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Revision as of 12:05, 16 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 477126455 of page Ondansetron for the Chem/Drugbox validation project (updated: 'DrugBank').  Latest revision as of 04:14, 22 November 2024 edit Boredintheevening (talk | contribs)Extended confirmed users4,151 edits →Children: Both sentences should be cited, fixedTags: Mobile edit Mobile web edit 
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{{Short description|Medication to prevent nausea and vomiting}}
{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
{{Use dmy dates|date=February 2024}}
{{Drugbox
{{cs1 config|name-list-style=vanc|display-authors=6}}
| Verifiedfields = changed
{{Infobox drug
| verifiedrevid = 458282124
| verifiedrevid = 477170896
| IUPAC_name = (''RS'')-9-methyl-3--2,3-dihydro-1''H''-carbazol-4(9''H'')-one
| image = Ondansetron skeletal.svg | image = Ondansetron skeletal.svg
| width = 200px | width = 225
| alt =
| image2 = Ondansetron 3D.png | image2 = Ondansetron 3D.png
| width2 = 250
| imagename = 1 : 1 mixture (racemate)
| alt2 =
| drug_name = Ondansetron
| caption = <!-- Clinical data -->

| pronounce =
<!--Clinical data-->
| tradename = Zofran | tradename = Zofran, others<ref name="Ondansetron international" />
| Drugs.com = {{drugs.com|monograph|ondansetron-hydrochloride}} | Drugs.com = {{drugs.com|monograph|ondansetron}}
| MedlinePlus = a601209 | MedlinePlus = a601209
| DailyMedID = Ondansetron
| pregnancy_AU = B1 | pregnancy_AU = B1
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Ondansetron Use During Pregnancy | website=Drugs.com | date=3 October 2019 | url=https://www.drugs.com/pregnancy/ondansetron.html | access-date=7 September 2020 | archive-date=18 September 2020 | archive-url=https://web.archive.org/web/20200918212204/https://www.drugs.com/pregnancy/ondansetron.html | url-status=live }}</ref>
| pregnancy_US = B
| pregnancy_category =
| routes_of_administration = ], ], ], ], ]
| class = {{plainlist|
*];
*]}}
| ATC_prefix = A04
| ATC_suffix = AA01
| ATC_supplemental = <!-- Legal status -->
| legal_AU = S4 | legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Zofran Product and Consumer Medicine Information Licence | website=TGA eBS | url=http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01055-1 | access-date=28 August 2022 | archive-date=29 August 2022 | archive-url=https://web.archive.org/web/20220829011623/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01055-1 | url-status=live }}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Zofran Product information | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=43116 | access-date=28 August 2022 | archive-date=29 August 2022 | archive-url=https://web.archive.org/web/20220829011237/https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=43116 | url-status=live }}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM | legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Zofran Tablets 4 mg - Summary of Product Characteristics (SmPC) | website=(emc) | date=19 January 2022 | url=https://www.medicines.org.uk/emc/product/195/smpc | access-date=28 August 2022 | archive-date=29 August 2022 | archive-url=https://web.archive.org/web/20220829011033/https://www.medicines.org.uk/emc/product/195/smpc | url-status=dead }}</ref>
| legal_US = Rx-only | legal_US = Rx-only
| legal_US_comment = <ref name="Zofran FDA label" />
| routes_of_administration = Oral, ], ], ]
| legal_EU = Rx-only
| legal_EU_comment = <ref>{{cite web|url=https://www.ema.europa.eu/documents/psusa/ondansetron-list-nationally-authorised-medicinal-products-psusa/00002217/202102_en.pdf|title=List of nationally authorised medicinal products : Active substance: ondansetron :Procedure no.: PSUSA/00002217/202102|website=Ema.europa.eu|access-date=5 March 2022}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->| bioavailability = ~60%
| bioavailability = ~60% | protein_bound = 70–76%
| metabolism = ] (], ], ])
| protein_bound = 70%-76%
| metabolites =
| metabolism = ] (], ], ])
| onset =
| elimination_half-life = 5.7 hours | elimination_half-life = 5.7 hours
| duration_of_action =
| excretion = ]
| excretion = ]


