Large Teaching Institution 



Severe 

Severe, complicated 

8/29/2012 

6

Adherence to and Outcomes Associated with a Clostridium 

difficile Infection Guideline at a Large Teaching Institution 


Background: The incidence and severity of Clostridium difficile infection (CDI) is on the rise with reports 

of devastating health outcomes. National CDI treatment guidelines stratify patients based on clinical 

symptoms and recommend specific treatment based on severity of illness. In 2009, Advocate Lutheran 

General Hospital adopted guidelines with identical treatment algorithms. The purpose of this project 

was to determine if patients were being treated in accordance with the CDI guidelines and whether 

adherence affected patient outcomes. 

Methods: This was a retrospective, descriptive study. Subjects were identified by CDI‐associated ICD‐9 

codes from July 1, 2009 to June 30, 2011. Subjects were stratified by disease severity based on 

laboratory values and symptoms. Guideline adherence was assessed based on initial treatment 

selection and subjects were categorized as undertreated (UT), overtreated (OT), or appropriately 

treated (AT) accordingly. Secondary endpoints included need for therapeutic escalation, clinical cure, 

recurrence rates, 90‐day all‐cause mortality, proton pump inhibitor (PPI) and antimicrobial use. 

Results: Two hundred fifty subjects with 324 encounters were analyzed. Overall guideline adherence 

rate was 42.3%. Adherence rates by severity: mild‐moderate, 52.8%; severe, 39.0%; and severe‐ 

complicated, 17.9% (p < 0.001). 46% of subjects were AT, 27.8% were OT, and 26.2% were UT. Clinical 

outcomes between UT versus AT subjects: therapeutic escalation required, 34.1% vs. 27.5%; clinical 

cure, 41.2% vs. 55.7%; mortality, 24.1% vs. 10.1%; and recurrence, 44.7% vs. 24.8%. Clinical outcomes 

between OT versus AT subjects: therapeutic escalation required 14.4% vs. 27.5%; clinical cure, 66.7% vs. 

55.7%; mortality, 7.8% vs. 10.1%; recurrence, 27.8% vs. 24.8%. PPI or antimicrobial use did not affect 

severity of illness. 

Conclusions: The majority of subjects were not treated in accordance with the CDI guidelines, 

particularly those with severe and severe‐complicated illness. UT subjects had worse clinical outcomes 

compared to their AT counterparts whereas, OT subjects failed to show significant improvements in 

clinical outcomes compared to AT subjects. Emphasis should be placed on CDI guideline adherence as 

this results in improved outcomes.


A pilot multidisciplinary team to monitor 

controlled substance documentation in a 

community hospital 

Tim Humlicek, PharmD 

PGY2 Solid Organ Transplant Pharmacy Resident 


Chicago, IL 


• Outline the process of interpreting controlled 

substance reports generated from automated 

dispensing machines that can identify hig risk 

users users. 

• Recognize potential controlled substance 

diversion episodes using electronic medication 

administration documentation 

Regulations 

• Drug Enforcement Administration (DEA) 

– Enforces the Controlled Substance Act 

– Employee pilferage and units lost in transit: 

• 22.7% of all unaccounted oxycodone in 2000‐2003 

• Joint Commission Standard MM.4.80 

– Requires processes to address diversion 

prevention and account for all unused, expired, 

or returned medications. 

1. Drug Enforcement Administration. Oxycodone theft & loss incidents: January 2000 through June 2003. 

http://www.deadiversion.usdoj.gov/drugs_concern/oxycodone/oxylosses_oct2003_1.pdf. Accessed July 28, 2011 

2. Keenly P, Uselton JP. Maintain Compliance with Joint Commission Medication Management Standards. 

http://www.psqh.com/julaug08/medication.html. Accessed July 28, 2011. 

Disclosure 

The author of this presentation has no actual or potential 

conflicts of interest. 

NorthShore University HealthSystem 

• Four acute care hospitals 

– Evanston Hospital: 354 beds 

– Glenbrook Hospital: 169 beds 

– Highland Park Hospital: 149 beds 

– Skokie Hospital: 195 beds 

• NorthShore Medical Group 

• NorthShore Research Institute 

• NorthShore Foundation 

Health System Diversion 

• Diversion: unlawful 

channeling of regulated 

pharmaceuticals from 

legal sources to illicit 

market – Multi 

• Opportunities 

– Destruction/Waste 

– Intrahospital transfer 

– Large Large‐volume volume removals 

Multi‐dose dose vials 

– Patient specific items 

– Point of purchase 

– Unauthorized removals 

Inciardi JA et al. Mechanisms of Prescription Drug Diversion Among Drug-Involved Cluband 

Street-Based Populations..Pain Med. 2007;8(2):171-183 

O’Neal B, Siegel J. Diversion in the Pharmacy. Hosp Pharm. 2007;42(2):145-148 

8/29/2012 

. 

1

Background 

• Lack of comprehensive published guidelines 

– Available recommendations: 

• Multidisciplinary teams 

• Monitoring in operating rooms 

• Investigative process 

• Drug diversion software 

• Intervention process 

O’Neal B, Siegel J. Diversion in the Pharmacy. Hosp Pharm. 2007;42(2):145-148 

Siegel J, Wierwille C, O’neal B. The Investigative Process. Hosp Pharm. 2007:42(2);466469 

Siegel J, O’Neal B. Code N: Multidisciplinary Approach to Proactive Drug Diversion Prevention. Hosp 

Pharm. 2007:42(2);244-248 

Project Objectives 

• Primary: 

– Develop and implement a standardized process to 

identify users with risk of controlled substance 

diversion 

Monthly 

Report 

Methods 

•Pharmacist to upload monthly ADM data to vendor 

•Pharmacist organizes vendor report to identify high risk users 

•Pharmacist prints controlled substance removals from previous 30 

days for identified users 

UUser AAudit di • NNurse Manager M audits di transactions i for f appropriate i ddocumentation i 

Follow Up 

•Users with potential diversion episodes are assessed by pharmacist 

and nurse manager for further diversion risks 

Background 

• University Health System Consortium Survey 

– Operating Room Practices: 44‐63% reconciled 

against dispensing records 

– Use of diversion software: 79% 

• “Sometimes” or “Always” investigate flagged individuals 

identified by software: 88‐99% 

– Discrepancies “always” investigated: 92‐98% 

McClure SR, O’Neal BC, Grauer D, Couldry RJ, King AR. Compliance with Recommendations for 

Prevention and Detection of Controlled-substance Diversion in Hospitals. Am J Health-Syst Pharm. 

2011;68(8):689-94. 

Project Objectives 

• Secondary: 

– Quantify potential controlled substance diversion 

opportunities in users with identified risk of 

controlled substance diversion 

– Assess the type of controlled substance 

discrepancies occurring based on controlled 

substance documentation 

Methods: Identifying Users 

Report 1: Compares removals of all controlled substances 

by one user to all users 

Report 2: Compares all removals of given controlled 

substance by one user to all users of same ADM 

Report 3: Compares removals of given 

controlled substance by one user to all 

users of that class/medication 

Report 4: Compares daily average removals 

for one user for 

given controlled substance 

to all users of same 

ADM 

8/29/2012 

2

Methods: Identifying Users Users 

• Report 1: Users with >3 SDs (SD) above the mean removal of any controlled 

substance 

AND 

• Report 2: Users with >2 SD above mean compared to station level peers for given 

class of controlled medications 

AND 

• Report 3: Users with >2 SD above mean compared to all hospital users for given 

class of controlled medications 

AND 

• Report 4: Users with >2 SD above mean compared to station level peers on a 

daily basis for given class of controlled medications 

Behavioral Indicators 

Methods: User Audit 

• Isolates self 

• Frequent disappearances 

• Unscheduled visits 

• Vl Volunteers t ffor additional dditi l shifts hift 

• Frequently spills/wastes narcotics 

• Chaotic home life 

• Refused compliance with 

investigations 

Patient Care Indicators 

• Incorrect charting 

• Inconsistent work quality 

• Offers to help other nurses’ 

patients 

• Removes excessive amounts of 

narcotics 

• Requests specific patients 

• Inadequate pain control with 

patients 


Pharm. 2007:42(2);244-248 

Methods: Discrepancy Audit 

• Controlled substance discrepancies were reviewed over the 

same period assessing for type and severity 

– Level 1: Miscounting 

– Level 2: Mechanical error 

– Level 3: Inappropriate pp p documentation 

– Level 4: Incorrect administration 

– Level 5: Inadequate resolution 


• Users had all removals of controlled substances in previous 30 

days audited for documentation and potential diversion 

episodes: 

– Removal without order 

– Removal without documented administration 

– Removal in excess of order that does not require waste 

– Removal in excess of order that requires waste without appropriate 

waste documentation 


Number marked “Yes” Level of Risk 

0‐2 Points Low 

3‐4 Points Medium 

>5 Points High 


Pharm. 2007:42(2);244-248 

Results 

Indicator Nov. 2011 Dec. 2011 Jan. 2012 Feb. 2012 

Doses Dispensed‐ ADM 62,016 60,049 59,784 54,918 

Average Daily Doses‐ADM 2,067 1,937 1,929 1,894 

C‐II to C‐V Dispense 5,208 4,348 3,788 3,649 

% C‐II to C‐V 8.40% 7.24% 6.34% 6.64% 

Total C‐II to C‐V 

Discrepancies 

42 36 29 13 

% C‐II to C‐V Discrepancies 0.81% 0.83% 0.77% 0.36% 

Total Overrides 2,938 3,137 3,015 1,995 

C‐II to C‐V Overrides 891 931 897 623 

% C‐II to C‐V Overrides 1.44% 1.55% 1.50% 1.13% 

8/29/2012 

3

Results Results‐User User Audits 

Nov. 2011 Dec. 2011 Jan. 2012 Feb. 2012 

Total Users Audited 5 7 5 5 

Total Transactions 

Audited 

147 362 174 277 

Transactions Per User 29.4 51.7 

Appropriate Documentation 

34.8 55.4 

Appropriate pp p Record of 


147/147 (100%) 357/362 

(98.6%) 

168/174 

(95.9%) 

274/277 

(98.9%) 

Inappropriate Documentation 

Removals without 

order 

0 0 0 0 

Removals without 


0 5 6 3 

Excess removals 0 0 0 0 

Required 

wasting/return 

without 

documentation 

0/18 0/39 0/29 0/43 

Results: Potential Diversion Episodes 

• Six (27.3%) of the users who were audited and 

14 (1.1%) of transactions had a potential 

diversion episode 

• Reviews between pharmacist and nurse 

manager yielded low suspicions of diversion 

based on behavioral and patient care 

indicators 

Discussion 

• Most transactions of controlled substances 

had appropriate documentation 

• Potential diversion episodes were all due to 

lack of documented administration 

• Variable quantity and severity of discrepancies 

occurred 

Results 

• Characteristics of users (n=22) 

– Medical: 13(59.1%) 

– Surgical: 5 (22.7%) 

– Telemetry: 2 (9.1%) (9 1%) 

– Anesthesia: 1 (4.5%) 

– Intensive Care/Emergency: 1 (4.5%) 

Results Results‐Discrepancies 

Discrepancies 

Limitations 

• Detection of diversion dependent on documentation 

practices 

– Endpoints rely on mistakes of high volume users 

• Inclusion criteria 

– Low threshold for inclusion means more users were audited than 

necessary 

• External Validity 

– Variable workplace practices may limit extrapolation of results to 

other health systems 

8/29/2012 

4

Future Directions 

• Specify audits for users with highest removals 

• Establish protocol for investigating potential diversion 

episodes in users with medium‐high risk: 

