Ondansetron

 MOA
o Serotonin 5-HT3 receptor antagonist
 Onset & Dosing
o ~30 minutes
o 4mg IV as a single dose at the end of surgery. Repeat doses given in the context
of inadequate relief are generally ineffective [4].
 Indications
o Cancer chemotherapy-induced nausea and vomiting, postoperative nausea
and/or vomiting, radiotherapy-associated nausea and vomiting.
 Contraindications
o The only true contraindications to ondansetron use are known hypersensitivity
reaction to ondansetron or its components, and concomitant use with
apomorphine
 Adverse Effects
o The most commonly reported side effects of the IV formulation of ondansetron
are headache and constipation.
o There is also a potential of ondansetron causing prolongation of the QT interval,
and should therefore be avoided in patients who are at risk for QTc prolongation
(ie congenital long QT syndrome, CHF, bradyarrhythmias, patients already taking
QT prolonging medications) [2].
o “The number needed to harm (NNH) is 36 for headache, 31 for elevated liver
enzymes, and 23 for constipation” [3].
 Cost
o Ondansetron 4 mg/ 2 ml: $0.42
 Efficacy
o According to the 2022 PONV Consensus Guidelines: “The NNT is 6 for prevention
of vomiting and 7 for nausea” [3]
o As a single agent ondansetron is less effective than: ramosetron*, granisetron*,
palonosetron*, oral aprepitant, and IV fosaprepitant*. It is more effective than IV
metoclopramide, and dexmedetomidine [3].
o *not currently on MUSC formulary
 Alternatives: other well-studied 5-HT3 receptor antagonists include the drugs listed
below. While several are considered superior to ondansetron in their efficacy, none are
currently available on the MUSC formulary.
o Granisetron: 5-HT3 receptor antagonists with similar or slightly better efficacy
than ondansetron.
o Palonosetron: second generation serotonin receptor antagonist that
allosterically binds to the 5-HT3 and inhibits the NK1 receptor resulting in a 40
hour half-life. Palonosetron has been shown to be more effective than
 ondansetron 4mg and 8mg, dexamethasone, and the other listed 5-HT3 receptor
antagonists [5][6]. Palonosetron also does not appear to prolong the QT interval.
o Ramosetron, Tropisetron, and Dolasetron: not available for commercial use in
the US.

Aprepitant/Fosaprepitant
 MOA
o NK1 receptor antagonist
 Onset & Dosing
o Time to peak plasma concentrations: ~3hrs following a single 40mg dose or
~4hrs when 125mg given followed by 80mg for two days.
o Terminal half-life: 9 to 12 hrs
 Indications
o The IV formulation is currently only indicated for the prevention of
chemotherapy-induced nausea and vomiting. The oral formulation (Emend) is
indicated for the same condition, and also for the prevention of PONV.
o The 2022 PONV Consensus guidelines state that “NK1 receptor antagonists may
be useful prophylactic antiemetics when postoperative emesis is highly
undesirable, such as in gastric and neurosurgery.”
 Contraindications
o Hypersensitivity to aprepitant or any component of the formulation
 Adverse Effects
o The most significant adverse effects of aprepitant use are: hypersensitivity
reactions, decreased PT/INR when given with warfarin. The IV formulation also is
prepared in an emulsion with several inactive ingredients, including: alcohol, egg
lecithin, soybean oil, and sucrose.
 Cost
o Fosaprepitant 150 mg/ 10 ml: $305.87
 Efficacy
o A Cochrane network meta analysis of RCTs including 97,516 patients found that
when compared against 44 single drugs and 51 drug combinations, the NK1
receptor antagonists single agent for prevention of PONV and as effective as
several combination therapies [7]
o Aprepitant has been shown to reduce the incidence of vomiting on POD1 and
POD2.
 Alternatives
o Casopitant and Rolapitant are not approved for the treatment or prevention of
PONV.
o Vestipitant: overall noninferior in efficacy to ondansetron, but with lower rates
of emesis.
1. Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the
prevention of postoperative nausea and vomiting. N Engl J Med.
2004;350(24):2441-2451. doi:10.1056/NEJMoa032196

2. Center for Drug Evaluation and Research. New information regarding qt prolongation
with Ondansetron (zofran). U.S. Food and Drug Administration.
https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-
new-information-regarding-qt-prolongation-ondansetron-zofran. Accessed November 14,
2022.
3. Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the
Management of Postoperative Nausea and Vomiting [published correction
appears in Anesth Analg. 2020 Nov;131(5):e241]. Anesth Analg. 2020;131(2):411-
448. doi:10.1213/ANE.0000000000004833
4. Dershwitz M, Conant JA, Chang Y, Rosow CE, Connors PM. A randomized, double-
blind, dose-response study of ondansetron in the prevention of postoperative
nausea and vomiting. J Clin Anesth. 1998;10(4):314-320. doi:10.1016/s0952-
8180(98)00035-x
5. Singh PM, Borle A, Gouda D, et al. Efficacy of palonosetron in postoperative
nausea and vomiting (PONV)-a meta-analysis [published correction appears in J
Clin Anesth. 2016 Dec;35:492]. J Clin Anesth. 2016;34:459-482.
doi:10.1016/j.jclinane.2016.05.018
6. Xiong C, Liu G, Ma R, Xue J, Wu A. Efficacy of palonosetron for preventing
postoperative nausea and vomiting: a systematic review and meta-analysis. Can J
Anaesth. 2015;62(12):1268-1278. doi:10.1007/s12630-015-0457-1
7. Weibel S, Jelting Y, Pace NL, et al. Drugs for preventing postoperative nausea and
vomiting in adults after general anaesthesia: a network meta-analysis (protocol).
Cochrane Database Syst Rev. 2017;11:CD012859.