<!--Identifiers--> <!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|??}}
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 99614-02-5 | CAS_number = 99614-02-5
| ATC_prefix = A04 | CAS_supplemental =
| ATC_suffix = AA01
| PubChem = 4595 | PubChem = 4595
| IUPHAR_ligand = 2290
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00904 | DrugBank = DB00904
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00456 | KEGG = D00456
| ChEBI_Ref =
| ChEBI =
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 46 | ChEMBL = 46
| NIAID_ChemDB =

| PDB_ligand =
<!--Chemical data-->
| synonyms = <!-- Chemical and physical data -->
| C=18 | H=19 | N=3 | O=1
| IUPAC_name = (''RS'')-9-Methyl-3--2,3-dihydro-1''H''-carbazol-4(9''H'')-one
| molecular_weight = 293.4 g/mol
| C = 18
| smiles = O=C3c2c1ccccc1n(c2CCC3Cn4ccnc4C)C
| H = 19
| InChI = 1/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/h3-6,9-10,13H,7-8,11H2,1-2H3
| N = 3
| InChIKey = FELGMEQIXOGIFQ-UHFFFAOYAL
| O = 1
| SMILES = O=C1c2c3ccccc3n(C)c2CCC1Cn4ccnc4C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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/h3-6,9-10,13H,7-8,11H2,1-2H3 | StdInChI = 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/h3-6,9-10,13H,7-8,11H2,1-2H3
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FELGMEQIXOGIFQ-UHFFFAOYSA-N | StdInChIKey = FELGMEQIXOGIFQ-UHFFFAOYSA-N
}} }}

<!-- Definition and medical uses -->
'''Ondansetron''', sold under the brand name '''Zofran''' among others, is a medication used to prevent ] and ] caused by ], ], ], or ].<ref name="AHFS2016" /> It is also effective for treating ].<ref>{{cite journal | vauthors = Schnadower D, Finkelstein Y, Freedman SB | title = Ondansetron and probiotics in the management of pediatric acute gastroenteritis in developed countries | journal = Current Opinion in Gastroenterology | volume = 31 | issue = 1 | pages = 1–6 | date = January 2015 | pmid = 25333367 | doi = 10.1097/mog.0000000000000132 | s2cid = 9334264 }}</ref><ref>{{cite journal | vauthors = Freedman SB, Ali S, Oleszczuk M, Gouin S, Hartling L | title = Treatment of acute gastroenteritis in children: an overview of systematic reviews of interventions commonly used in developed countries | journal = Evidence-Based Child Health | volume = 8 | issue = 4 | pages = 1123–37 | date = July 2013 | pmid = 23877938 | doi = 10.1002/ebch.1932 }}</ref> It can be given ] (by mouth), ] (injection into a muscle), or ] (injection into a vein).<ref name="AHFS2016">{{cite web|title=Ondansetron Hydrochloride|url=https://www.drugs.com/monograph/ondansetron-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|access-date=11 February 2017|archive-url=https://web.archive.org/web/20160503132329/https://www.drugs.com/monograph/ondansetron-hydrochloride.html|archive-date=3 May 2016|url-status=live}}</ref>

<!-- Side effects and mechanism of action -->
Common ]s include ], ], ], ], and ].<ref name=AHFS2016 /> Serious side effects include ] and ].<ref name=AHFS2016 /> It appears to be safe during ] but has not been well studied in this group.<ref name=AHFS2016 /> It is a ] ].<ref name=AHFS2016 /> It does not have any effect on ] or ]s.<ref name=Mil2012>{{cite book| veditors = Miloro M |title=Peterson's principles of oral and maxillofacial surgery.|date=2012|publisher=People's Medical Pub. House-USA|location=Shelton, CT|isbn=978-1-60795-111-7|page=86|edition=3rd|url=https://books.google.com/books?id=Gxo8AwAAQBAJ&pg=PA86|url-status=live|archive-url=https://web.archive.org/web/20160201173938/https://books.google.ca/books?id=Gxo8AwAAQBAJ&pg=PA86|archive-date=1 February 2016}}</ref>

<!-- History, society and culture -->
Ondansetron was patented in 1984 and approved for medical use in 1990.<ref>{{cite book |vauthors=FischerJ, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=448 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA448 |access-date=25 August 2020 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112141709/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA448 |url-status=live }}</ref> It is on the ].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> It is available as a ].<ref name=AHFS2016 /> In 2022, it was the 61st most commonly prescribed medication in the United States, with more than 10{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Ondansetron Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Ondansetron | access-date = 30 August 2024 }}</ref>

==Medical uses==
Ondansetron is ] for the prevention of ] and ].<ref name="Zofran FDA label" /><ref>{{cite web | title=Ondansetron hydrochloride injection | website=DailyMed | date=19 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=59c4227a-90b6-4297-aacd-05bd097010c1 | access-date=8 July 2023 | archive-date=8 July 2023 | archive-url=https://web.archive.org/web/20230708173847/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=59c4227a-90b6-4297-aacd-05bd097010c1 | url-status=live }}</ref>