– Establish level of suspicion for prioritizing further interventions 

• Implement use of refined methods across health‐system 

health system 

SELF ASSESSMENT QUESTION 

#1 

SELF ASSESSMENT QUESTION 

#2 

Conclusions 

• Using objective criteria from usage reports is capable of 

identifying users with disproportionate removals of controlled 

substances 

• Subjective knowledge of employees is another important 

aspect of diversion monitoring 

• Appropriate documentation occurred most frequently 

• Potential diversion episodes lacked an documented 

administration, but could have been administered by another 

user 

• Discrepancy quantity and severity may be useful as a 

benchmark to track documentation practices 

Which of the following users meets at least one criteria to be eligible for 

a controlled substance transaction audit? 

a) A user with a monthly average of removals less than 3 SDs of the mean for a 

particular controlled substance compared to all hospital users 

b) A user with a daily average removals less than 2 SDs above the mean for a 

particular controlled substance compared to all users of a specific automated 

dispensing machine 

c) A user with a monthly average of removals less than 2 SDs above the mean 

compared to all users of a particular automated dispensing machine 

d) A user with a monthly average of removals greater than 3 SDs of the mean for a 

particular controlled substance compared to all hospital users 

Which of the following could be considered a potential controlled substance 

diversion episode? 

a) Removal of a controlled substance and a documented patient refusal 

and an appropriate record of return 

b) Removal of a controlled substance without an order 

c) Removal of a controlled substance with a documented administration to 

a patient p 

d) Canceled removal of a controlled substance with subsequent 

documented administration 

8/29/2012 

5

Special thanks to: 

• Carol Heunisch, PharmD, BCPS 

• Nancy Lechowicz, RN, MS 

• Monica Sherlock, Sherlock RN RN, MSN 

• Rita Walter, RN, MS 

• Mary Keegan, RN, MS 

Questions? 

Contact Information: 

Tim Humlicek, PharmD 


timothy timothy_j_humlicek@rush.edu 

j humlicek@rush edu 

References 

1. Drug Enforcement Administration. http://www.justice.gov/dea/ . Accessed July 31, 2011. 

2. Drug Enforcement Administration. Oxycodone theft & loss incidents: January 2000 through June 

2003. http://www.deadiversion.usdoj.gov/drugs_concern/oxycodone/oxylosses_oct2003_1.pdf. 

Accessed July 28, 2011 

3. Keenly P, Uselton JP. Maintain Compliance with Joint Commission Medication Management 

Standards. http://www.psqh.com/julaug08/medication.html. Accessed July 28, 2011. 

4. Inciardi JA et al. Mechanisms of Prescription Drug Diversion Among Drug‐Involved Club‐and 

Street‐Based Populations..Pain Med. 2007;8(2):171‐183 

5. O’Neal B, Siegel J. Diversion in the Pharmacy. Hosp Pharm. 2007;42(2):145‐148 

66. McClure SR SR, O’neal O neal BC BC, Grauer D, D Couldry RJ RJ, King AR AR. Compliance with Recommendations for 

Prevention and Detection of Controlled‐substance Diversion in Hospitals. Am J Health‐Syst 

Pharm. 2011;68(8):689‐94. 

7. Siegel J, Wierwille C, O’neal B. The Investigative Process. Hosp Pharm. 2007:42(2);466‐469 

8. Siegel J, O’Neal B. Code N: Multidisciplinary Approach to Proactive Drug Diversion Prevention. 

Hosp Pharm. 2007:42(2);244‐248 

8/29/2012 

6


Prolonged Antibiotic Prophylaxis After 

Cardiovascular Implantable Electronic 

Device Implantation and Its Effect on 

Device‐Related Infections 

Background 

Natasha Lopez, PharmD, BCPS 

Critical Care Pharmacist 


Chicago, IL 

• Cardiac implantable electronic device (CIED) infections 

have remained a major complication after implantation 

• The incidence of infection related to CIED implantation 

ranges from 0.13% to 19.9% 

• Variations in the populations and practices at different 

sites account for this range of incidence rates 

• With the expanded indications for CIED implantation and 

higher risk patient population receiving therapy, the 

prevention and management of CIED infections 

continues to be studied 

DiMarco, et al. NEJM. 2003;349:1836‐1847. 

Risk Factors 

Patient Factors Procedural Characteristics 

•Diabetes mellitus 

•Heart failure 

•Malignancy 

•Renal R lddysfunction f i (glomerular ( l l 

filtration rate

Antibiotic Prophylaxis 

American Heart Association (AHA) 

• Preoperative prophylaxis with an antibiotic that has 

in vitro activity against staphylococci should be 

administered (Level of Evidence: A) 

• Antimicrobial prophylaxis in the postoperative period 

is not recommended due to lack of evidence and risk 

of adverse drug events and antimicrobial resistance 

Baddour L, et al. Circulation. 2010;121:458‐477. 

Study Purpose 

• To determine if postoperative antibiotic prophylaxis 

with cephalexin administered for 72 hours reduces 

the incidence of infection in patients undergoing 

CIED procedure 

Research Hypothesis 

• There is no difference in the incidence of CIED infection 

between 72 hour postoperative cephalexin and no 

postoperative antibiotic regimens 

Methods‐ Outcomes 

Endpoint 

Primary Compare the incidence of CIED related infections 

between 72 hour postoperative cephalexin to no 

postoperative antibiotics 

Secondary •Identify the patient characteristics that correlated with 

the primary outcome 

•Time to infection 

Background 

• At Rush University Medical Center (RUMC), 72 hours 

of postoperative prophylactic antibiotics are used 

after CIED implantation 

• Currently no study has specifically examined the 

efficacy of postoperative antibiotic prophylaxis in 

this patient population 

Methods ‐ Design 

• Retrospective chart review 

– January 2007 – October 2011 

• Single center, Rush University Medical Center 

– 673 bed, university affiliated medical center 

Methods‐ Patient Population 

Inclusion criteria Exclusion criteria 

• Age ≥ 18 and < 89 years • Documented penicillin and/or 

cephalosporin allergy 

• Recipients of a new, upgrade, 

generator replacement revision 

or lead revision of CIED 

• Received antibiotics for another 

iindication di ti prior i to t CIED 

•Received preoperative 

antibiotics with cefazolin prior to 

CIED procedure 

• Pregnancy 

• Patients who underwent 

thoracotomy with implantation 

8/29/2012 

2

Methods‐ Data Collection 


– Age 

– Gender 

– Comorbidities 

– LVEF 

• Procedure factors 

– CIED type 

– Leads 

– Length of procedure 

• Medication 

– Anticoagulants 

– Immunosuppressants 

Patient Characteristics 

• Outcomes 

– Device Infection 

– Cultures 

• Culture positive 

• Culture negative 

– Time to infection 

– Organism identified 

• Gram positive 

• Gram negative 

– Susceptibilities 

Characteristics CIED 

(n=155) 

Age (years), median (IQR) 63 (54‐74) 

Male sex, no. (%) 95 (61.3) 

Weight (kg), median (IQR) 

Ethnicity, no. (%) 

81.6 (68.9‐97.1) 

African American 

80 (51.6) 

Caucasian 51 (32 (32.9) 9) 

LVEF (%), median (IQR) 25 (15‐35) 

SCr (mcg/dL), median (IQR) 1.1 (0.9‐1.4) 

Co‐morbidities, no. (%) 

Atrial fibrillation/flutter 

COPD 

CHF 

CKD 

Diabetes 

HTN 

Results‐ Infections 

• Incidence of Infection= 2.6 % 

Infection 

(n=4) 

Time to 

infection 

(days) 

Organism Procedure 

(prior to 

infection) 

1 28 Culture negative Upgrade CRT‐D‐ 

3 leads 

2 48 Culture negative Generator ICD‐ 

replacement 2 leads 

3 24 Staphylococcus aureus 

(MSSA) 

4 128 •Pseudomonas 

aeruginosa 

•Klebsiella pneumoniae 

(pan‐susceptible) 

54 (34.8) 

32 (20.6) 

108 (69.7) 

47 (30.3) 

49 (31.6) 

128 (82.5) 

Device Treatment 

Levofloxacin & 

clindamycin x14 d 

replacement 2 leads 

Vancomycin + 

piperacillin/tazo 

x14 d 

Atrial lead 

revision & 

generator 

replacement 

PPM‐ 

2leads 

Upgrade ICD‐ 

2 leads 

Cefazolin x14 d 

Vancomcyin + 

Cefepime x14 d 

Levofloxacin x7 d 

Duration= 21 d 

Patient Population 

Cephalexin x72 hours 

(n= 155 ) 

ICD 9 Codes 

CIED implants (n=615 ) 

Inclusion 

‐Age >18 and < 89 years 

‐Recipient of new implanted CIED 

*revised, upgrade, generator replaced 

Exclusion 

N= 460 

Erx code: cephalexin 

Patient Characteristics 

•No preoperative abx or 

received vancomycin 

•Documented penicillin and/or 

cephalosporin allergy 

•Received antibiotics for 

another indication 

•Pregnancy 

No post‐operative 

cephalexin 

(n= 0) 

Characteristics CIED 

(n=155) 

Length of procedure (mins), median 78:52 

Cefazolin preoperative dose (grams), median (IQR) 1 (1‐2) 

Cumulative cefazolin (grams), median (IQR) 3 (3‐5) 

•New CIED , no. (%) 

112 (72.3) 

PPM 

37(23.9) 

ICD 

53(34.2) 

CRT CRT‐DD 22( 14.2) 14 2) 

•Lead Revision 

4 (2.6) 

•Upgrade 

16 (10.3) 

•Generator replacement 

15(9.7) 

•Lead revision and Generator replacement 

8 ( 5.2) 

•Temporary pacing wire, no. (%) 

•Leads placed, no. (%) 

11 (7.1) 

2 

42 (27.7) 

PPM= Permanent pacemaker ICD= implantable cardiac defibrillator 

CRT‐D= Cardiac resynchronization therapy with defibrillator 

Results‐ Characteristics of Patients with 

CIED Infection 

Infection 

(n=4) 

Age, 

yr 

Sex DM CKD COPD History of 

Valve 

repair 

1 62 M _ _ _ 

Oral 

anticoagulant 

+ + 

Immunosuppressant 

2 29 M _ _ _ _ _ _ 

3 85 M 

+ + 

4 53 F _ _ 

_ , Absent; +, Present 

M= male; F= female 

_ _ 

+ 

+ + + 

_ 

_ 

_ 

8/29/2012 

3

Study Limitations 

• Dependent on consistency and completeness 

of medical charts 

• ICD‐9 9 code d ddependent d id identification ifi i of f 

patients with new CIED and infection 

• Selection and dosing of medications by 

prescriber bias 

Future Application 

• Vancomycin comparison group 

• Review of postoperative antibiotic prophylaxis 

regimen prior to 2007 

• Prospective evaluation of infection rate 

Self‐Assessment Questions 

Common organisms responsible for CIED 

infections include all of the following, EXCEPT? 

AA. CCoagulase‐negative l ti St Staphylococcus h l 

B. Methicillin resistant Staphylococcus aureus 

C. Methicillin sensitive Staphylococcus aureus 

D. Candida species 

19 

Conclusion 

• Previous studies utilizing only preoperative 

antibiotic prophylaxis document a 0.5‐1% 

incidence of infection 

• Currently data are insufficient to confidently assess 

postoperative antibiotic prophylaxis after CIED 

procedures 

• The existing data does not allow definitive 

recommendations for clinical practice 

Self‐Assessment Questions 

Which of the following is recommended by the 

2010 American Heart Association Guidelines to 

prevent CIED infections at time of device 

implantation? 

