Ondansetron

Ondansetron, marketed under the brand name Zofran, is a

medication used to prevent nausea and vomiting caused by
cancer chemotherapy, radiation therapy, or surgery.[1] It is also
useful in gastroenteritis.[2][3] It has little effect on vomiting
caused by motion sickness.[4] It can be given by mouth, or by
injection into a muscle or into a vein.[1]

Common side effects include diarrhea, constipation,

headache, sleepiness, and itchiness.[1] Serious side effects
include QT prolongation and severe allergic reaction.[1] It
appears to be safe during pregnancy but has not been well
studied in this group.[1] It is a serotonin 5-HT3 receptor
antagonist.[1] It does not have any effect on dopamine
receptors or muscarinic receptors.[5]

Ondansetron was patented in 1984 and approved for medical

use in 1990.[6] It is on the World Health Organization's List of
Essential Medicines, the most effective and safe medicines
needed in a health system.[7] It is available as a generic
medication.[1] The wholesale cost of the injectable form in the
developing world is about US$0.10 to
Ondansetron
US$0.76 per dose.[8] In the United
States it costs about US$1.37 per
tablet.[1] In 2016 it was the 91st most
prescribed medication in the United
States with more than 8 million
prescriptions.[9]

Clinical data
Medical uses Trade Zofran,
names
Although an effective antiemetic agent, Ondisolv,
others
the high cost of brand-name
AHFS/Drugs.com Mono
ondansetron initially limited its use to
MedlinePlus a601209
controlling postoperative nausea and
Pregnancy AU: B1
vomiting and chemotherapy-induced
category
nausea and vomiting.[10] US: B (No
risk in non-
human
Cancer treatment studies)

The 5-HT3 receptor antagonists are the Routes of By

primary drugs used to treat and prevent administration
mouth,
chemotherapy-induced nausea and rectal,

vomiting and radiotherapy-induced IV, IM

nausea and vomiting. ATC code A04AA01

(WHO )
Postoperative Legal status
Legal AU: S4
status
A number of medications including (Prescription
ondansetron appear to be effective in only)

controlling postoperative nausea and CA: ℞-only

vomiting. It is more effective than UK: POM

(Prescription
metoclopramide, and less sedating
only)
than cyclizine or droperidol.
US: ℞-only

Pharmacokinetic data
Pregnancy Bioavailability ~60%

Ondansetron is used off-label to treat Protein 70–76%

binding
morning sickness and hyperemesis Metabolism Liver
gravidarum of pregnancy. It is typically (CYP3A4,
used after trials of other drugs have CYP1A2,
failed.[11] CYP2D6)
Elimination 5.7 hours
There appears to be a low risk of harm half-life
Excretion Kidney
to the baby with use during pregnancy,
though there may be an increase in Identifiers

heart problems among the IUPAC name

babies.[12][13] (RS)-9-Methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3-dihydr

o-1H-carbazol-4(9H)-one

Ondansetron is in pregnancy category CAS 99614-02-

Number
B in the US.[14] It is not known if 5  

PubChem 4595
CID
ondansetron is excreted in breast IUPHAR/BPS 2290

milk.[14] DrugBank DB00904  

ChemSpider 4434  

UNII
Cyclic vomiting syndrome 4AF302ESOS
KEGG D00456  

Ondansetron is one of several

ChEMBL ChEMBL46  
antiemetic agents used during the
vomiting phase of cyclic vomiting CompTox DTXSID8023
syndrome.[15] Dashboard
(EPA)
ECHA 100.110.918
InfoCard
Gastroenteritis
Chemical and
Trials in emergency department
physical data
settings support the use of Formula C18H19N3O
ondansetron to reduce vomiting
Molar 293.4
associated with gastroenteritis and mass
g/mol g·mol−1
dehydration.[16] A retrospective review 3D model Interactive
found it was used commonly for this (JSmol)
image
purpose, being administered in over
SMILES
58% of cases. Its use reduced hospital O=C3c2c1ccccc1n(c2CCC3Cn4ccnc4C)C

InChI
admissions, but was also associated InChI=1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-
16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-1
0,13H,7-8,11H2,1-2H3 

with higher rates of return visits to the Key:FELGMEQIXOGIFQ-UHFFFAOYSA-N 

  (verify)
emergency department. Furthermore,
people who had initially received
ondansetron were more likely to be admitted on the return
visit than people who had not received the drug. However, this
effect may simply be due to the agent being used more
frequently in people who present with more severe illness. Its
use was not found to mask serious diagnoses.[17]

Special populations
Children

Ondansetron has rarely been studied in people under 4 years

of age. As such, little data is available to guide dosage
recommendations.[14]

Elderly

It is not necessary to adjust the dosage for people under 75

years of age. The use of ondansetron has not been studied in
people older than 75 years of age, and it is not known if
dosage should be adjusted for this group.[14]

Poor liver function

The maximum recommended dose for people with severe

liver function impairment is 8 mg/day. In these people,
ondansetron is cleared from the body at half to one-third the
rate as in healthy people. The concentration of ondansetron in
body tissues as opposed to plasma is also higher than in
healthy people.[14]

Adverse effects
Headache is the most common adverse effect.[18] A review of
use for post-operative nausea and vomiting found that for
every 36 people treated, one would experience headache,
which could be severe.[19]

