WOW February 2017

Page 3 Volume 17; Issue 2
Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker:
Cost Saving Projections via Therapeutic Interchange
Meera Vachhani, PharmD, PGY1 Pharmacotherapy Resident
The angiotensin-converting enzyme inhibitors (ACEI) and angiotensin
receptor blockers (ARB) drug class review completed for
the Johns Hopkins Health System reviewed efficacy, cost, and
safety among these medications. Based on this information, the
drugs’ formulary status and therapeutic interchange protocols were
developed for the JHHS.
The formulary agents selected within the ACEI and ARB drug
classes are captopril, enalapril, enalaprilat, and lisinopril, and
irbesartan, losartan, and valsartan, respectively. Therapeutic interchange
protocols were developed to interchange nonformulary
ACEIs to lisinopril, and nonformulary ARBs to losartan. The implementation
of the therapeutic interchanges outlined above are
projected to result in approximately $25,000 in cost savings annually.
These projections are calculated based on 12-month volume
history from McKesson. Of note, a new combination therapy,
valsartan and sacubitril (Entresto®), was also added to the JHHS
formulary with restriction to continuation of a home medication.
New initiations are restricted to patients on a cardiology service or
those with a cardiology consult.
The ACEI/ARB therapeutic interchange protocols are currently
being built within Epic. Communication to the department will be
disseminated prior to the build changes going live in Epic. The
therapeutic interchange details are outlined in Lexicomp.
References:
1. Furberg CD and Pitt B. Are all angiotensin-converting enzyme inhibitors
interchangeable? J Am Coll Cardiol 2001; 37: 1456-60.
2. Heran BS et al. Blood pressure lowering efficacy of angiotensin receptor
blockers for primary hypertension. Cochrane Database of
S y s t e m a t i c R e v i e w s 2 0 0 8 ; 4 : C D 0 0 3 8 2 2 . D O I :
10.1002/14651858.CD003822.pub2.
3. Matchar DB et al. Systematic review: comparative effectiveness of
angiotensin-converting enzyme inhibitors and angiotensin II receptor
blockers for treating essential hypertension. Ann Intern Med
2008; 148: 16-29.
Granisetron Transdermal System for the Prevention of
Chemotherapy-Induced Nausea and Vomiting
Olivia Akah, Notre Dame of Maryland University, PharmD Candidate 2019
Lauren McBride, PharmD, BCOP, Clinical Pharmacy Specialist, Oncology
Chemotherapy has helped millions of people in the fight against
cancer by destroying cancerous cells. Unfortunately, healthy noncancerous
cells are also destroyed in the process, leading to various
unpleasant side effects. Chemotherapy-induced nausea and vomiting
(CINV) is potentially the most severe and distressing adverse
effect experienced by patients undergoing chemotherapy. To prevent
CINV associated with chemotherapy regimens with a high
emetic risk (i.e., incidence of emesis exceeds 90% if no antiemetics
are administered), the American Society of Clinical Oncology
(ASCO) currently recommends a 3-drug antiemetic regimen consisting
of a NK-1 receptor antagonist (e.g., aprepitant, fosaprepitant)
a type 3 serotonin (5-HT3) receptor antagonist (e.g., granisetron,
ondansetron, palonosetron), and dexamethasone. 1,2
Granisetron is a first generation selective inhibitor of type 3 serotonergic
(5-HT3) receptors with little or no affinity for other serotonin
receptors. It is an antiemetic indicated for the prevention of
nausea and vomiting in patients receiving moderately and/or highly
emetogenic chemotherapy regimens of up to 5 consecutive days
of duration. The drug is structurally and pharmacologically related
to ondansetron. The antiemetic activity of granisetron appears to
be mediated both centrally and peripherally via inhibition of 5-
HT3. 2 Serotonin receptors of the 5-HT3 type are located peripherally
on vagal nerve terminals and centrally in the chemoreceptor
trigger zone of the area postrema. During chemotherapy, mucosal
enterochromaffin cells release serotonin, which stimulates 5-HT3
receptors. This evokes vagal afferent discharge, inducing vomiting.
3
In select patients who are unable to swallow or digest tablets because
of emesis, transdermal antiemetics such as granisetron transdermal
system may be of value. In September 2008, the FDA approved
the use of granisetron transdermal system (GTS) for
CINV. The patch containing 3.1 mg of granisetron/24 hours is
applied approximately 24 to 48 hours before the first dose of
chemotherapy; maximum duration of the patch is 7 days. 3,4
The efficacy and tolerability of transdermal granisetron for the
control of CINV associated with moderately and highly emetogenic
multi-day chemotherapy was assessed in a phase III clinical trial.
The trial (n=641) was a randomized, non-inferiority, active control,
double-blind, double-dummy, parallel group, multinational
study that compared GTS to oral granisetron. Patients were randomized
to oral (2 mg/day, 3-5 days) or transdermal granisetron
(one GTS patch, 7 days), before receiving multi-day chemotherapy.
The primary endpoint was complete control of CINV (i.e. no
vomiting/retching, no more than mild nausea, no rescue medication)
from chemotherapy initiation until 24 h after final administration.
The pre-specified non-inferiority margin was 15%. Results
showed that GTS displayed non-inferiority to oral granisetron;
complete control was achieved by 60% of patients in the
GTS group and 65% in the oral granisetron group (treatment difference,
−5%; 95% confidence interval, −13% to +3%). Both
treatments were well tolerated. 5
The most common adverse effect of GTS is constipation. Skin
reactions such as rash, redness, and itching may occur at the site of
application. GTS is contraindicated in patients with known hypersensitivity
to granisetron or to any of the components of the
patch. The use of granisetron may mask a progressive ileus and/or
gastric distention caused by the underlying condition. Development
of serotonin syndrome has been reported with 5-HT3 receptor
antagonists. Most reports have been associated with concomitant
use of serotonergic drugs such as selective serotonin reuptake
inhibitors (SSRI’s), mirtazapine, lithium, tramadol,
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