A. Preoperative antibiotic prophylaxis 

B. Preoperative and 72 hour postoperative antibiotic 

prophylaxis 

C. 72 hour postoperative antibiotic prophylaxis 

D. No antibiotic prophylaxis 


Prolonged Antibiotic Prophylaxis After 

Cardiovascular Implantable Electronic 

Device Implantation and Its Effect on 

Device‐Related Infections 

Researcher: 

Natasha Lopez, PharmD, BCPS 

Research Committee: 

Christopher Crank, PharmD, Ms, AQ‐ID 

Payal Gurnani, PharmD, BCPS 

8/29/2012 

4


From Dabigatran to Warfarin: A 

Change in Progress 

Ashley Jacobs, Pharm.D. 


Lutheran Health Network 

Fort Wayne, IN 

September 2012 

Disclosure: The speaker has no actual or potential conflict of interest in relation to this presentation. 

Dabigatran and Warfarin 

Dabigatran Warfarin 

• Pros 

– No routine monitoring 

required 

– SStandard d dd dosages available il bl 

• Cons 

– No antidote available 

– Post‐marketing reports of 

bleeding 

• Pros 

– Therapy can be tailored to 

patient specific needs 

– Long history of use 

– Antidote available 

• Cons 

– Routine monitoring required 

– Difficulty managing unstable 

INRs 

– Bleeding 

Heartwire. Available at: http://www.theheart.org/article/1324923.do 

Warfarin [Prescribing Information]. Haifa Bay, Israel: Taro Pharmaceutical Industries Ltd; 2009. 

Pradaxa® [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2012 

Adverse Events in the RE‐LY Study 

•In the RE-LY study, bleeding and 

gastrointestinal events (ex: dyspepsia and 

gastrointestinal hemorrhage) were the most 

frequent causes of dabigatran treatment 

discontinuation 

Connolly SJ, Ezekowitz MD, et al. N Engl J Med 2009; 361:1139‐51. 

Pradaxa® [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim 

Pharmaceuticals, Inc.; 2012. 

Common Oral Anticoagulants 

• Warfarin: A vitamin‐K antagonist whose 

indications include prevention of 

thromboembolic events in atrial fibrillation 

• Dabigatran: A direct thrombin inhibitor 

approved to reduce the risk of systemic 

embolism and stroke in patients with non 

valvular atrial fibrillation 

Warfarin [Prescribing Information]. Haifa Bay, Israel: Taro Pharmaceutical Industries Ltd; 2009. 

Pradaxa® [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2012. 

RE‐LY: Warfarin vs. Dabigatran 

• The Randomized Evaluation of Long‐Term 

Anticoagulation Therapy (RE‐LY) study 

compared dabigatran 110 mg BID and 150 mg 

BID to dose‐adjusted dose adjusted warfarin 

– Primary outcome event was stroke or systemic 

embolism 

– Dabigatran 150 mg BID had lower rates of stroke 

or systemic embolism, but similar rates of major 

hemorrhage, when compared to warfarin 

Dabigatran 

Connolly SJ, et al. N Engl J Med 2009; 361:1139-51 

• Approved in the Fall of 2010 with the following 

dosing recommendations: 

• CrCl >30: 150 mg PO BID 

• CrCl 15 to 30: 75 mg PO BID 

• CrCl

Study Background 

• Observation of patients previously treated with 

dabigatran being switched to warfarin 

– Pharmacist managed Lutheran Hospital Anticoagulation 

Clinic 

– Inpatients 

Methods 

• Patient interviews and retrospective chart reviews at the 

Lutheran Hospital Anticoagulation Clinic and Lutheran 

Hospital 

• Potential causes of dabigatran treatment discontinuation 

evaluated include: failure of therapy, therapy adverse drug events, events 

and cost of therapy 

• Patients were selected from the time dabigatran was 

released in Fall 2010 until April 2012 

Duration of Dabigatran Therapy 

• Average treatment duration: 4 months 

½ month 

12.5% 

12 months 

12.5% % 

Duration of dabigatran therapy (N=8) 

9months 

12.5% 

5 months 

25% 

1 month 

37.5% 

Objective 

• To determine reasons for discontinuation of 

dabigatran and re‐initiation or initiation of 

warfarin in a real‐world setting 

Patient Demographics 

Results 

Number of Patients 22 

Inpatients 9 

Outpatients 13 

Gender Men: 55% 

Women: 45% 

Age Average: 76 

Max: 93 

Min: 34 

• Some patients had more than one reason for 

discontinuation of therapy 

6 

5 

4 

3 

2 

1 

0 

Summary of Reasons for 

Discontinuation 

Number of Claims 

Number of Claims 

8/29/2012 

2

Reasons for Discontinuation 

• Gastrointestinal Side Effects 

– Diarrhea 

– Heartburn 

– Upset stomach 

• Off‐label Indications 

– DVT prophylaxis and aortic stenosis 

• Clot Formation 

– Patient admitted with a PE 

Comparison of Results 

RE‐LY Study Current Study 

• Overall rate of 

discontinuation: 15.5% 

– Discontinuation due to 

gastrointestinal symptoms 

• 130 patients (2.1%) 

Evaluation 

• Total number of Lutheran 

Medical Group patients 

prescribed dabigatran: 66 

– Rt Rate of f discontinuation di ti ti for f 

the current study: 25% 

– Discontinuation due to 

gastrointestinal symptoms 

• 3 patients (14%) 

Connolly SJ, Ezekowitz MD, et al. N Engl J Med 2009; 361:1139‐51 

• Limitations 

– Small sample size 

– We do not have a baseline value to compare our 

data to because we do not know the percentage 

of patients currently on warfarin, who were 

initially on dabigatran 

Cost Comparison 

Dabigatran 

Warfarin 

• Cash price for 150 mg BID • Anticoagulation Clinic visit 

30 day supply at certain 

– Visit: $68.48 

pharmacies 

– Finger stick: $8.55 

– $266.32 • Cash price for warfarin 30‐ 

day supply at certain 

pharmacies 

– $4 

Evaluation 

• Benefits 

– Results provided an opportunity for pharmacists 

to educate prescribers about dabigatran and what 

to consider prior p to initiating g therapy py 

• Ex: Evaluate the patient’s age and past medical history 

before prescribing dabigatran 

– Adverse events were identified that can be 

reported 

Conclusion 

• Considerations for dabigatran initiation 

– Cost, age, renal function, and a patient’s 

willingness to handle gastrointestinal side effects 

need to be taken into account 

8/29/2012 

3

A patient has a CrCl of 25 mL/min. Which dose of 

dabigatran should be prescribed for this patient? 

– A: 150 mg PO daily 

– B: 75 mg PO BID 

– C: 150 mg PO BID 

– D: Dabigatran is 

contraindicated in 

this patient 

References 

A: 150 mg PO daily 

0% 0% 0% 0% 

B: 75 mg PO BID 

C: 150 mg PO BID 

D: Dabigatran is contrai... 

• 1. MayoClinic. Atrial Fibrillation. Available at: http://www.mayoclinic.com/health/atrial‐fibrillation/DS00291 Accessed 

November 27, 2011. 

• 2. Boehringer Ingelheim Pharmaceuticals, Inc. How AFib can cause a stroke. Available at: https://www.afibstroke.com/blood‐ 

clot‐causes‐ 

stroke.jsp?sc=PRDACQWEBGGLDDG1203103&utm_source=google&utm_medium=cpc&utm_term=afib&utm_campaign=Afi 

b_Unbranded Accessed April 7, 2012. 

• 3. Warfarin [Prescribing Information]. Haifa Bay, Israel: Taro Pharmaceutical Industries Ltd; 2009. 

• 4. Pradaxa® [Prescribing Information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2012. 

• 5. Connolly y SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran g versus warfarin in ppatients with atrial fibrillation. N Engl g J Med 2009; 

361:1139‐51. 

• 6. Boehringer Ingelheim Pharmaceuticals, Inc. Pradaxa. Available at: http://www.pradaxa.com/ Accessed April 7, 2012. 


From Dabigatran to Warfarin: A 

Change g in Progress g 

Ashley Jacobs, Pharm.D. 


Lutheran Health Network 

Fort Wayne, IN 


Disclosure: The speaker has no actual or potential conflict of interest in relation to this presentation. 

Which organ system is commonly associated 

with dabigatran side effects? 

– A: Respiratory system 

– B: Endocrine system 

– C: Excretory system 

– D: Digestive system 

A: Respiratory system 

0% 0% 0% 0% 

B: Endocrine system 

C: Excretory system 

http://www.vietvaluetravel.com/blog/2012/02/21/most‐asked‐questions‐about‐vietnam/ 

D: Digestive system 

8/29/2012 

4


Extended Stability of Intravenous 

Acetaminophen in Syringes and Opened 

Glass Bottles 

JJennifer if L. L Kwiatkowski, K i k ki Ph Pharm.D. D 

Pediatric Specialist at St. John’s Hospital, Springfield, IL 


Great Lakes Presentation from PGY2 Pediatric Pharmacy 

Residency at the University of Michigan 

The speaker has no actual or potential conflict of interest in relation to this presentation. 

Drug Development 

• Intravenous acetaminophen approved for use 

in Europe in 2001 

• Marketed in over 80 countries 

• Food and Drug Administration (FDA) approved 

in November 2010 

Jahr JS et al. Anesthesiol Clin. 2010;28(4):619‐45. 

Aqueous Decomposition 

Acetaminophen 

p‐aminophenol and acetic acid 

Koshy KT et al. J Pharm Sci. 1961;50:113‐8. 

Menezes HA et al. J Electroanal Chem. 2006; 586(1):39‐48. 

Hydrolysis 

Oxidation 

p‐benzoquinoneime 

Hydrolysis 

p‐benzoquinone 

Therapeutic Uses 

• Unable to tolerate oral or rectal drug 


• Potential reduction in opioid or NSAID related 

adverse effects 

• Insufficient response to IV opioids or NSAIDs 

• Contraindication to IV NSAIDs 

Babl FE et al. Pediatr Emerg Care. 2011;27(6):496‐9. 

Product Formulation 

• Limited water solubility 

– Higher at room temperature compared to 

refrigeration 

• Stability in aqueous solution 

Martindale 35th ed. 2007. 

Koshy KT et al. J Pharm Sci. 1961;50:113‐8. 

Influence of pH 

• Target pH 5‐6 

– Reported half life 19‐22 years 

• Acidic environment 

– Reported p half life

• Cysteine hydrochloride: antioxidant 

• Nitrogen gas in vial to reduce oxidation 

• Mannitol: isotonicity 

• No preservatives 

Excipients 

Ofirmev package insert. Cadence; 2010. 

Rowe RC et al. Handbook of pharmaceutical excipients. 5th ed. 2006. 

Schmitt E et al. EJHP 2003 6:96‐102. 

Audience Question 

Which of the following is a limitation of the current 6‐ 

hour usage guideline for intravenous acetaminophen? 

