Proton Pump Inhibitors - CME Conferences

6 th Annual Primary Care Spring Conference Thursday, April 12, 2012 

Using Evidence-Based and Cost 

Effective Drug Therapy: Where do 

Generic Medications Fit? 

C. Wayne Weart Pharm. D., BCPS, FASHP, 

FAPhA 

Professor of Clinical Pharmacy and Outcome 

Sciences 

Professor of Family Medicine 

MUSC Campus SC College of Pharmacy 

1 

Faculty Disclosure 

• I am on the speakers bureau for Pfizer in the 

area of lipids and pain 

• I am a consultant for Merck in the area of 

outcomes research 

Wayne Weart, Pharm D 

Cost Effective Rx


Cost Consciousness in Patient Care — What Is 

Medical 

Education’s Responsibility? 

Molly Cooke, M.D. 

• “Value can be increased through costconscious 

diagnostic and management 

strategies and by the engineering of better 

and less wasteful processes of care. 

Evidence-based medicine and comparativeeffectiveness 

research help us understand 

the relative effectiveness of management 

strategies; appreciation of cost and metrics 

such as “number needed to treat” help us 

approach value.” 

– NEJM 2010, 362;14:1253 

3 

How Many Prescriptions Go Unfilled? 

• Oct. 26, 2011 Twenty four percent of patients 

given a new medication by their doctor did 

not fill the prescription in 2008, according to a 

new study by researchers at Harvard 

University, Brigham and Women's Hospital 

and CVS Caremark and published in the 

American Journal of Medicine (2011) 124, 

1081.e9-1081.e22 

4 


Cost Effective Rx


AARP Rx Watchdog Report 

• Rx Price Watch Report August 2010 

– Trends in Retail Prices of Brand 

Name Prescription Drugs Widely 

Used by Medicare Beneficiaries 2005 

to 2009 

• By Stephen W. Schondelmeyer PRIME Institute, 

University of Minnesota 

• Leigh Purvis AARP Public Policy Institute 

5 

Average Annual % Change in Retail 

Prices for Widely Used Brand Name 

Prescription Medications 

AARP Rx Price Watch Report 8-2010 http://www.aarp.org/ppi 

6 


Cost Effective Rx


Average Annual % Change in Retail 

Prices for Widely Used Brand Name 

Prescription Medications 

AARP Rx Price Watch Report 8-2010 http://www.aarp.org/ppi 

7 

Generic Medication Use 

• In 2010 ~78% of all medications dispensed in 

the US were for generic medications 

• Recent Harris Poll (1/26/09) 

– Found that between Oct 2006 and Dec 2008 the 

proportion of adults who would choose generic 

drugs over branded drugs increased from 68% to 

81% 


Cost Effective Rx


2010 Top 200 Generic Drugs by 

Total Prescriptions 

Rank Drug Total Rxs % Change from 2009 

• 1 Hydrocodone/APAP 122,806,850 2.1% 

• 2 Lisinopril 76,901,813 4.3% 

• 3 Simvastatin 76,771,821 4.9% 

• 4 Levothyroxine 68,222,152 8.2% 

• 5 Amoxicillin 51,083,822 -0.6% 

• 6 Amlodipine besylate 50,186,652 11.7% 

• 7 Azithromycin 48,756,188 -2.1% 

• 8 Alprazolam 46,201,182 3.9% 

• 9 Hydrochlorothiazide 45,838,017 -0.8% 

• 10 Omeprazole 44,795,175 15.4% 

– Drug Topics 2011 www.drugtopics.com 

2010 Top 200 Generic Drugs by 

Total Prescriptions 

Rank Drug Total Rxs % Change from 2009 

11 Metformin 41,932,689 4.7% 

• 12 Furosemide oral 36,583,895 -0.1% 

• 13 Metoprolol tartrate 34,707,807 -0.5% 

• 14 Atenolol 33,839,806 -11.0% 

• 15 Sertraline 33,409,838 8.9% 

• 16 Metoprolol succinate 32,224,000 12.0% 

• 17 Zolpidem tartrate 29,719,569 -2.8% 

• 18 Oxycodone/APAP 28,705,243 6.8% 

• 19 Citalopram HBR 27,993,635 9.4% 

• 20 Gabapentin 26,865,557 14.0% 

– Drug Topics 2011 www.drugtopics.com 

10 


Cost Effective Rx


April 20, 2011 —A report from the IMS Institute 

for Healthcare Informatics 

• Continuing a major trend, IMS finds that 78% 

of the nearly 4 billion U.S. prescriptions 

written in 2010 were for generic drugs. 

• Commercial insurance helped pay for 63% of 

prescriptions, down from 66% five years ago. 

• Federal government spending through 

Medicare Part D covered 22% of prescriptions. 

Medicare Closing of the “Doughnut Hole” 

13 


Cost Effective Rx


Medicare Closing of the “Doughnut Hole” 

14 

Prescription Drug Prices Under Negotiation In 

Debt Talks. 

• 6/21/2011 a bipartisan bill HR2248 by Peter Welch D-Vt and 

Jo Ann Emerson R-Mo "requiring the government to negotiate 

lower prescription drug prices in Medicare" has been 

reintroduced. Supporters say this will save up to $156 billion 

over 10 years without cutting into benefits. The 

Pharmaceutical Research and Manufacturers of America, 

representing drug companies, said Medicare already has drug 

discounts. Currently HHS is not allowed to negotiate drug 

costs with manufacturers; the proposed bill would require 

negotiation. House Democrats have supported similar 

measures, saying the current program results in beneficiaries 

paying "higher prices than they should for prescription drugs.“ 

– S44 is the companion bill in the Senate 


Cost Effective Rx




• For Americans covered by insurance, 

Medicare, or Medicaid, the average copayment 

for a prescription was $10.73 -- down 

a bit from 2009 due to increased use of generic 

drugs. 