Constipation, diarrhea, and dizziness are other commonly

reported side effects.[1] It is broken down by the hepatic
cytochrome P450 system and it has little effect on the
metabolism of other drugs broken down by this system.
Anecdotally, ototoxicity has also been reported if injected too
quickly.[1]

QT prolongation

Use of ondansetron has been associated with prolongation of

the QT interval, which can lead to a potentially fatal heart
rhythm known as torsades de pointes. Although this may
happen in any person with any formulation, the risk is most
salient with the injectable (intravenous) form of the drug and
increases with dose. The risk is also higher in people taking
other medicines that prolong the QT interval, as well as in
people with congenital long QT syndrome, congestive heart
failure, and/or bradyarrhythmias. As such, single doses of
injectable ondansetron should not exceed 16 mg at one time.
(Oral dosing recommendations remain intact, including the
recommendation of a single 24-mg oral dose when indicated.)
Electrolyte imbalances should be corrected before the use of
injectable ondansetron. People are cautioned to seek
immediate medical care if symptoms such as irregular
heartbeat/palpitations, shortness of breath, dizziness, or
fainting occur while taking ondansetron.[20]

Overdose

No specific treatment is available for ondansetron overdose;

people are managed with supportive measures. An antidote
to ondansetron is not known.[14]

Pharmacodynamics
Ondansetron is a highly specific and selective serotonin 5-HT3
receptor antagonist, with low affinity for dopamine receptors.
The 5-HT3 receptors are present both peripherally on vagal
nerve terminals and centrally in the chemoreceptor trigger
zone of the area postrema in the medulla. Serotonin is
released by the enterochromaffin cells of the small intestine
in response to chemotherapeutic agents and may stimulate
vagal afferents (via 5-HT3 receptors) to initiate the vomiting
reflex. It is thought that ondansetron's antiemetic action is
mediated mostly via antagonism of vagal afferents with a
minor contribution from antagonism of central receptors.[21]

History

A vial of Zofran 4 mg containing ondansetron for intravenous injection

Ondansetron (marketed under the brand name Zofran) was

developed in the mid-1980s by GlaxoSmithKline in London. It
was granted US patent protection in September 1987,[22]
received a use patent June 1988,[23] and was approved by the
US FDA in January 1991. It was granted another divisional
patent in November 1996.[24] Finally, owing to
GlaxoSmithKline's research on pediatric use, ondansetron's
patent protection was extended until December 2006.[25] By
this final year of its patent (2006), Zofran had become the
20th highest-selling brand-name drug in the United States,
with sales of US$1.3 billion in the first 9 months of 2006 (80%
from the US).[26] The first generic versions were approved by
the US FDA in December 2006, with marketing approval
granted to Teva Pharmaceuticals USA and SICOR
Pharmaceuticals.[27]

Society and culture

Publication bias

In 1997, ondansetron was the subject of a meta-analysis case

study published in the British Medical Journal. Researchers
examined 84 trials, with 11,980 people receiving ondansetron,
published between 1991 and September 1996. Intravenous
ondansetron 4 mg versus placebo was investigated in 16
reports and three further reports which had been duplicated a
total of six times. The number needed to treat (NNT) to
prevent vomiting within 24 hours was 9.5, with 95%
confidence interval 6.9 to 15, in the 16 nonduplicated reports.
In the three duplicated reports, the NNT was significantly
lower at 3.9 (3.3 to 4.8). When all 25 reports were combined,
the apparent NNT improved to 4.9 (4.4 to 5.6). Inclusion of
duplicate reports led to a 23% overestimation of
ondansetron's antiemetic efficacy.[28]
In addition, the authors found the covert duplication of reports
on ondansetron was not easy to detect, because of lack of
cross-referencing between papers, and reports containing
duplicate findings were cited in eight reviews of the drug.[28]
Their analysis was a subject of an editorial in the Journal of
the American Medical Association in 1999.[29]

Availability

Ondansetron is a generic drug and is available in many

countries under many brand names.[30]

Research
Psychiatric disorders

A 2006 double-blind, randomized controlled trial indicated

ondansetron may have value in the treatment of
schizophrenia, as an adjunct to haloperidol. The study found
the combination to significantly improve negative
schizophrenia symptoms, and people taking both drugs
experienced fewer of the adverse effects commonly
associated with haloperidol.[31] An earlier, smaller, open-label
trial had found ondansetron to be useful in treating
antipsychotic-induced tardive dyskinesia in people with
schizophrenia, and the study patients also showed significant
improvement in the disease's symptoms.[32][33]

Early studies have also examined ondansetron as a possible

treatment for psychosis resulting from advanced Parkinson's
disease.[34] Its apparent benefits despite a lack of any
significant antagonistic properties at dopamine receptors or
the 5-HT2A receptor raises interesting questions about the
etiology of psychosis.

Substance use

There is tentative evidence that it may be useful in decreasing

the desired effects of alcohol.[35] There is also some tentative
evidence in those who are addicted to stimulants.[36]

Postanesthetic shivering

Two small, placebo-controlled trials have been conducted to

assess the efficacy of ondansetron for postanesthetic
shivering, a common occurrence after surgery. Ondansetron
was found to be as effective as pethidine (meperidine,
Demerol) when given as a single intravenous dose before
anesthesia.[37]
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External links
U.S. National Library of Medicine: Drug Information Portal –
Ondansetron

Retrieved from "https://en.wikipedia.org/w/index.php?

title=Ondansetron&oldid=890510125"
Last edited 2 months ago by an anonymous user

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