A. Potential for infusion related reactions due to administration 

guidelines 

B. Potential for dosing errors when dispensing the 1000 mg 

bottle of intravenous acetaminophen 

C. Potential for increased cost in adult patients receiving a 1000 

mg dose of intravenous acetaminophen 

D. Potential for product waste for pediatric patients who require 

only a portion of the 1000 mg bottle 

Beyond Use Dating 

• USP 797 guidelines for sterile compounding 

• Low‐risk level 

– Sterile for 48 hours at room temperature 

– AAseptic i manipulations i l i within ihi ISO Cl Class 5 air i 

quality or better 

– Institutional specifications for final dating 

USP Guidebook to Pharmaceutical Compounding— Sterile Preparations. 

Usage Guideline 

• Intravenous acetaminophen supplied as 1 

gram, 100 mL bottle with 6‐hour usage 

guideline 

Ofirmev package insert. Cadence; 2010. 

• Weight‐based dosing 

• Use of a fraction of the bottle 

• Product waste 

• Increased costs 

Pediatric Limitations 

• Disruption in pharmacy workflow 


Acetaminophen in Syringes and Opened Glass 

Bottles 

Jennifer Kwiatkowski, PharmD 

Cary Johnson, Pharm.D., FASHP 

Deb Wagner, Pharm.D., FASHP 

University of Michigan Hospitals and Health Centers 

8/29/2012 

2

Specific Aim 

• Specific aim 

– Determine if intravenous acetaminophen is stable over an 

84 hour time period over a range of doses stored in 

syringes and a range of volumes remaining in the original 

opened bottle 

• Hypothesis 

– Intravenous acetaminophen will maintain at least 90% of 

the original concentration over an 84 hour time period at 

room temperature 

• Stationary phase 

HPLC Components 

– C‐18 reverse phase column 

– 5‐µm µ p particle size ( (250 mm x 4.6 mm) ) 

• Mobile phase 

– Mixture of acetonitrile and deionized‐distilled 

water (20:80 v/v) containing 0.15% formic acid 

Acetaminophen. USP 34 NF 29. 

Acetaminophen Standard Curve 

• Analytical grade acetaminophen powder 

• 5‐point standard curve 

– 40, 45, 50, 55, 60 µg/mL 

• Standard was run after every 10 th assay sample 

as an external control 

High Performance Liquid Chromatography 

(HPLC) 

http://www.comsol.com/stories/waters_corp_hplc_systems/full 

Sample Detection 

• UV light detector 

– λ set at 243 nm 

• Flow rate 

– 1 mL/min 

• Samples 

– Diluted to 50 µg/mL expected concentration with 

mobile phase 

– Prepared in triplicate, each sample assayed in 

duplicate 

AJHP 2000;57:1150‐69. 

Audience Question 

According to ASHP guidelines for conducting a 

drug stability experiment, drug samples must be 

assayed how many times? 

AA. Once 

B. Twice 

C. Three times 

D. Four times 

8/29/2012 

3

Sample Preparation 

• Intravenous acetaminophen supplied as 10 mg/mL, 

100 mL bottle 

• Doses in syringes (triplicate) 

– 100 mg (10 mL in 10 mL syringe) 



• Volumes in original opened bottle (triplicate) 

– 250 mg (25 mL in bottle) 

– 900 mg (90 mL in bottle) 

Stability‐Indicating Assays 

• Forced decomposition of intravenous 

acetaminophen 

– 3% hydrogen peroxide 

– 1 N sodium hydroxide (pH 12) 

– 1 N hydrochloric acid (pH 2) 

• Procedure 

– Heat to 90ºC for 2 hours 

– Neutralized to pH 7 

Results 

y = 131692.3000x + 

1067843.7000 

R² = 0.9996 

• Visually inspected for color change and 

precipitate formation 

• pH measured 

Sample Analysis 

• Microbiological testing not performed 

Time 

Results 

Sample Acetaminophen Chromatogram 

Degradation 

Solution 

3% hydrogen 

peroxide 

1 N hydrochloric 

acid (pH 2) 

1 N sodium 

hydroxide (pH 12) 

HPLC Peak Height 

Results 

Degradation Peaks 

(minutes) 

Acetaminophen peak 

at 4.05 minutes 

Stability-Indicating Capability of HPLC Assay 

Acetaminophen peak: 4 minutes 

p‐aminophenol peak: 7.35 minutes 

Acetaminophen 

Degradation (%) 

246 2.46 5 

2.70, 6.08, 7.35 8 

2.64, 5.23, 7.35 25 

8/29/2012 

4

Stability of Intravenous Acetaminophen (10 mg/mL) at Room 

Temperature in Varying Storage Containers 

Sample Actual Initial 

Drug 

Concentrationa (mg/mL) 

100 mg 

(syringe) 

250 mg 

(syringe) 

500 mg 

(syringe) 

250 mg 

(bottle) 

900 mg 

(bottle) 

% Initial Concentration Remaining 

24 hours 48 hours 72 hours 84 hours 

9.94 ± 0.05 99.11 ± 0.52 100.54 ± 0.69 100.08 ± 0.38 100.02 ±0.53 

9.96 ± 0.02 99.66 ± 1.11 99.61 ± 0.68 99.83 ± 0.89 99.80 ±0.35 

9.96 ± 0.03 100.13 ± 0.37 99.83 ± 0.64 99.92 ± 058 99.68 ±0.55 

9.98 ± 0.03 99.67 ± 0.36 100.07 ± 1.26 99.37 ± 0.24 99.53 ±0.41 

9.93 ± 0.04 99.76 ± 0.33 100.03 ± 0.59 100.54 ± 0.58 100.31 ±1.22 

a Mean ±S.D. of duplicate determinants for three samples (n = 3). 

Conclusion 

• Intravenous acetaminophen (10 mg/mL) was 

physically and chemically stable in a range of volumes 

for up to 84 hours in the opened bottles and in 

polypropylene syringes 

References 

1. Babl FE, Theophilos T, Palmer GM. Is there a role for intravenous 

acetaminophen in pediatric emergency departments? Pediatr Emerg 

Care. 2011;27(6):496‐9. 

2. Jahr JS, Lee VK. Intravenous acetaminophen. Anesthesiol Clin. 

2010;28(4):619‐45. 

3. Martindale –The Complete Drug Reference. 35th ed. London: 

Pharmaceutical Press; 2007. 

4. Koshy KT, Lach JL. Stability of aqueous solutions of N‐acetyl‐p‐ 

aminophenol. J Pharm Sci. 1961;50:113‐8. 

5. Menezes HA, Maia G. Films formed by the electrooxidation of p‐ 

aminophenol (p‐APh) in aqueous medium: What do they look like? J 

Electroanal Chem. 2006; 586(1):39‐48. 

6. OFIRMEV (intravenous acetaminophen) package insert. San Diego, CA: 

Cadence Pharma; 2010 Nov. 

Results 

• No detectable change in sample color 

• No visible drug precipitation 

• No appreciable change in the initial pH (5.77 ±0.02) 

• Interday coefficient of variation: 1.8% 

• Intraday coefficient of variation: 1% 

Significance 

• Benefits of extending the stability of 

intravenous acetaminophen 

– Decreased product waste 

– Cost savings to patients and the healthcare system 

– Pharmacy workflow optimized by minimizing need 

for urgent dose preparation 

References 

7. Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipients. 

American Pharmacists Associations. 5th ed. London; Pharmaceutical 

Press; 2006. 

8. Schmitt E, Vainchtock A, Nicoloyannis N et al. Ready to use injectable 

paracetamol: easier, safer, lowering workload and costs. EJHP 2003 6:96‐ 

102. 

9. USP Guidebook to Pharmaceutical Compounding— Sterile 

Preparations. The United States Pharmacopeia, 34th revision, and The 

National Formulary, 29th ed. Rockville, MD: United States Pharmacopeial 

Convention; 2010:336‐73. 

10. ASHP guidelines on quality assurance for pharmacy‐prepared sterile 

products. American Society of Health System Pharmacists. Am J Health 

Syst Pharm. 2000;57(12):1150‐69. 

11. Acetaminophen. The United States Pharmacopeia, 34th revision, and The 

National Formulary, 29th ed. Rockville, MD: United States Pharmacopeial 

Convention; 2010:1720‐3. 

8/29/2012 

5

Questions? 



Acetaminophen in Syringes and Opened 

Glass Bottles 

Jennifer L. Kwiatkowski, Pharm.D. 

Pediatric Specialist at St. John’s Hospital, Springfield, IL 


Great Lakes Presentation from PGY2 Pediatric Pharmacy 

Residency at the University of Michigan 

8/29/2012 

32 

6

Interview: Getting ready to be 

interviewed for a PGY1 Residency 

Jill S. Borchert, PharmD, BCPS, FCCP 

Professor, Vice Chair and Residency Director 

Midwestern University Chicago College of 

Pharmacy 

The Interview: Purpose 

• Their Purpose: 

– Assess your qualifications 

– Assess your fit with their program and department 

• YYour PPurpose: 

– Assess whether their program fits with your 

interests and needs 

– Assess whether their department fits with you! 

The Interview: Format 

• Individual v. group 

– Often combination 

• Meeting with RPD, Director of Pharmacy 

M ti ith t 

• Meetings with preceptors 

• Meetings with residents 

• Tour 

• Lunch 

• Presentation or clinical case? 

8/29/2012 

1

The Interview: Your Preparation 

• Research the program!! 

• Ask about the expectations of the interview 

– Presentation? 

• Format, AV availability, audience, handout 

• Draw upon previously given presentations 

– Clinical case? 

• References, timing 

• Develop a list of questions you’ll ask 

• Think about answers to potential questions 

they’ll ask 

Questions They’ll Ask 

• Why do you want to do a residency? 

• Why THIS residency? 

• Goals (this year, 1 year, 5 years, 10 years) 

• Wh What t can YOU bring bi to t this thi program? ? 

• Strengths/weaknesses 

– Highlight how you have improved in areas of 

weakness 

• How do you manage ….time? ….stress?… 

conflict? 

Questions They’ll Ask 

• 3C’s 

– How do you handle change? 

– How do you handle criticism? 

How are you creative? 

– How are you creative? 

• Clinical scenarios/Behavioral 

– What would you do if…. 

– Tell me about an intervention 

– Give examples of…conflict resolution, group 

project, etc. 

8/29/2012 

2

Questions You Can Ask 

• Ask questions and ask appropriate questions 

– Nothing shows lack of interest like silence or 

questions not matched to the program 

• Typical day/rotation 

• How are projects selected? 

• How is the staffing component integrated? 

• Where are past residents now? 

• Consider asking preceptors/RPD and residents 

the same questions 

Miscellaneous 

• Be polite in all correspondence and with other 

co‐interviewees 

• Attire 

– Typical dress code 

– Comfortable shoes 

• Be prepared 

– Water 

– Money 

• Thank you notes 

8/29/2012 

3

PGY1 Residency Options 

Carol Heunisch, PharmD, BCPS 

WHY DO A RESIDENCY? 

• Opportunity to apply didactic knowledge 

• Work with interdisciplinary patient care team 

• Sharpen critical thinking skills 

• Learn about leadership characteristics 

• Exposure to variety of pharmacist career paths 

• Differentiate candidates through career 

• Networking 

RESIDENCY PROGRAM TYPES 

• Postgraduate Year 1 (PGY1) 

– Provide “generalist” training 

– Variety of practice settings: Health system, managed care, 

community. 

– Focus on development p of clinical judgment j g & problem‐ p 

solving skills. 

– Outcomes competencies: 

• Medication management 

• Leadership/practice management 

• Project management skills 

• Practice‐ and medication‐related education/training 

• Utilization of medical informatics 

– Pharmacy practice residency most common. 