• The average co-payment for branded drugs for 

which generic alternatives were available 

jumped 6% to $22.73. 

In 2010 the 10 drugs on which we 

spent the most were: 

1. Lipitor (atorvastatin)-- $7.2 billion (11-2011) 

2. Nexium (esomeprazole)-- $6.3 billion 

3. Plavix (clopidogrel) -- $6.1 billion (5-2012) 

4. Advair Diskus (salmeterol/fluticazone)-- $4.7 billion 

5. Abilify (aripiprazole)-- $4.6 billion 

6. Seroquel (quetiapine)-- $4.4 billion (3-2012) 

7. Singulair (montelukast)-- $4.1 billion (8-2012) 

8. Crestor (rosuvastatin)-- $3.8 billion 

9. Actos (pioglitazone)-- $3.5 billion (8-2012) 

10. Epogen (epoetin alfa)-- $3.3 billion 

2010 IMS report: 


Cost Effective Rx


Additional Opportunities for Generic 

Savings in 2011-2012 

• Levofloxacin – Levaquin 6-2011 

• Olanzapine – Zyprexa 10-2011 

• Atorvastatin/amlodipine – Caduet 11-2011 

• Escitalopram – Lexapro 2-2012 

• Ibandronate – Boniva 3-2012 

• Sildenafil – Viagra 3-2012 

• Irbesartan – Avapro 3-2012 

• Entanercept – Enbrel 8-2012 

• Valsartan – Diovan 9-2012 

• Valsartan/amlodipine – Exforge 9-2012 

• Ziprasidone – Geodon 9-2012 

• Candesartan – Atacand – 12-2012 

• Rizatriptan – Maxalt 12-2012 

April 20, 2011 —A report from the IMS 

Institute for Healthcare Informatics 

• The IMS reports that Americans spent $307 

billion on prescription drugs in 2010 

• Brands that lost their protection from generic 

competition led to $12.6 billion less spending in 

2010 than in 2009. 

• The price increase for drugs without generic 

competition led to $16.6 billion more spending in 

2010 than in 2009. 

• Drug companies offered $4.5 billion in rebates to 

assist patients with the high cost of brand name 

drugs for which there was no generic alternative. 

2010 IMS report: 


Cost Effective Rx




• Small molecule spending totaled $240 

billion,an increase of 0.5% as biologics grew 

by 6.6%, amounting to $67 billion. 

• Oral forms of medicines declined by 0.1%, but 

spending on injectables increased by 5.7%. 

FDA 

Regulation of Generic Drugs 

Office of Generic Drugs 

Center for Drug Evaluation and Research 


Cost Effective Rx


FDA 

OGD Mission 

To ensure that safe and effective 

generic drugs are available to the 

American People. 


FDA 

Legislative History 

• 1906 Pure Food and Drug Act - establishes regulation of 

Food and Drugs. 

• 1938 Food, Drug and Cosmetic Act - introduced safety 

standards. 

• 1962 Kefauver-Harris Amendments to the FDA&C Act - 

tightened safety standards and introduced requirement that 

drugs must be effective. 

• 1984 Waxman-Hatch Act - created an abbreviated 

mechanism for approval of generic copies of all drugs 

approved approved after 1962, by stating that preclinical 

and clinical tests did not have to be repeated for generics. 



Cost Effective Rx


FDA 

Hatch-Waxman Amendments 

to FFD&C Act - 1984 

• Considered one of the most successful pieces of 

legislation ever passed 

• Created the generic drug industry 

• Increased availability of generics 

• 1984 12% prescriptions were generic 

• 2000 44% prescriptions were generic - yet only 

8% of revenue 

for prescription drug 



• Compromise legislation to benefit both brand and 

generic firms 


FDA 

Hatch-Waxman Amendments 

to FFD&C Act - 1984 

• Allowed generic firms to rely on findings of 

safety and efficacy of innovator drug after 

expiration of patents and exclusivities (do not 

have to repeat expensive clinical and preclinical 

trials) 

• Allowed patent extensions and exclusivities to 

innovator firms 



Cost Effective Rx


Innovator Incentives (Patents) 

FDA 

• Prior to 1984, a patent would run for 17 years 

from issue date or 20 years from filing 

• W/H set to restore some incentive for 

innovation because pre-market approval 

requirements have increased 

• W/H may restore up to 5 years not to exceed 

14 years from the product’s approval date 


Innovator Incentives(cont.) 

FDA 

• URAA* (June 8, 1995) made all patents in 

force or filed as of this date have the longer 

term of 17 years from issuance or 20 years 

from filing 

• All patents filed after June 8, 1995 have an 

expiration date of 20 years from filing 

– *Uruguay Round Agreements Act 



Cost Effective Rx


Exclusivity Incentives 

FDA 

• NCE protection - 5 years 

• New salt or ester - 3 years 

• New use or dosage form - 3 years 

• Orphan drug status – 7 years 


Generic Incentives 

FDA 

• All approved products eligible for generic 

competition 

• Eliminated requirement for duplicative clinical 

trials 

• Created a regulatory process for faster 

approval of generic drugs 



Cost Effective Rx


FDA 

Definition of a Generic Drug 

A drug product that is comparable to a 

brand/reference listed drug product in 

dosage form, strength, route of administration, 

quality and performance characteristics, 

and intended use. 


FDA 

NDA vs. ANDA Review Process 

Brand Name Drug 

NDA Requirements 

Generic Drug 

ANDA Requirements 

1. Chemistry 1. Chemistry 

2. Manufacturing 2. Manufacturing 

3. Controls 3. Controls 

4. Labeling 4. Labeling 

5. Testing 5. Testing 

6. Animal Studies 

7. Clinical Studies 6. Bioequivalence 

8. Bioavailability 



Cost Effective Rx


Therapeutic Equivalence of 

Generic Drugs: FDA Requirements 

• Pharmacologically equivalent 

– Contains same amount of active drug 

– Meets USP standard for purity, strength, quality 

• Bioequivalent (mean AUC values are typically 

within 3-4% of each other) 

• Adequate labeling 

• Manufactured in compliance with GMP 

32 

Bioequivalence of Drugs: 

FDA Accepted Parameters 

• Single dose of reference drug and test drug given to 

24 to 36 healthy adults in a crossover design. 

Bioequivalence accepted when the 90% confidence 

interval of the ratios 

– AUC 

– C max 

– T max 

• Fall between 0.8 and 1.25 (log-transformed data) 

• The generic manufacturer’s main challenge has been 

to make a generic that was absorbed as poorly as the 

brand (IE phenytoin delayed – Dilantin) 

Meyer MC. J Clin Psychiatry 2001;62(suppl 5):4-9 

33 


Cost Effective Rx


35 


Cost Effective Rx


FDA 

What are the 

Generic Drug Requirements? 

• Same active ingredient(s) 

• Same route of administration 

• Same dosage form 

• Same strength 

• Same conditions of use 

• Compared to reference listed drug 

(RLD) - (brand name product) 


FDA 

FDA Requirements for Generic 

Ophthalmics 

According to Dr Wiley Chambers Acting 

Director of the Division of Anti-Infective and 

Ophthalmology Products at the FDA, there 

are two potential paths to market for 

generic ophthalmic solutions approved after 

1992. 



Cost Effective Rx


FDA 


Ophthalmics 

The first path involves a waiver of clinical trials if the 

generic ophthalmic solution has the same active and 

inactive ingredients in the same concentrations as the 

original. “If it does not have the same active and 

inactive ingredients in the same concentrations, then it 

would have to demonstrate bioequivalence in a clinical 

study,” says Dr. Chambers. “For ophthalmic drug 

products where the innovator (the original proprietary 

drug) was approved prior to 1992, there are cases 

where the inactive ingredients are not the same as the 

innovator. 


FDA 


Ophthalmics 

According to IMS Health, latanoprost- 

Xalatan had U.S. sales of about $711 

million in 2010. Cost is the most obvious 

allure generics have, especially for 

pharmacy benefit managers. In fact, many 

pharmacy benefit formularies have 

dropped Xalatan this year in favor of the 

generic solution. 



Cost Effective Rx



Ophthalmics 

• The following companies that offer generic latanoprost in 

the same formula as Xalatan include: 

– Brand Xalatan by Pfizer - $81.85 AWC/2.5ml 0.005% soln 

– Bausch + Lomb - $13.43 AWC/2.5ml 0.005% soln 

– Falcon Pharmaceuticals Ltd., an affiliate of Alcon Laboratories, 

Inc. (owned by Novartis) - $10.00 AWC/2.5ml 0.005% soln 

– Apotex Corp. - $53.12 AWC/2.5ml 0.005% soln 

– Greenstone LLC (owned by Pfizer) - $13.38 AWC/2.5ml 0.005% 

soln 

– Mylan – $6.90 AWC/2.5ml 0.005% soln 

– Note that all of the above have FDA Therapeutic Equivalent 

Codes of AT and are considered by the FDA therapeutically 

equivalent 

FDA Orange Book for Solutions 

• All solutions and DESI drug products containing the 

same active ingredient in the same topical dosage 

form for which a waiver of in vivo bioequivalence has 

been granted and for which chemistry and 

manufacturing processes are adequate to 

demonstrate bioequivalence, are considered 

therapeutically equivalent and coded AT. 

Pharmaceutically equivalent topical products that 

raise questions of bioequivalence, including all post- 

1962 non-solution topical drug products, are coded 

AB when supported by adequate bioequivalence 

data, and BT in the absence of such data. 

41 


Cost Effective Rx


FDA 

When can a Generic Drug 

be Marketed? 

•After patent & exclusivity protection 

ends, or 

•patent owner waives its rights, or 

•patent challenge is won, and 

•FDA requirements are met 


FDA 

APPROVED 

DRUG PRODUCTS 

WITH 

THERAPEUTIC EQUIVALENCE EVALUATIONS 

31st EDITION 

THE PRODUCTS IN THIS LIST HAVE BEEN APPROVED UNDER 

SECTION 505 OF THE FEDERAL FOOD, DRUG, AND 

COSMETIC ACT. 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

PUBLIC HEALTH SERVICE 

FOOD AND DRUG ADMINISTRATION 

CENTER FOR DRUG EVALUATION AND RESEARCH 

OFFICE OF MANAGEMENT 

DIVISION OF DATABASE MANAGEMENT 

2011 

Electronic Orange Book - http://www.fda.gov/cder/ob/ 



Cost Effective Rx


How Did the 

“Orange Book” Get it’s Nickname? 

• When the first print edition of Approved Drug Products with 

Therapeutic Equivalence Evaluations was being prepared October 

1980, staff members in the Office of Generic Drugs had to choose a 

color for the cover. The project manager suggested, "It's almost 

Halloween. How about orange?" 

“Orange Book” 

FDA 

• All FDA approved drug products listed 

(NDA’s, OTC’s & ANDA’s) 

• Therapeutic equivalence codes 

–“A” = Substitutable 

–“B” = Inequivalent, NOT substitutable 

• Expiration dates: patent and exclusivity 

• Reference Listed Drugs/brand drugs identified by 

FDA for generic companies to compare their 

proposed products with 



Cost Effective Rx


FDA Ratings 

FDA 

• “A” rated drugs are considered bioequivalent to the brand 

name original. 