8/29/2012 

1

RESIDENCY PROGRAM TYPES 

• Postgraduate Year 2 (PGY2) 

• Provide advanced training in focused area 

– Ambulatory care, Critical Care, Drug Information, 

Infectious diseases, practice management/administration, 

nuclear pharmacy—to name just a few! 

• Integrates PGY 1 experience to allow independent 

practitioner functioning. 

• Prepares for board certification in practice area. 

RESIDENCY PROGRAM BASICS 

– Almost 1000 PGY1 programs nationally‐hospital, 

clinic, community practice or managed care 

settings. 

– Approximately 2000 pharmacists do residencies 

annually. 

– Program length 1 year, full‐time commitment. 

– Paid stipend and usually benefits (insurance). 

– Areas of program focus/training: Administration, 

Infectious Disease, General Medicine, Critical 

Care, staffing, plus electives. 

RESIDENCY PROGRAM STATISTICS 

2012 

• Positions available: 

– PGY1: 2,408 (13% more 

than 2011). 

– PGY 1 applicants: 3706 

– PGY1 includes i l d general, l 

community, managed 

care positions. 

– PGY2: 590 (12% increase 

over 2011). 

• Actual matches: 

– PGY1: 2268 (13% more 

than filled in 2011). 

– PGY2: 505 (14% more 

than filled in 2011) 2011). 

• Includes 326 

positions filled in the 

match plus 179 early 

commits. 

8/29/2012 

2


• Program accreditation 

– ASHP accreditation means: 

• Training site compliant with standards of practice 

• Program committed to excellence in training 

• Continuous improvement of training and service 

• Peer‐reviewed, meets requirements of training 

• Recognition by potential employers 

• Accredited programs can be found at www.ashp.org in the 

“Residency Directory” 


• “The Match” 

– “Resident Matching Program” 

– A service that pairs residents with residency 

programs. 

– Residency candidates must sign up for Resident 

Matching Program. 

http://www.natmatch.com/ashprmp/ 

– Match results available in March. 

– NMS provides information about positions 

available after match completed. 

CONSIDERING A RESIDENCY? 

NOW WHAT? 

• Network and research prospective programs 

• 4th Professional year 

– Draft CV and cover letter 

– Letters of recommendation 

– Sign up with National Matching Service 

– Register for ASHP Midyear Clinical Meeting & participate in 

residency showcase & PPS (Personnel Placement Service) 

– Complete program applications—apply to several, don’t 

limit to one geographic area. 

– Interview 

– Submit ranking preferences to NMS 

– Match! 

8/29/2012 

3

ASHP MIDYEAR CLINICAL MEETING 

• Residency Showcase 

– Informal meetings with residents, program directors, and 

preceptors 

– Opportunity to ask questions and get program information 

– Programs listed by training site, not specific program type 

• ASHP Personnel Placement Service (PPS) 

– Optional, additional fee for participation 

– Opportunity to schedule one on one interviews 

– Good to narrow potential programs for on‐site interviews 

– Recruit for PGY1, PGY2 residents as well as fellowships 

– Search for “residency program postings” www.careerpharm.com 

PROFESSIONAL ORGANIZATION MEMBERSHIP 

• ICHP, ASHP, APhA 

• Offers network opportunities on and off campus 

• Access to programs like residency showcases at state 

and national meetings 

• Leadership opportunities 

• Access to journals such as AJHP for clinical & 

operational skills enhancement 

RESIDENCY RESOURCES 

• http://www.ashp.org 

• http://www.natmatch.com/ashprmp 

• http://www.careerpharm.com 

• http://www.ichpnet.org 

8/29/2012 

4

CV: The key to a top 

curriculum vitae 

Karen Kelly, Pharm.D. 

Pharmacy Manager 

Evanston Hospital 

NorthShore University HealthSystem 

What is a curriculum vitae (CV) 

• CV: Latin = course or outline of your life 

• Written profile of your professional 

qualifications 

• OOrganized i dli list of f achievements hi & experiences i 

• Focus on education, professional experience 

• Varies in length, one to several pages 

• Longer, more detailed than a resume 

• Living document 

What should be included in a CV? 

• Your contact information 

– Centered, top of page 

– Name, address, phone & email 

• Education 

– Most recent educational experience first 

– Spell out your degree, subject & school 

• Specialized Training & Certifications 

– CPR, ACLS, BCPS, immunization training 

– Include the full certification name and the year earned 

8/29/2012 

1


• Professional experience 

– Most recent experience first 

– Time employed, position title, name & location of 

employer, name & contact of supervisor 

– Description of position if not easily identifiable 

• Clerkship rotations 

– Good to list if right out of school 

– Spell out names; no abbreviations 


• Presentations 

– Include title, name of group presented to, year 

• Publications 

– Use official citation method 

• Honors & Awards 

– List title & year 

– Deans list – include quarter & year 


• Membership in organizations 

– include offices held 

• Licensure 

– include state & type yp of license 

• Professional & Community Service 

– Name of group, office held, scope of work 

• Other special experiences or skills 

– Any unique quality, language, training 

• References – list out 

8/29/2012 

2

Tips for a Top Notch CV 

• Focus on professional, pharmacy‐related 

information 

• Include positive information about your 

achievements 

• Use headings to identify each section 

• For offices held, describe the scope of 

responsibilities & their impact 

• Update regularly to reflect work experience, 

presentations 

Tips for a Top Notch CV 

• Identify your preceptors and supervisors by 

name, include their title 

• Use simple fonts –Times New Roman, Arial 

• High quality, quality conservative paper 

• Watch for spelling errors 

• Do not use abbreviations 

• Do no use colors 

• Be honest in the content 

• Have someone proofread it for you 

What do employers look for 

in a CV? 

• Signs of achievement 

• Willingness to work hard 

• Professionalism 

• Patterns of stability & career direction 

• Hard worker 

8/29/2012 

3

What NOT to Include in your CV 

• Personal information: age, marital status 

• Interests and hobbies 

• Reason for changing jobs or no job 

• Photo, unless requested 

• Information prior to pharmacy school except 

for education, previous degrees, or unique 

achievements 

– exclude high‐school 

CV: Conclusion 

• Be honest in your content 

• Highlight your strengths & achievements 

• Create a good first impression 

• Your CV as an advertisement for YOU! 

References 

• American Society of Health‐System Pharmacists. 

Accreditation, Resident Info, Curriculum Vitae. Available at: 

http://www.ashp.org/menu/Residents/GeneralInfo/Curriculu 

mVitae.aspx Accessed August 7, 2012. 

• CV‐Resume.org. CV Resume and Cover Letter. Available at 

http://cv‐resume.org. p// g Accessed August g 7, , 2012. 

• University of Kent Careers Advising Service. How to write a 

successful CV. Available at: 

http://www.kent.ac.uk/careers/cv.htm. Accessed August 7, 

2012. 

8/29/2012 

4

What is PhORCAS? 

• PhORCAS is the Pharmacy Online Residency Centralized 

Application Service, a web‐based residency application 

service 

• The goal of PhORCAS is to streamline the residency 

application process 

• PhORCAS is a partnership between ASHP Accreditation 

Services and Liaison International. Liaison International 

(www.liaison‐intl.com has built and maintains 22 other 

centralized application services (including PharmCAS) 

• PhORCAS will be divided into 3 main portals: the application 

portal, the program portal, and the reference portal. 

How is PhORCAS used by residency program 

applicants? 

• The residency applicant creates a PhORCAS account and is then transferred seamlessly to the 

National Matching Service (NMS) as part of the account creation process. 

– complete an application online in PhORCAS. 

– After the application is complete, applicants upload a personal statement/letter of intent and a copy of their 

curriculum vitae (CV). 

• They have the option of using the same personal statement and CV for all programs, or they can upload a unique personal 

statement and/or CV for select programs. 

– Applicants request one copy of their official transcripts that is mailed to PhORCAS where its authenticity is 

certified. The transcripts is then uploaded into the PhORCAS application portal. 

• PhORCAS provides a link to the ASHP online directory, allowing applicants to check for any 

additional site‐specific application requirements. 

• The applicant identifies three individuals who will be providing references. 

– The same individuals may be used for all sites, or the applicant may select a series of different individuals for 

select programs. 

– The applicant enters a contact email address for the reference 

• You may include a personal note for the automated message generated by PhORCAS alerting the reference of the request 

to provide a letter of recommendation. 

– The applicant will not be able to see the content of the submitted reference form or letter, but they will be 

able to track the completion of the reference provided to the program. 

How are PhORCAS and the National Matching 

Service (NMS) connected? 

• PhORCAS is linked with the National Matching Service (NMS), offering applicants the ability to 

register seamlessly with NMS as part of the PhORCAS application process. 

• Each program registered in the ASHP Resident Matching Program, with a unique NMS code, will 

automatically be uploaded into PhORCAS unless the program director selects an “Opt out” option. 

– The program name and application deadline date entered on the agreement will be uploaded into 

PhORCAS. 

• There will be routine updates p between NMS and PhORCAS to verify y that applicants pp have registered g 

for the match, or if new residency programs have been added to PhORCAS. 

• Following the match, NMS will produce a dynamic list of available programs post‐match thus 

allowing candidates to use PhORCAS in the post match (“scramble”) process. 

– The list of available programs offering positions post match will be posted in PhORCAS (if they participate in 

PhORCAS) to allow these individuals to apply to these programs electronically. 

– The information currently in PhORCAS can be used, or the applicant and reference writer can choose to 

customize to the new post match applications. 

– Applicants will submit their information from the PhORCAS application portal. Programs will see the new 

applications in a third section listed as the “Post match applications.” 

8/29/2012 

1

What are the benefits of PhORCAS to residency 

applicants? 

• One online submission 

– Applicants will not have to pay for multiple mailings and tracking of deliveries. 

– Information is transmitted real time to programs ‐ thus decreasing variations in mail deliveries. 

• Electronic tracking, notification of application process 

– ‐The applicant will know exactly what application components are pending and which reference writers have not 

submitted letters of reference at all times 

• Reduced applicant hassle with transcripts 

– Only one copy of each transcript is needed to be sent to the PhORCAS Transcripts Department for all participating 

programs 

• Flexibility to standardize or customize 

– Applicants can submit the same application materials to all programs or customize their application materials specific 

to each program they are applying (e.g. CV, personal statement). 

– PhORCAS allows uploads of supplemental information that may be required by a program, as long as it is in PDF (.pdf), 

MSWord (.doc), or Rich Text Format (.rtf), and/or ASDII Text File (.txt)). All programs specific application materials can 

be uploaded through the use of the Supplemental Information section in PhORCAS and can be specific just to that 

application. There is a space limitation of 5MB for supplemental data. 

• Consolidated National Matching Service (NMS) and PhORCAS registration 

– The applicant will enter the PhORCAS web site and is then transferred seamlessly to the NMS web site, allowing them 

to pay and register for NMS. 

System available for post‐match process 

– Applicants will be able to see residency programs accepting applications post‐match and can send their PhORCAS 

application materials to the appropriate residency programs. This reduces the mad dash or scramble to provide 

application materials to residency programs and eliminate expedited reference letter requests. 

FEES AND ADMINISTRATIVE INFORMATION 

• What is the fee for applicants? 

The initial applicant PhORCAS fee is $75 and includes the first 4 program selections. Each additional program 

selected is $25. 

PhORCAS will seamlessly transfer applicants to the National Matching Service (NMS) allowing them to pay and 

register for NMS. The NMS fee is $116. The applicant must be registered with NMS before applying to residency 

programs in PhORCAS. 