– They either have been demonstrated to be so by human 

bioavailability study (“AB”) or considered inherently 

unlikely to have bioavailability problems (“AA”) 

– Other “A” designations (AN, AO, AP, AT) refer to nonoral 

formulations considered bioequivalent by the FDA 

– Only “A” rated products are interchangeable with their 

brand name equivalents by the FDA 


Levothyroxine Ratings 

FDA 

• UNITHROID (STEVENS J) 

– 0.025MG AB1 

• LEVOTHYROXINE SODIUM (MYLAN) 

– 0.025MG AB1 

• LEVOXYL (KING PHARMS) 

– 0.025MG AB1 

• SYNTHROID (ABBOTT) 

– 0.025MG AB1 



Cost Effective Rx



FDA 

• SYNTHROID (ABBOTT) 

– 0.025MG AB2 


– 0.025MG AB2 

• LEVO-T (ALARA PHARM) 

– 0.025MG AB2 


– 0.025MG AB2 

• LEVOTHYROXINE SODIUM (GENPHARM) 

– 0.025MG AB2 



FDA 

• LEVOXYL (KING PHARMS) 

– 0.025MG AB3 

• LEVO-T (ALARA PHARM) 

– 0.025MG AB3 


– 0.025MG AB3 


– 0.025MG AB3 

• LEVOTHYROXINE SODIUM (GENPHARM) 

– 0.025MG AB3 



Cost Effective Rx



FDA 

• LEVOTHROID (LLOYD) 

– 0.025MG AB4 


– 0.025MG AB4 

Therapeutic equivalence has been established between products 

that have the same AB+number TE code according to the FDA 


FDA 

Additional FDA Approved Mediactions 

with AB sub classifications 

• Norethindrone 

– Nor-QD (AB1) vs. Micronor (AB2) 

• Diltiazem 

– (AB1 thru AB4) 

• Nifedipine 

– Adalat CC (AB1) vs. Procardia XL (AB2) 

• Transdermal Nitroglycerin 

– Nitro Dur and Minitran (AB1) 



Cost Effective Rx


FDA Ratings 

FDA 

• “B” rated drugs have not been demonstrated to 

be bioequivalent by an in-vivo test. 

– These drugs are generally older drugs that were 

approved by the FDA on the basis of chemistry, 

manufacturing controls and in-vitro dissolution 

tests. 

– Less than 3% of marketed generic drugs have a 

“B” rating 


FDA Ratings 

FDA 

No well documented therapeutic differences 

between brand name originals and FDAapproved 

generics have been reported 



Cost Effective Rx


FDA 

FDA Data on Generics 

• FDA recently evaluated 2,070 human studies conducted between 

1996 and 2007. These studies compared the absorption of brand 

name and generic drugs into a person’s body. These studies were 

submitted to FDA to support approval of generics. The average 

difference in absorption into the body between the generic and the 

brand name was 3.5 percent. Some generics were absorbed slightly 

more, some slightly less. This amount of difference would be 

expected and acceptable, whether for one batch of brand name drug 

tested against another batch of the same brand, or for a generic 

tested against a brand name drug. In fact, there have been studies in 

which brand name drugs were compared with themselves as well as 

with a generic. As a rule, the difference for the generic-to-brand 

comparison was about the same as the brand-to-brand comparison. 

– Davit et al. Comparing generic and innovator drugs: a review of 12 

years of bioequivalence data from the United States Food and Drug 

Administration. Ann Pharmacother. 2009;43(10):1583-97. 


FDA 

FDA Data on Generics 

• FDA requires generic drugs to have the same 

quality and performance as brand name drugs. 

• Research shows that generics work just as well as 

brand 

FDA 

name 

Facts 

drugs. 

about Generic Drugs 

– A study evaluated the results of 38 published clinical 

trials that compared cardiovascular generic drugs to 

their brand name counterparts. There was no evidence 

that brand name heart drugs worked any better than 

generic heart drugs 

• Kesselheim et al. Clinical equivalence of generic and brand 

name drugs used in cardiovascular disease: a systematic 

review and meta-analysis. JAMA. 2008;300(21)2514-2526 



Cost Effective Rx


FDA 

FDA Facts about Generic Drugs 

• When it comes to price, there is a big difference 

between generic and brand name drugs. On 

average, the cost of a generic drug is 80 to 85 

percent lower than the brand name product. (an 

average of ~ $3 billion every week in savings) 

• Cheaper does not mean lower quality 

• FDA monitors adverse events reports for generic 

drugs 

• FDA is actively engaged in making all regulated 

products – including generic drugs – safer. 

– FDA website 4-2-2012 update 



Cost Effective Rx


American Academy of Neurology 

Consensus Statement 

“ Nonequivalence can have very serious 

effects. Decreased serum drug 

concentrations can cause breakthrough 

seizures, and increased concentrations 

can lead to toxicity……The overall cost 

to society of breakthrough seizures or 

drug toxicity may outweigh any 

economic incentive for mandating 

generic substitution” 

Neurology 1990;40:1647-1651 

FDA 

FDA Estimate of Savings 



Cost Effective Rx


Lipid Lowering Therapy 

• The current and anticipated updated NCEP-ATP- 

IV guidelines recommend using a full dose of an 

evidence based high potency statin which has 

been demonstrated to reduce clinical CV events 

before adding a second lipid altering agent 

• Are we treating to reduce events or just to achieve 

goal lipid levels? 

• LDL is primary goal (< 70mg% or < 100mg%) 

• Non-HDL is secondary goal (30 mg% above LDL 

goal) 

• New AHA/ACC triglyceride goals (optimal 


Comparison of Dose Dependent LDL Lowering 

Effects of Statins and Cost per Month 

Statin Daily Dose Average LDL Reduction Cost/Month** Generic 

Fluvastatin (Lescol) 

20mg 22% $117.59 

40mg 25% $109.19 

80mgXL 36% $145.99 

Simvastatin (Zocor) Best Buy 

5mg 26% $77.30 ($17.99) 

10mg 30% $93.99 ($19.99) 

20mg 38% $173.99 ($27.99) 

40mg 41% $173.99 ($27.99) 

80mg 47% $178.99 ($35.99) 

Cost is per 30 day supply from Drugstore.com 3-2012 

Comparison of Dose Dependent LDL Lowering 

Effects of Statins and Cost per Month 

Statin Daily Dose Average LDL Reduction Cost/Month Generic 

Atorvastatin (Lipitor) (scheduled to go genric Nov 2011) 

10mg 39% $113.70 $92.00 

20mg 43% $162.30 $120.00 

40mg 50% $162.30 $120.00 

80mg 60% $162.30 $120.00 

Rosuvastatin (Crestor) 

5mg 28% $154.99 

10mg 46% $154.99 

20mg 52% $155.98 

40mg 55% $156.99 

Cost is per 30 day supply from Drugstore.com 3-2012 


Cost Effective Rx


Proton Pump Inhibitors 

AGA Technical Review 2008 

• Ample evidence that PPIs are more effective 

than H2RAs in patients with esophageal GERD 

syndromes 

• Data supporting PPI doses higher than 

standard are minimal 

• There is no evidence that adding a nocturnal 

dose of an H2RA to twice daily PPI therapy 

improves long-term efficacy 

• Gastroenterology 2008;135:1392-1413 


• A Cochrane review of 134 treatment trials in 36,978 

patients with esophagitis, concluded that PPIs exhibit a 

better healing effect and faster symptom relief then 

H2RAs which in turn are better than placebo 

• concluded that there is no major difference in 

efficacy among the currently available PPIs 

(esomeprazole, lansoprazole, omeprazole, 

pantoprazole, rabeprazole) 

• the gain achieved by doubling the standard dose of 

PPI therapy is modest. 

• Cochrane Database Syst Rev 2007;2:CD003244 


Cost Effective Rx


Esomeprazole Vs. Lansoprazole 

Treatment of Erosive 

Esophagitis at 8 weeks 

Number 

% Healed 

(intent to treat) 

Esomeprazole 40 mg 2624 92.6% 

Lansoprazole 30 mg 2617 88.8% 

(E 40 Vs L 30 ARR 3.8%, NNT-27) 

Am J Gastroenterol 2002; 97: 575-583 

Consumer Reports Best Buy Drugs January 

2007 

• “Taking effectiveness, safety, and cost into account, we 

have chosen over-the-counter Prilosec OTC (omeprazole) 

20mg as the Consumer Reports Best Buy Drug if you need 

a PPI.” 

• A comparison table from the Drug Effectiveness Review 

Project -Oregon Health Sciences University may be 

accessed at the link : 

www.ohsu.edu/ohsuedu/research/policycenter/DERP/about/finalproducts.cfm 

• Mc Donagh and Carson, Drug Class Review on Proton Pump 

Inhibitors, Final Report, July 2006 


Cost Effective Rx



• The most important recommendation 

with any PPI is to take it 30-60 

minutes prior to a significant meal! 

• “Seventy percent of primary care physicians 

and 20% of gastroenterologists prescribe PPIs 

sub optimally, either at bedtime or unrelated to 

food intake, this is the most common cause of 

PPI failure.” 

• Gastroenterology 2008; 134: 1842-1860 

PPI’s Benefits vs. Risk? 

• Potential risks include: 

• Community and hospital acquired pneumonia 

• Risk of nosocomial C. difficile infection 

• Risk of fractures including hip fracture 

• Risk of B12, calcium and magnesium 

deficiencies 

• Risk of acid rebound 


Cost Effective Rx



• Omeprazole Generic 

Prilosec 

• 20mg caps $33.32/30 $195.99/30 

• 40mg caps $195.00/30 $291.00/30 

• Omeprazole OTC Generic Prilosec OTC 

• 20.6mg tabs $21.99/42 $24.99/42 

• Lansoprazole Generic Prevacid 

• 15mg caps $99.99/30 $195.00/30 

• 30mg caps $99.99/30 $183.25/30 

• Lansoprazole OTC Prevacid 24 

• 15mg caps $26.99/42 

Drugstore.com 3-2012 


• Pantoprazole Generic Protonix 

• 20mg tabs $15.99/30 $186.38/30 

• 40mg tabs $15.99/30 $190.00/30 

• Esomeprasole 

Nexium 

• 20mg caps $200.99/30 

• 40mg caps $189.99/30 

• Dexlansoprazole 

Dexilant 

• 30 and 60mg caps $149.99/30 

• Rabeprazole 

Aciphex 

• 20mg tabs $249.99/30 



Cost Effective Rx


Hypnotics 

• Identify the underlying problem with a good sleep 

history 

• Treat the underlying problem not just the symptom 

of insomnia 

• Diabetes 

• GERD 

• Heart failure 

• Depression 

• Pain 

• BPH 

Benzodiazepine Receptor Agonists 

Drug Onset (min) T1/2 (hr) Dose (mg) Cost/30 doses 

Sonata 10-20 1.0 5-20 $150.98 (10mg) 

zaleplon 

$34.99 (10mg) 

Ambien 10-20 1.5-2.4 5-10 $209.98 (10mg) 

Ambien CR 10-20 6.25-12.5 $193.99 (both) 

zolpidem 

$17.99 (10mg) 

Lunesta 10-30 5-6 1-3 $230.00(all) 

Rozerem 20-45 1-2.6 8 $170.08 

Triazolam 10-20 1.5-5 0.125-0.25 $17.99 (all) 

Restoril 45-60 8-20 7.5-30 $345.99 (all) 

Temazepam 45-60 8-20 7.5-30 $12.99 (15 & 30mg) 

Flurazepam 15-30 36-120 15-30 $12.99 (all) 



Cost Effective Rx


Blood Pressure Goals 

• Most important goal is to control the BP! 