• How were the applicant fees for PhORCAS determined? 

Working with Liaison, ASHP compared comparable centralized application services, centralized application survey 

data from a survey ASHP conducted in 2011, and established a fee structure that was price conscious. 

ASHP conducted a survey of applicants completing the match process in 2011, and based the fee structure on 

these survey results. On average each candidate paid $145 and applied to 5 or 6 programs. Using PhORCAS 

applying to 6 sites will cost $125, keeping the fees below those identified in the survey. The fees for PhORCAS go 

to administering the service. 

• If an applicant is applying to a program with multiple sites, each with their own matching code, is the applicant 

applying to each site? 

Yes, the applicant applies to each individual site that has its own unique National Matching Service (NMS) code, 

however as all the sites are part of one residency (only one ASHP Residency number), the applicant will only have 

to pay for one residency application fee (the applicant can apply to all the sites associated with that residency 

program for one application fee: $25. 

8/29/2012 

2

Piecing together the new CHEST 

guidelines 

Highlights of CHEST 2012 

Erika Hellenbart, PharmD, BCPS 


The speakers have nothing to disclose. 

To what extent have you adopted 

the CHEST 2012 guidelines? 

1. All 

2. Most 

3. A few 

4. None 

0% 0% 0% 0% 

1 2 3 4 

Decrease in 1A recommendations 

• Thrombosis experts excluded from final 

recommendations1 – Involved in discussions and review of evidence 

– Unconflicted methodologists took responsibility 

for each chapter 

• Not necessarily thrombosis experts 

– Minimized financial and intellectual conflict of 

interest 

1. Guyatt GH, Akl EA, Crowther M, et al. Introduction to the ninth edition: antithrombotic therapy and prevention of thrombosis, 9 th 

ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2)(suppl): 48S-52S. 

Highlights of CHEST 2012 

• Downgraded strength of recommendations 

• Novel oral anticoagulants 

• Aspirin for everyone 

• Mechanical valve replacement and additional risk 

factors 

• Extended interval monitoring 

• Duration of anticoagulation therapy 

• Orthopedic prophylaxis 

• Perioperative bridging 

Defining recommendation grades 

Grade 1 Benefit vs. Risk Strength of Supporting 

Evidence 

1A Benefit clearly 

outweighs risk 

2A Benefits closely 

balanced with risks 

2B Benefits closely 

balanced with risks 

RCTs 

‐ consistent evidence 

‐ without important limitations 

Observational studies 

‐ Exceptionally strong 

RCTs 

‐ consistent evidence 

‐ without important limitations 

Observational studies 

‐ Exceptionally strong 

Limitations with RCTs 

Higher quality research may be 

required 

Implications 

Application to most 

patients in most 

circumstances 

Best action may differ 

depending on 

circumstances 

Best action may differ 

depending on 

circumstances 

1. Guyatt GH, Akl EA, Crowther M, et al. Introduction to the ninth edition: antithrombotic therapy and prevention of thrombosis, 9 th 

ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2)(suppl): 48S-52S. 

Decrease in 1A recommendations 

• New approach to determining strength of 

recommendation1 – 1A if treatment benefits all aspects of care 

– Surrogate vs. vs patient patient‐important important endpoints 

– Patient values and preferences considered2 • Accessibility 

• Financial impact 

1. Guyatt GH, Akl EA, Crowther M, et al. Introduction to the ninth edition: antithrombotic therapy and prevention of thrombosis, 

9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2)(suppl): 48S- 

52S. 

2. MacLean S, Mulla S, Akl EA, et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic 

review: antithrombotic therapy and prevention of thrombosis, 9 th ed: American College of Chest Physicians evidence-based 

clinical practice guidelines. Chest. 2012; 141(2)(suppl): e1S-e23S. 

9/4/2012 

1

Novel Oral Anticoagulants 

Dabigatran 3 Rivaroxaban 4 

FDA Indication Reduce risk of stroke or 

systemic embolism in non‐ 

valvular AF 

Reduce risk of stroke or 

systemic embolism in non‐ 

valvular AF 

Mechanism of Action Direct thrombin inhibitor 

DVT/PE prophylaxis 

following TKA or THA 

Factor Xa Inhibitor 

AF Dose 150 mg BID 20mg daily 

Renal Adjustment 75mg BID 

15mg daily 

(CrCl 15‐30 mL/min) (CrCl 15‐50 mL/min) 

Ortho Prophylaxis Dose N/A in US 10mg daily 

THA: 35 days 

TKA: 12 days 

3. Boehringer Ingelheim Pharmaceuticals, Inc. Pradaxa® (dabigatran etexilate) prescribing information. Ridgefield, CT; Boehringer Ingelheim Pharmaceuticals; 2012. Available at 

http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf. Accessed August 8, 2012. 

4. Janssen Pharmaceuticals, Inc. Xarelto® (rivaroxaban) prescribing information. Titusville, NJ; Janssen Pharmaceuticals; 2011. Available at 

http://www.janssenmedicalinformation.com/assets/pdf/products/files/Xarelto/pi/ENC-010330-11.pdf. Accessed August 8, 2012. 

• CHEST 2012 (9.5) 8 

Mechanical Valves 

– INR goal of 3.0 (2.5‐3.5) with mechanical valves in the 

mitral AND aortic position 

– No evidence of additional benefit with higher INR goal in 

patients with additional risk factors 

• Aortic valve with additional risk factors: INR goal of 2.5 

• CHEST 2008 (6.0.5) 9 

– INR goal of 3.0 (2.5‐3.5) with mechanical valve in 

EITHER/OR both the aortic or mitral positions, and 

additional risk factors for thromboembolism 

8. Whitlock RP, Sun JC, Fremes SE, et al. Antithrombotic and thrombolytic therapy for valvular disease: antithrombotic therapy and prevention of thrombosis, 9 th 

ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2)(suppl): e576S-e600S. 

9. Salem DN, O’Gara PT, Madias C, Pauker SG. Valvular and structural heart disease: antithrombotic therapy and prevention of thrombosis, 8 th ed: American 

College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2008; 133: 593S-629S 

Puzzle # 1: MJ 

• MJ is an 76 year old female patient who is presenting to your clinic upon 

discharge from the hospital with a diagnosis of atrial fibrillation 

• Vital signs at this visit 

– BP: 146/98 mmHg 

– HR 104 bpm 

– Ht 5’4, Wt 76 kg 

• ALL: enalapril (cough) (cough), terazosin (palpitations) (palpitations), sulfa (nausea) 

• PMH: 

– HTN 

• Labs: 

– Complete metabolic panel within normal limits; CrCl: 55ml/min 

– no other labs available at this time 

• Current Medications 

• metoprolol XL 25 mg at bedtime (started at discharge) 

• Iisinopril/HCTZ 20/12.5 mg in the morning 

• amiodarone 200mg daily (started at discharge) 

Aspirin for Primary Prevention 

• CHEST 2012 (2.1) 5,6 

– “For persons aged 50 years or older without 

symptomatic cardiovascular disease, we suggest 

low‐dose aspirin p 75 to 100mg g daily y over no aspirin p 

therapy” (2B) 

• CHEST 2008 (5.0‐5.4.1) 7 

– Moderate risk (10‐year risk > 10%) (2A) 

5. Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of 

thrombosis, 9 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012; 141(2)(suppl): e637S-e668S. 

6. Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from 

randomised trials. Lancet. 2011; 377: 31-41. 

7. Becker RC, Meade TW, Berger PB, et al. The primary and secondary prevention of coronary artery disease: antithrombotic therapy and prevention 

of thrombosis, 8 th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2008; 133: 776S-814S. 


guidelines 

Atriall Fibrillation b ll 

Part 1 

Shaunte Pohl PharmD, BCPS 

1. You JJ, Singer DE, Howard PA, et al. Antithrombotic Therapy for Atrial 

Fibrillation. CHEST 2012;141(2)(suppl): e531s‐e575s. 

2. Singer DE, Albers GW, Dalen JE, et al. Antithrombotic Therapy in Atrial 

Fibrillation. CHEST 2008;133:546S‐592S. 

3. Holbrook A, Schulman S, Witt DM, et al. Evidence‐based management 

of anticoagulant therapy: CHEST 2012;141(2)(suppl): e152s‐e184s. 

The 2012 CHEST guidelines would 

recommend which of the following for MJ? 

a. CHADS2 =0; start 

aspirin 

b. CHADS2= 1; start 

aspirin p and 

clopidogrel 

c. CHADS 2= 1; start 

oral anticoagulation 

d. CHADS 2 = 2; start 

oral anticoagulation 

A 

0% 0% 0% 0% 

B 

C 

D 

9/4/2012 

2

Initiating therapy 

CHEST 2012 2.1.8- 2.1.10 

CHADS2 Medication Recommendation 

Low Risk = 0 No therapy (2B) 

Intermediate Risk = 1 Oral anticoagulation (1B) 

High Risk = 2 or greater Oral anticoagulation (1A) 

The 2012 CHEST guidelines suggest which 

of the following medications for MJ? 

a. Warfarin 5 mg daily 

b. Aspirin 75 mg daily 

c. Dabigatran 150 mg 

twice i a day d 

d. Clopidogrel 75 mg 

daily 

A 

0% 0% 0% 0% 

Therapy recommendations 

CHEST 2008 1.1.2‐1.1.4 CHEST 2012 2.1.8‐2.1.11 

Low risk 

Long term aspirin therapy (1B) 

Intermediate risk 

Warfarin (1A) or aspirin (1B) therapy 

B 

C 

CHADS 2=0 

No medication therapy (2B) 

CHADS 2=1 

Dabigatran 150mg twice a day (2B) 

High risk 

CHADS CHADS2=2 =2 or greater 

Long term warfarin therapy (1A) Dabigatran 150mg twice a day (2B) 

Following patients are listed as exceptions to the above recommendation and 

adjusted dose VKA is recommended: 

• AF and mitral stenosis 

• AF and stable coronary artery disease 

• AF and placement of an intracoronary stent 

• AF and ACS with no intracoronary stent placement 

D 

Initiating therapy 

CHEST 2008 1.1.2‐1.1.4 CHEST 2012 2.1.8‐2.1.10 

Low risk 

Long term aspirin therapy (1B) 

CHADS 2=0 

No medication therapy (2B) 

Intermediate risk 

Warfarin (1A) or aspirin (1B) therapy 

CHADS CHADS2=1 =1 

Oral anticoagulation therapy (1B) 

High risk 

Long term warfarin therapy (1A) 

CHADS2=2 or greater 

Oral anticoagulation therapy (1A) 

Therapy recommendations 

• CHEST 2012 2.1.11 

– Recommends the use of dabigatran 150mg twice a 

day as first line oral anticoagulant therapy rather 

than dose adjusted j VKA therapy. py ( (2B) ) 

MJ requests that she be started on warfarin due to the 

cost of dabigatran. Her physician agrees and sends her 

to your clinic. The 2012 CHEST guidelines would 

suggest which of the following doses? 

a. Warfarin 2.5 mg for 

two days 

bb. Warfarin 5 mg for 

two days 

c. Warfarin 7.5 mg for 

two days 

d. Warfarin 10 mg for 

two days 

A 

0% 0% 0% 0% 

B 

C 

D 

9/4/2012 

3

Warfarin dosing 

CHEST 2008 2.1.1, 2.2.1 CHEST 2012 2.1 

Initial dose of 5‐10 mg for 1‐2 days (1B) Initial dose of 10 mg for 2 days (2C) 

Initial dose < 5 mg for (1C): 

No additional dosing recommendations 

Debilitated 

made 

Recent surgery 

Elderly 

Malnourished 

CHF 

Liver disease 

Taking medications that may increase 

sensitivity to warfarin 

Puzzle # 1: SB 

SB is a 92yo African American female with PMH of AF 

(diagnosed 2004), HTN, OA, PUD (ulcer 1960), CKD 

(CrCl~20ml/min) and history of breast cancer. 