• If at all possible use evidence-based medications 

and doses that have been demonstrated to reduce 

events in selected patients with hypertension 

(compelling indications – ACEI with diabetes, renal 

disease, post MI, HF, etc.) 

• Watch for the new JNC-8 guidelines which will 

incorporate weighted evidence in 2012? 

ACE Inhibitors 

• Lisinopril Generic Best Buy Zestril 

• 5 mg tabs $14.89/30 5mg $50.99/30 

• 10mg tabs $13.99/30 10 mg $55.11/30 

• 20mg tabs $14.99/30 20mg $57.99/30 

• 30mg tabs $20.99/30 30mg $71.99/30 

• 40mg tabs $17.99/30 40mg $73.99/30 

• Lisinopril/HCTZ Generic 

Zestoretic 

• 10/12.5mg $23.99/30 10/12.5mg $56.78/30 

• 20/12.5mg $21.99/30 20/12.5mg $60.05/30 

• 20/25mg $21.99/30 20/25mg $59.99/30 

• Drugstore.com 4/2012 


Cost Effective Rx



• Ramipril Generic 

Altace 

• 2.5mg caps $49.99/30 2.5mg $77.99/30 

• 5mg caps $52.99/30 5mg $81.99/30 

• 10mg caps $62.99/30 10mg $90.99/30 

• Quinapril Generic 

Accupril 

• 5mg tabs $23.99/30 5mg $69.27/30 

• 10mg tabs $19.99/30 10mg $62.99/30 

• 20mg tabs $26.97/30 20mg $67.99/30 

• 40mg tabs $21.99/30 40mg $66.99/30 

• Drugstore.com 4-2012 


• Benazepril Generic 

Lotensin 

• 5mg tabs $24.33/30 $62.80/30 

• 10mg tabs $25.99/30 $67.99/30 

• 20mg tabs $25.99/30 $64.99/30 

• 40mg tabs $25.99/30 $67.99/30 

• Benazepril/HCTZ Generic 

Lotensin HCT 

• 10/12.5mg tabs $22.99/30 $62.99/30 

• 20/12.5mg tabs $26.99/30 $65.99/30 

• 20/25mg tabs $26.99/30 $63.99/30 



Cost Effective Rx


Angiotensin Receptor Blockers (ARB’s) 

• Losartan Generic 

Cozaar 

• 25mg tabs $50.10/30 $64.99/30 

• 50mg tabs $67.88/30 $86.86/30 

• 100mg tabs $83.49/30 $118.32/30 

• Losartan/HCTZ Generic 

Hyzaar 

• 50/12.5mg tabs $75.05/30 $96.05/30 

• 100/12.5mg tabs $102.23/30 $130.66/30 

• 100/25mg tabs $102.23/30 $130.84/30 

• AWP 2012 


• Valsartan (Diovan) generic 9/2012 

• 40mg tabs $89.99/30 

• 80mg tabs $100.99/30 

• 160mg tabs $111.99/30 

• 320mg tabs $136.99/30 

• Candesartan (Atacand) generic 12/2012 

• 4mg tabs $84.99/30 

• 8mg tabs $83.99/30 

• 16mg tabs $85.99/30 

• 32mg tabs $111.99/30 



Cost Effective Rx



• Telmisartan (Micardis) each tab wrapped in foil 

(hydroscopic) 

• 20mg tabs $123.99/30 

• 40mg tabs $123.99/30 

• 80mg tabs $122.99/30 

• Olmesartan (Benicar) 

• 5mg tabs $78.99/30 

• 20mg tabs $95.99/30 

• 40mg tabs $134.99/30 



• Irbesartan (Avapro) generic 3/2012 

• 75mg tabs $95.91/30 

• 150mg tabs $98.99/30 

• 300mg tabs $119.99/30 

• Eprosartan (Teveten) 

• 400mg tabs $90.00/30 

• 600mg tabs $119.99/30 

• Azilsartan (Edarbi) 

• 40 mg tabs $85.99/30 

• 80 mg tabs $89.99/30 



Cost Effective Rx


Direct Renin Inhibitor 

• Aliskiren (Tekturna) 

• 150mg tabs $97.92/30 

• 300mg tabs $123.00/30 

• Aliskiren/HCTZ (Tekturna HCT) 

• 300/25 tabs $123.41/30 

• Aliskiren/Valsartan (Valturna) AVOID in patients 

with DM 

• 150/160 tabs $95.99/30 

• 300/320 tabs $117.99/30 


Amlodipine 

• Amlodipine Generic Best Buy! Norvasc 

• 2.5mg tabs $21.97/100 $245.51/100 

• 5mg tabs $25.54/100 $259.07/100 

• 10mg tabs $26.66/100 $333.29/100 

• Benazepril/Amlodipine Generic Lotrel 

• 2.5/10mg caps $69.99/30 $123.99/30 

• 5/10mg caps $76.99/30 $127.99/30 

• 5/20mg caps $69.99/30 $117.93/30 

• 5/40mg caps $115.99/30 $145.97/30 

• 10/20mg caps $89.99/30 $158.99/30 

• 10/40mg caps $115.99 $175.00/30 



Cost Effective Rx


Evidence Based Diuretics 

• Chlorthalidone Generic 

• 25mg tabs $11.97/100 (FUL $5.10/100) AWP 

• 50mg tabs $12.97/100 (FUL $5.50/100) 

• Indapamide Generic Lozol 

• 1.25mg tabs $15.99/90 (FUL $10.35/100) $122.21/100 

• 2.5mg tabs $19.97/90 (FUL $11.25/100) 

• Spironolactone Generic Aldactone 

• 25mg tabs $33.30/100 (FUL $30.00/100) $113.30/100 

• 50mg tabs $52.19/100 $195.52/100 

• Eplerenone Generic Inspra 

• 25mg tabs $275.99/90 $424.73/90 

• 50mg tabs $275.99/90 $425.09/90 


Evidence Based Beta Blockers in HF 

• Metoprolol succinate (Toprol XL) MERIT-HF 

• 25 mg tabs $46.99/30 Brand $29.99/30 generic 




• Carvedilol (Coreg) COMET/COPERNICUS 

• 3.125 mg tabs $138.99/60 Brand $34.99/60 generic 

• 6.25 mg tabs $150.96/60 Brand $29.98/60 

• 12.5 mg tabs $149.00/60 Brand $31.98/60 generic 




Cost Effective Rx


Evidence Based Beta Blockers in HF 

• Coreg CR (Not evidence based!) QD no generic 

• 10 mg caps (3.125 BID equivalent) $141.99/30 

• 20 mg caps (6.25 BID equivalent) $141.99/30 

• 40 mg caps (12.5 mg BID equivalent) $141.99/30 

• 80 mg caps (25 mg BID equivalent) $143.99/30 

• Bisoprolol fumarate(Zebeta) Not FDA approved but 

evidence-based CIBIS-II 

• 5 mg tabs $35.99/30 Brand $114.43/30 

• 10 mg tabs $37.99/30 Brand $114.43/30 


ADA/EASD Consensus Algorithm for the Initiation 

and Adjustment of Therapy 

Diabetes Care 2009; 32:193–203 

a - Sulfonylureas other than glybenclamide (glyburide) or 

chlorpropamide. 


Cost Effective Rx


Avoid Use of Glyburide? 

In-hospital mortality in patients on sulfonylureas before admission (n = 459) according to the type of 

sulfonylureas and stratified by specific subgroups (J Clin Endocrinol Metab, November 2010, 95(11):4993–5002) 

UK Prospective Diabetes Study 

Glucose Interventional Trial 

Dietary 

Run-in 

744 

Diet failure 

FPG >15 mmol/l 

Randomisation 

1977-1991 

2,729 

Intensive 

with sulfonylurea/insulin 

Trial end 

1997 

Intensive 

P 

5,102 

Newly-diagnosed 

type 2 diabetes 

4209 

1,138 (411 overweight) 

Conventional 

with diet 

Conventional 

P 

149 

Diet satisfactory 

FPG


Any Diabetes Related Endpoint (%) at 10 

years 

• Diet + Metformin 28.7% 

• Diet + Sulf/Insulin 36.8% 

• Diet only 38.9% 

• RRR 26.2% with diet + metformin vs. diet alone 

• ARR 10.2% 

• NNT 10 

All Cause Mortality (%) at 10 years 


• Diet + Sulf/Insulin 20% 

• Diet alone 21.7% 

• RRR 32.7% with metformin + diet vs. diet alone 

• ARR 7.1% 

• NNT 14 


Cost Effective Rx


Myocardial Infarction (%) 

at 10 years 




• RRR 36% with diet + metformin vs, diet alone 

• ARR 6.4% 

• NNT 16 

Stroke (%) at 10 years 




• RRR 44.4% with diet + metformin vs, diet + 

sulf/insulin 

• ARR 2.8% 

• NNT 36 


Cost Effective Rx


Long-term Effects of Metformin on Metabolism 

and Microvascular and Macrovascular Disease 

in Patients With Type 2 Diabetes Mellitus Treated with 

Insulin Arch Intern Med. 2009;169(6):616-625 

•390 patients treated with insulin in the 

outpatient clinics of 3 hospitals in a 

randomized, placebo-controlled trial with a 

follow-up period of 4.3 years. Either 

metformin hydrochloride, 850 mg, or placebo 

(1-3 times daily) was added to insulin therapy. 

•The primary end point was an aggregate of 

microvascular and macrovascular morbidity 

and mortality. The secondary end points were 

microvascular and macrovascular morbidity 

and mortality independently. 

“Hyperinsulinemia the Outcome of its 

Metabolic Effects (HOME)” 

Long-term Effects of Metformin on Metabolism 

and Microvascular and Macrovascular Disease 

in Patients With Type 2 Diabetes Mellitus Treated with 

Insulin Arch Intern Med. 2009;169(6):616-625 

Results: 

• Metformin treatment prevented weight gain (mean weight gain, −3.07 kg 

[range, −3.85 to −2.28 kg]; P.001), 

• Improved glycemic control (mean reduction in HbA1c level, 0.4% 

percentage point [95% CI, 0.55-0.25]; P.001), despite the aim of similar 

glycemic control in both groups, 

• Reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 

24.91-14.36 IU/d]; P.001). 

• Metformin was not associated with an improvement in the primary end 

point. 

• It was, however, associated with an improvement in the secondary, 

macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P=.02), 

which was partly explained by the difference in weight. 

• The number needed to treat to prevent 1 macrovascular end point was 

16.1 (95% CI, 9.2-66.6). 

• These sustained beneficial effects support the policy to continue 

metformin treatment after the introduction of insulin in any patient with 

DM2, unless contraindicated. 


Cost Effective Rx


Risk of fatal and nonfatal lactic acidosis with 

metformin use in type 2 diabetes mellitus 

The Cochrane Library 2010, Issue 4 

• Main results: 

– Pooled data from 347 comparative trials and cohort studies 

revealed no cases of fatal or nonfatal lactic acidosis in 70,490 

patient years of metformin use or in 55,451 patients-years in 

the non-metformin group. Using Poisson statistics the upper 

limit for the true incidence of lactic acidosis per 100,000 

patient-years was 4.3 cases in the metformin group and 5.4 

cases in the non-metformin group. 