Current medications: warfarin 5mg (7.5mg Sun and 5mg 

rest of week) aspirin 81mg daily, furosemide 40 daily, 

esomeprozole 40mg daily, docusate 100mg daily prn, 

diltiazem 180 daily, calcium carbonate 500mg daily, 

vitamin D 1000units daily, metoprolol 50mg twice 

daily, anastrazole 40mg daily 

A pharmacy student asks you if this patient is a candidate for 

“extended duration” follow‐up, per the new CHEST guidelines. 

Your response: 

A. No, because of her age 

B. No, because she had one 

out of range INR in the last 

6 months 

CC. No No, because she is 

noncompliant with visits 

D. Yes, she is a candidate 

0% 0% 0% 0% 

A. B. C. D. 


guidelines 

Atrial Fibrillation (AF) 

PPart 2 

Brooke Griffin, PharmD 

Recent INR values (goal INR 2‐3) 

Date INR Recommendation 

8/27 2.4 Continue present management (CPM) 

(7.5mg Sun and 5mg rest of week) 

7/30 2.2 CPM 

7/2 2.4 CPM 

6/5 / 

2.2 CPM 

5/28 2.1 CPM 

5/7 2.7 CPM 

4/16 1.9 CPM 

4/2 2.3 CPM 

What is “Extended Duration?” 

CHEST 2012 (3.1) 1 

• “For patients taking VKA therapy with consistently 

stable INRs, we suggest an INR testing frequency of 

up to 12 weeks rather than every 4 weeks” (2B) 

CHEST 2008 (2.3.2) 2 

• “For patients taking a stable dose of oral 

anticoagulants, we suggest monitoring at an interval 

of no longer than every 4 weeks” (2C) 

. 

1. Holbrook A, Schulman S, Witt DM; et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th 

ed: American College of Chest Physicians evidence-based clinical practice guidelines, Chest 2012 1412suppl e152S-e184S 

2. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin k antagonists. CHEST. June 

2008;133(6_suppl):160S-198S. doi: 10.1378/chest.08-0670 

9/4/2012 

4

What is “Consistently Stable?” 

One reference in CHEST 2012 1 

• One year, single center study 2 (n=250, age ~70, mostly men, mostly AF) 

– Patients were on the same dose x 6 months 

– Patients were interviewed every 4 weeks 

– Results: 12 week follow‐up is safe and noninferior to 4 week 

ffollow‐up ll 

– No clinical outcomes 


• Grade 2B recommendation 

• May be useful in well educated, stable, compliant, young patients 

1. Holbrook A, Schulman S, Witt DM; et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th 

ed: American College of Chest Physicians evidence-based clinical practice guidelines, Chest 2012 1412suppl e152S-e184S 

2. Schulman S, Parpia S, Stewart C, et al. Warfarin Dose Assessment Every 4 Weeks Versus Every 12 Weeks in Patients With Stable International Normalized 

Ratios. Ann Intern Med 2011; 155: 653-59 

Does SB need Vitamin K? 

CHEST 2012 (9.1) 1 

• “For patients taking VKAs with INRs between 4.5 and 

10 with no evidence of bleeding, we suggest against 

the routine use of vitamin K” (2B) 

• • “For For patients taking VKAs with INRs ≥10.0 ≥10 0 and with 

no evidence of bleeding, we suggest that oral vitamin 

K be administered” (2C) 

– There was no difference in thromboembolic events or 

bleeding episodes when vitamin K was administered 

compared to placebo (pooled analysis). 2‐5 

1.Holbrook A, Schulman S, Witt DM; et al. Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: 

American College of Chest Physicians evidence-based clinical practice guidelines, Chest 2012 1412suppl e152S-e184S2. 

2.Crowther MA , et al . Ann Intern Med .2009 ; 150 ( 5 ): 293 - 300 

3. Crowther MA , et al . Lancet . 2000; 356( 9241): 1551- 1553 

4. Ageno W, et al . Thromb Haemost . 2002 ; 88 ( 1 ):48 - 51 

5. Ageno W, Garcia D, Silingardi M, Galli M, Crowther, M .. J Am Coll Cardiol . 2005 ; 46 ( 4 ): 730 - 742 

Can SB switch to dabigatran? 

CHEST 2012 (2.1.11) 

• “For patients with AF, including those with 

paroxysmal AF, for recommendations in favor 

of oral anticoagulation, anticoagulation we suggest dabigatran 

150mg twice daily rather than adjusted‐dose 

VKA therapy (target INR range, 2‐3)” (2B) 

You JJ, Singer DE, Howard PA; et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: American 

College of Chest Physicians evidence-based clinical practice guidelines, Chest 2012 1412suppl e531S-e575S 

SB comes to your anticoagulation clinic today and her INR is 9.4 

for an unknown reason. She denies bleeding. Her current dose 

of warfarin is 7.5mg Sunday and 5mg all other days. 

What is your recommendation before her return visit? 

A. Vitamin K 2.5mg PO x 1 

dose 

B. Vitamin K 5mg PO x 1 

dose 

C. Hold 1 dose of warfarin 

D. Hold 2 doses of warfarin 

E. Send to ER 

0% 0% 0% 0% 0% 

A. B. C. D. E. 

SB asks you about a new drug she heard about on the 

news for AF, dabigatran. What is your response? 

A. Dabigatran is not 

approved for AF 

B. CHEST 2012 

recommends warfarin 

over dabigatran for AF 

C. SB is not a candidate 

D. SB is a candidate 

0% 0% 0% 0% 

A. B. C. D. 

Details about dabigatran 

CHEST 2012 1 

• Dabigatran is favored in patients with AF who 

are similar to patients in the RE‐LY trial 2 

– No valvular disease, younger patients, no liver disease, not 

pregnant, CrCl l >30ml/min l/ 2 

• Dabigatran is the only new FDA‐approved 

VKA therapy alternative for AF 

1. You JJ, Singer DE, Howard PA; et al. Antithrombotic therapy for atrial fibrillation: antithrombotic therapy and prevention of thrombosis, 9th ed: 

American College of Chest Physicians evidence-based clinical practice guidelines, Chest 2012 1412suppl e531S-e575S 

2. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2010;361:1139-151 

9/4/2012 

5

Dabigatran vs. Rivaroxaban for AF? 

Dabigatran Rivaroxaban 

Main Trial RE‐LY1 ROCKET‐AF2 Patients in 

Trial 

Efficacy 

Compared to 

Warfarin 

•N=18,000; mean age 71; male 65% 

•CHADS‐2 score ≥3 (33%) 

•110mg twice daily: Non‐inferior 

(not approved) 

•150mg twice daily: Superior 

Renal Dosing CrCl 15‐30ml/min: 75mg twice 

daily, however, pts with 

CrCl

Puzzle # 2A: patient has just completed 6 

months of warfarin therapy after an unprovoked 

distal deep vein thrombosis. What is your long 

term anticoagulation recommendation? 

1. D/c all anticoagulants 

2. Continue warfarin 

3. Switch to aspirin 

4. Switch to dabigatran 

5. Order other diagnostic 

tests 

6. Other 

0% 0% 0% 0% 0% 0% 

1 2 3 4 5 6 

Making the case for halting 

anticoagulants or continuing warfarin 

• CHEST 2012 (3.1.4) 

– “In patients with unprovoked DVT of leg (distal or 

proximal), we recommend… at least 3 months over 

treatment of shorter duration. After 3 months …should be 

evaluated l t df for th the risk‐benefit ikb fitratio ti of f extended t d dth therapy” ” 

(1B) 

• CHEST 2012 (3.4) 

– “In patients with DVT of leg who receive extended therapy, 

we suggest treatment with the same anticoagulant chosen 

for the first 3 months” (2C) 

Making the case for transition to 

dabigatran 

• CHEST 2012 (remarks on section 3.3) 

– “Treatment of VTE with dabigatran or rivaroxaban, in 

addition to being less burdensome…may prove to be 

associated with better clinical outcomes” 

– PPostmarketing t k ti studies t di not t available il bl at t time ti of f guideline id li 

preparation 

• RE‐MEDY : dabigatran = warfarin in 6‐36 month 

extension but ↑ MI rate with dabigatran 

• RE‐SONATE: dabigatran > placebo in 6 month 

extension, no difference in MI rate 

• Both studies were presented as abstracts at International Society on Thrombosis and Haemostasis July 2011 

2012 vs 2008: different answers? 

• CHEST 2008 

– More generalized 


2.1.1 provoked (transient risk 

factor) 

2.1.2 unprovoked 

2.1.3 concurrent malignancy 

1. Kearon C, Kahn S, Agnelli G, et al. Antithrombotic therapy for venous 

thromboembolic disease. CHEST 2008; 133: 454S‐545S. 

• CHEST 2012 

– Much more specific for 

patient subgroups 

3.1.1: provoked proximal (surgery) 

3.1.2: provoked proximal (transient 

risk factor) 

3.1.3: any provoked distal 

3.1.4(.1‐5): unprovoked (various) 

3.1.5: concurrent malignancy 

Making the case for transition to 

aspirin 

• CHEST 2012: no mention of aspirin as an 

option in this context 

• WARFASA study (2012) 

– RCT of f 402 unprovoked kdVTE VTE patients ti t after ft 6‐18 6 18 

months of VKA therapy 

– ASA 100mg daily vs placebo 

– ASA decreased DVT rate but no difference in PE 

1. Becattini, et al. Aspirin for preventing recurrence of venous thromboembolism. N Engl J Med 2012; 366 (21): 1959‐67. 

Making the case for re‐evaluating 

objective testing 

• D‐Dimer – systematic review of 1 st unprovoked VTE 

• Negative result ~ 3.5% annual recurrence rate 

• Positive result ~ 8.9% annual recurrence rate 

• Verhovsek, et al. Ann Intern Med 2008; 149: 481‐490. 

• Venous doppler – mixed opinion 

pp p 

• Prandoni, et al: (+) residual thrombus = ↑ risk 

• PROLONG: (+) residual thrombus = not a risk factor 

• Prandoni, et al. Ann Intern Med 2002; 137: 955‐960. 

• Cosmi, et al. Eur J Vasc Endovasc Surg 2010; 39: 356‐365. 

• Thrombophilia screening 

• No evidence to support benefit of testing routinely 

• CHEST guidelines: do not address topic for 

duration of therapy 

9/4/2012 

7

Other Key Updates Related to VTE 

• Medical Prophylaxis 

– Acutely ill hospitalized medical pa�ents at ↑ VTE risk 

• LMWH, UFH, or fondaparinux (grade 1B) 

– Acutely ill hospitalized medical pa�ents at ↓ VTE risk 

• Do Do not use use pharmacologic or mechanical prophylaxis (grade 1B) 

• Suspected VTE 

– High suspicion –use parenteral anticoagulant 

– Intermediate –use parenteral anticoagulant if results 

delayed > 4 hours 

– Low suspicion –no anticoagulant recommended (if results 

within 24 hours) 

Puzzle #1‐ The random 1.5 INR 

• JJ is a 58 year old WF who presents to the anticoagulation clinic for routine 

INR check. She has been on warfarin since her (mechanical) mitral valve 

replacement surgery in 2008. Her current warfarin dose is 5 mg daily. 