– There was no difference in lactate levels, either as mean 

treatment levels or as a net change from baseline, for 

metformin compared to non-metformin therapies. 

• Authors’ conclusions: 

– “There is no evidence from prospective comparative trials or 

from observational cohort studies that metformin is associated 

with an increased risk of lactic acidosis, or with increased 

levels of lactate, compared to other anti-hyperglycemic 

treatments.” 

Proposed Recommendations for Use of 

Metformin Based on e-GFR 

Diabetes Care 2011;34:1435 

eGFR (ml/min per 1.73m2) 

Action 

>60 No renal contraindication to metformin 

>45 Continue use 

Increase monitoring of renal function (every 3–6 

months) 

30 Prescribe metformin with caution 

Use lower dose (e.g., 50%, or half-maximal dose) 

Closely monitor renal function (every 3-6 months) 

Do not start new patients on metformin 


Metformin 

• Metformin HCl Immediate release tabs 

• 500 mg $12.99/60 Glucophage $69.99/60 

• 850 mg $61.99/60 Glucophage $113.29/60 

• 1000 mg $31.97/60 Glucophage $141.08/60 

• Metformin Extended release tabs 

• 500 mg $18.00/60 Glucophage XR $69.99/60 

Glumetza $233.40/60 

• 750 mg $65.98/60 Glucophage XR $107.98/60 

• 1000 mg $169.62/60 Glumetza $515.98/60 


Sulfonylureas 

• Glipizide Immediate release 

• 5 mg $13.45/60 Glucotrol $43.99/30 

• 10 mg $13,00/60 Glucotrol $81.89/60 

• Glipizide XL (Extended release) 

• 10 mg $23.99/30 Glucotrol XL $48.99/30 

• Glimepiride 

• 2 mg $13.99/30 Amaryl $39.99/30 

• 4 mg $14.99/30 Amaryl $63.99/30 

• Glyburide AVOID! 

• 5mg $18.99/30 Micronase $41.99/30 

Diabeta $45.75/30 



Cost Effective Rx


Insulins 

• Regular Insulin (10cc vial) 

• Humalin R $73.99 Novolin R $75.99 

• ReliOn (Humalin R) $23.67 Walmart 

• NPH Insulin (10cc vial) 

• Humalin N $73.99 Novolin N $75.99 

• ReliOn (Humalin N) $23.67 Walmart 

• 70/30 NPH/Regular Insulin (10cc vial) 

• Humalin 70/30 $73.99 

• Novolin 70/30 $75.99 

3 cc pen $135.99/3 pens 

• ReliOn (Humalin 70/30) $23.67 Walmart 


Insulins 

• Insulin glargine - Lantus 

• 10cc vial $124.99/vial 

• SoloStar pen (3cc) $234.99/5 pens 

• Insulin detimir – Levemir 


• FlexPen (3cc) $242.99/5 pens 



Cost Effective Rx


Insulins 

• Insulin lispro – Humalog 

• 10 cc vial $137.98/vial 

• Kwik Pen (3cc) $268.99/5 pens 

• Insulin aspart – Novolog 


• FlexPen (3cc) $268.99/5 pens 

• Insulin glulisine – Apidra 

• SoloStar (3cc) $218.28/5 pens 


Insulins 

• Insulin lispro/NPH – Humalog Mix 

• 50/50 Kwik Pen (3cc) $271.00/5 pens 

• 75/25 Kwik Pen (3cc) $281.43/5 pens 

• Insulin aspart/NPH – Novolog Mix 

• 70/30 FlexPen (3cc) $258.98/5 pens 



Cost Effective Rx


Pioglitazone - Actos 

• Actos 15 mg tabs $193.48/30 

• Actos 30 mg tabs $289.98/30 

• Actos 45 mg tabs $310.00/30 

• ActosPlus Met XR 30/1000 mg tabs $309.99/30 


GLP-1 Agonists 

• Exenatide – Byetta 

• 5mcg/0.02ml Solution 1.2ml Pen $350.28/pen AWP 

• 10mcg/0.04ml Solution 2.4ml Pen $350.28/pen 

• Extenatide extended release – Bydureon 

• 2mg/vial in cartons of 4 doses (28 day supply) 

• $325.99 Drugstore.com 4-2012 

• Liraglutide – Victoza 

• 18 mg/3 mL Pen in box of 2 pens $312.07 AWP 

• 18 mg/3 mL Pen in box of 3 pens $468.11 AWP 


Cost Effective Rx


DPP-4 Inhibitors 

• Sitagliptin – Januvia 

• 25 mg tabs $243.60/30 AWP 

• 50 mg tabs $243.60/30 AWP 

• 100mg tabs $243.60/30 AWP 

• Sitagliptin + metformin IR – Janumet (BID) 

• 50/500 mg tabs $243.60/60 AWP 

• 50/1000 mg tabs $243.60/60 AWP 

• Sitagliptin + metformin XR – Janumet XR 

• 50/500 mg tabs 

• 50/1000 mg tabs 

• 100/1000 mg tabs 


• Saxagliptin – Onglyza 

• 2.5 mg tabs $243.58/30 AWP 

• 5 mg tabs $243.58/30 AWP 

• Saxagliptin + metformin XR – Kombiglyze XR 

• 2.5/1000 mg tabs $243.58/30 AWP 

• 5/500 mg tabs $243.58/30 AWP 

• 5/1000 mg tabs $243.58/30 AWP 


Cost Effective Rx



• Linagliptin – Tradjenta 

• 5 mg tabs $241.00/ 30 Drugstore.com 4-2012 

• Linagliptin + metformin IR – Jentaduento (BID) 

• 2.5/500 mg tabs 

• 2.5/850 mg tabs 

• 2.5/1000 mg tabs 


Cost Effective Rx

Proton Pump Inhibitors - CME Conferences

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