– No c/o bleeding or bruising. JJ typically eats a spinach salad 3x/week 

and is typically very consistent with greens. No recent medication 

changes changes, OTC meds, meds or herbals. herbals 

– She missed a dose four days ago. 

– Other medications: lisinopril 10 mg daily, pravastatin 20 mg daily 

• INR today is 1.5 

• This is the lowest INR reported to date. JJ’s INR has been very stable in the 

past year in the 2.5‐3.5 range. Four weeks ago, her INR was 3.3. 

CHEST 2012 Recommendations 

• CHEST 2012 (3.2): 

– “For patients taking VKAs with previously stable 

therapeutic INRs who present with a single out‐of‐range 

INR of 0.5 below or above therapeutic, we suggest 

continuing the current dose and testing the INR within 11‐2 2 

weeks” (2C) 

• CHEST 2012 (3.3): 

– “For patients with stable therapeutic INRs presenting with 

a single subtherapeutic INR value, we suggest against 

routinely administering bridging with heparin” (2C) . 


Guidelines 

Bridging Recommendations 

Kathleen Vest, PharmD, CDE 

1. Douketis JD, Spyropoulos AC, Spencer FA, et. Al. Perioperative 

Management of Antithrombotic Therapy: Antithrombotic Therapy and 

Prevention of Thrombosis. CHEST 2012; 141; e326S‐e350S. 

2. Douketis JD, Berger PB, Dunn AS. The Perioperative Management of 

Antithrombotic Therapy: CHEST 2008; 133; 299‐339. 

What would you recommend for 

this patient? 

A. 10 mg x 1, then CPM. 

Recheck 5d 

B. 10 mg x 1, then CPM. 

Start LMWH until INR ≥ 

2.5. Recheck 3d 

C. Increase to 7.5 mg 

Sat/Tue; 5 mg other 

days. Recheck 10d 

D. CPM. Recheck one week 

0% 0% 0% 0% 

1 2 3 4 

Puzzle #2: Warfarin therapy interruption 

• It is a few months later. You received a phone call today from 

JJ. She has been “back on track” for awhile, but now is 

inquiring about her upcoming colonoscopy. It is scheduled for 

October 1st at 9:00 AM. 

– She had a colonoscopy in 2006 and polyps were removed removed. 

The gastroenterologist wants her to hold warfarin prior to 

procedure. 

– She is wondering what she needs to do. 

• Recent labs (done last month): CBC‐ WNL, CrCl=68 ml/min, 

current weight= 176 lb. 

– Last INR was 3.1 two weeks ago. 

9/4/2012 

8

What would you do for JJ? 

• A. Hold warfarin 9/26 ‐9/30. Bridge with enoxaparin 

80 mg q12 hrs. 

• B. Hold warfarin from 9/26‐9/30. Bridge with 

enoxaparin 80 mg daily. 

• C. Hold warfarin from 9/28‐9/30. Do not bridge. 

• D. Cancel colonoscopy. 

Risk 

Stratum 

Risk Stratification for Determining 

the Need for Bridge Therapy 

Mechanical Heart Valve Atrial Fibrillation VTE 

High •Any mitral valve prosthesis 

•Any caged‐ball or tilting disc 

aortic valve prosthesis 

•Recent (within 6 months) stroke 

or TIA 

Medium Bileaflet aortic valve prosthesis 

and 1 or more of the following 

RFs: 

•Afib, prior stroke or TIA, HTN, 

DM, CJF, age >75 y/o) 

Low Bileaflet aortic valve prosthesis 

without Afib and no other risk 

factors for stroke 

•CHADS2 score 5 or 6 

•Recent (within 3 months) 

stroke or TIA 

•Rheumatic valvular heart 

disease 

•Recent (within 3 months) VTE 

•Severe thrombophilia (Protein C, S, 

antithrombin def.); antiphospholipid 

antibodies 

CHADS2 score of 3 or 4 •VTE within the past 3‐ 12 months 

•Nonsevere thrombophilia (ex. 

Heterozygous Factor V leiden, 

prothrombin gene mutation) 

•Recurrent VTE 

•Active cancer (treated within 6 

months or palliative 

CHADS2 score of 0‐2 

(assuming no prior CVA or 

TIA) 

CHEST Guidance 

VTE >12 months previous and no other 

risk factors 

• CHEST 2012 (2.1): 

– “In patients who require temporary interruption of a VKA before surgery, 

we recommend stopping VKAs approximately 5 days prior to surgery 

instead of stopping VKAs a shorter time before surgery” (1C) 

• CHEST 2012 (2.4): 

– “In patients p with a mechanical heart valve, , Afib, , or VTE at high g risk for 

thromboembolism, we suggest bridging anticoagulation instead of no 

bridging during interruption of VKA therapy” (2C) 

• CHEST 2012 (2.2): 

– “In patients who require temporary interruption of a VKA before surgery, 

we recommend resuming VKAs approximately 12 to 24 h after surgery 

(evening or next morning) and when there is adequate hemostasis instead 

of later resumption of VKAs” (2C) 

What would you do for JJ? 

A. Hold warfarin 9/26‐ 

9/30. Bridge with 

enoxaparin 80 mg q12 

hrs. 

BB. Hold warfarin from 

9/26‐9/30. Bridge with 

enoxaparin 80 mg daily. 

C. Hold warfarin from 

9/28‐9/30. Do not 

bridge. 

D. Cancel colonoscopy. 

0% 0% 0% 0% 

1 2 3 4 

Surgeries/procedures associated 

with increased bleeding risk 

• Urologic surgery and procedures (transurethral prostate 

resection (TURP), bladder resection, nephrectomy, kidney 

biopsy 

• Pacemaker or implantable cardioverter defibrillator device 

implantation 

• Colonic polyp resection 

• Surgery in vascular organs (ex. kidney, liver, spleen) 

• Bowel resection 

• Major surgery with extensive tissue injury (cancer surgery, 

joint arthroplasty, reconstructive plastic surgery) 

• Cardiac, intracranial, or spinal surgery 

CHEST Guidance 

• CHEST 2012 (4.4): 

– “In patients who are receiving bridging anticoagulation 

with therapeutic‐dose SC LMWH and are undergoing non‐ 

high bleeding‐risk surgery, we suggest resuming 

therapeutic‐dose therapeutic dose LMWH approximately 24 h after surgery 

instead of resuming LMWH more than 24 h after surgery” 

– “In patients who are receiving bridging anticoagulation 

with therapeutic‐dose SC LMWH and are undergoing high 

bleeding‐risk surgery we suggest resuming therapeutic‐ 

dose LMWH 48‐72 after surgery instead of resuming 

LMWH within 24 h after surgery” (2C) 

9/4/2012 

9

Key Pearls with Bridging 

• See patients at least one week prior to the scheduled 

surgery date to plan appropriately 

– Balance risks of VTE vs. perioperative bleeding 

– Communicate with patient and involved providers 

– Factor in other issues such as cost/insurance 

coverage, ability to inject 

• Make sure you have updated labs and weight (CrCl 

and CBC) 

Date Enoxaparin dose/frequency Warfarin dose 

SB‐ to bridge or not to bridge? 

• Bridge and hold warfarin x 5‐7 days prior 

• Not bridge and hold warfarin x 5‐7 days prior 

Key Pearls with Bridging 

• Provide patients and providers with a calendar 

• Patient and caregiver education on injection 

technique and calendar 

• If possible possible, check INR on the date before surgery 

• Assess post‐op bleeding to help determine restart of 

anticoagulant medications 

• Close follow up of INR following procedure/surgery 

Remember SB? 

• SB is a 92 y/o African American female with 

PMH of AF (diagnosed 2004), HTN, OA, PUD 

(ulcer 1960) and history of breast cancer. 

• SB will be undergoing a spinal epidural in two 

weeks and is wondering what to do. 

• She tells you that one of her friends had to 

take some sort of shots when off of warfarin 

and she is wondering if she needs to do this 

too? 

SB ‐ to bridge or not to bridge? 

A. Bridge and hold 

warfarin x 5‐7 days 

prior 

BB. Do not bridge and 

hold warfarin x 5‐7 

days prior 

0% 

0% 

1 2 

9/4/2012 

10

Considerations for SB 

• Bleeding risk 

– Age 

– Spinal procedure‐ risk of bleeding is high 

• Thrombosis risk 

– CHADS2 score of 2: HTN and age >75 y/o 

• Low risk‐ do not bridge. 

– Lots of discussion needed in these scenarios between 

patient, anticoagulation provider, PCP and other physicians 

involved! 


guidelines g 

Erika Hellenbart, PharmD, BCPS 

Shaunte Pohl, PharmD, BCPS 

Brooke Griffin, PharmD 

Brian Cryder, PharmD, BCACP, CACP 

Kathleen Vest, PharmD, CDE 

2. GM is a 66yo male who has atrial fibrillation and 

renal insufficiency (CrCl 25ml/min) He brings a 

prescription to your pharmacy for 

rivaroxaban. Which of the following is a true 

statement? 

a. GM should not use rivaroxaban because it is 

contraindicated in patients with CrCl

4. The standard dose of dabigatran for the risk 

reduction of stroke in patients with non‐ 

valvular atrial fibrillation is: 

a. 150mg BID 

bb. 110mg BID 

c. 50mg BID 

d. 40mg BID 

6. JP is a 60 year old male patient who has been treated with 

warfarin for the past 6 months following an unprovoked deep 

vein thrombosis of the right lower extremity. His primary care 

physician would like to halt warfarin therapy and initiate 

aspirin 325mg daily. Does CHEST 2012 support this decision? 

a. Yes ‐ it is included as a 1B recommendation for all 

unprovoked p DVT patients p 

b. Yes ‐ it is included as an alternative for patients who are not 

candidates for transition to dabigatran 

c. No ‐ CHEST 2012 states that aspirin use has no benefit 

following warfarin treatment for DVT prevention 

d. No ‐ CHEST 2012 does not recommend for or against aspirin 

use after warfarin, but one clinical study supports this option 

8. Which of the following patients would be 

considered high risk for VTE? 

a. 39 year old male with AFib, HTN and diabetes. 

b. 79 year old female with HTN, diabetes, AFib, 

and a history of TIAs. 

c. 45 year old patient with a history of PE five 

months ago. 

d. 76 year old male with a history of an aortic 

valve replacement and diabetes. 

5. Per CHEST 2012, which of the following drug classes 

is preferred for use in total knee arthroscopy 

thromboprophylaxis in the absence of 

contraindications? 

a. Direct thrombin inhibitors (e.g. dabigatran) 

b. Low molecular weight heparin (e.g. enoxaparin) 

c. Vitamin K antagonist (e.g. warfarin) 

d. Factor Xa inhibitor (e.g. rivaroxaban) 

7. SG is a 47 year old patient with a mechanical 

heart valve in the aortic position. This patient 

does not have any other cardiovascular risk 

factors. According to CHEST 2012, what is the 

recommended INR goal? 

a. 1832 1.8‐3.2 

b. 2.0‐3.0 

c. 2.5‐3.5 

d. 3.0‐4.0 

9. Which of the following procedures is 

associated with a high bleeding risk according 

to CHEST 2012? 

a. Root canal 

b. Transurethral prostate resection (TURP) 

c. Cataract surgery 

d. Dermatologic surgery 

9/4/2012 

12

Presentation Outline ICHP Annual Meeting September 13-15

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