===Pregnancy===
Ondansetron is used ] to treat ] and ] of ]. It is typically used after other ] drugs have failed.<ref name="Smith, Judith A. 2011">{{cite web | vauthors = Smith JA, Refuerzo JS, Ramin SM | publisher = UpToDate | title = Treatment and outcome of nausea and vomiting of pregnancy | url = https://www.uptodate.com/contents/nausea-and-vomiting-of-pregnancy-treatment-and-outcome | url-status = live | archive-url = https://web.archive.org/web/20131203014208/http://www.uptodate.com/contents/treatment-and-outcome-of-nausea-and-vomiting-of-pregnancy | archive-date = 3 December 2013 }}</ref>

A large multi-center cohort study found no association between ondansetron exposure and fetal risk compared to other antiemetics.<ref>{{cite journal | vauthors = Dormuth CR, Winquist B, Fisher A, et al. | title = Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort | journal = JAMA Netw Open | date = April 2021 | volume = 4 | issue = 4 | pages = e215329 | doi = 10.1001/jamanetworkopen.2021.5329| pmid = 33890993 | pmc = 8065380 | doi-access = free }}</ref>

===Cyclic vomiting syndrome===
Ondansetron is one of several antiemetics used during the vomiting phase of ].<ref name="pmid18371009">{{cite journal | vauthors = Abell TL, Adams KA, Boles RG, Bousvaros A, Chong SK, Fleisher DR, Hasler WL, Hyman PE, Issenman RM, Li BU, Linder SL, Mayer EA, McCallum RW, Olden K, Parkman HP, Rudolph CD, Taché Y, Tarbell S, Vakil N | title = Cyclic vomiting syndrome in adults | journal = Neurogastroenterology and Motility | volume = 20 | issue = 4 | pages = 269–84 | date = April 2008 | pmid = 18371009 | doi = 10.1111/j.1365-2982.2008.01113.x | url = https://deepblue.lib.umich.edu/bitstream/2027.42/72300/1/j.1365-2982.2008.01113.x.pdf | hdl = 2027.42/72300 | s2cid = 8718836 | doi-access = free | access-date = 4 November 2018 | archive-date = 28 August 2021 | archive-url = https://web.archive.org/web/20210828195918/https://deepblue.lib.umich.edu/bitstream/handle/2027.42/72300/j.1365-2982.2008.01113.x.pdf;jsessionid=96361A3B422890FD8DAE4512F0E07713?sequence=1 | url-status = live }}</ref>

===Gastroenteritis===
Trials in emergency department settings support the use of ondansetron to abort vomiting episodes associated with ] and ].<ref name="pmid16625009">{{cite journal | vauthors = Freedman SB, Adler M, Seshadri R, Powell EC | title = Oral ondansetron for gastroenteritis in a pediatric emergency department | journal = The New England Journal of Medicine | volume = 354 | issue = 16 | pages = 1698–705 | date = April 2006 | pmid = 16625009 | doi = 10.1056/NEJMoa055119 | doi-access=free | s2cid = 13712069 }}</ref> A randomized controlled trial using a single dose of oral ondansetron in children with presumably viral gastroenteritis found it to be highly effective in stopping vomiting and increasing the effectiveness of oral rehydration therapy, thereby significantly increasing patient satisfaction. Only 16 of the 123 children treated with ondansetron vomited in the following 6 hours.<ref>{{cite journal | vauthors = Hanif H, Jaffry H, Jamshed F, Amreek F, Kumar N, Hussain W, Rizwan A | title = Oral Ondansetron versus Domperidone for Acute Gastroenteritis Associated Vomiting in Young Children | journal = Cureus | volume = 11 | issue = 9 | pages = e5639 | date = September 2019 | pmid = 31700742 | doi = 10.7759/cureus.5639 | doi-access = free | pmc = 6822884 }}</ref> A retrospective review found that ondansetron was used commonly for vomiting due to gastroenteritis, being administered in over 58% of cases. Its use reduced hospital admissions, but was also associated with higher rates of return visits to the 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.<ref name="pmid20031265">{{cite journal | vauthors = Sturm JJ, Hirsh DA, Schweickert A, Massey R, Simon HK | title = Ondansetron use in the pediatric emergency department and effects on hospitalization and return rates: are we masking alternative diagnoses? | journal = Annals of Emergency Medicine | volume = 55 | issue = 5 | pages = 415–22 | date = May 2010 | pmid = 20031265 | doi = 10.1016/j.annemergmed.2009.11.011 }}</ref>

=== Irritable bowel syndrome (IBS) ===
In a study of patients diagnosed as having IBS with diarrhea (IBS-D), ondansetron showed statistically significant effects on stool consistency, frequency, urgency and bloating, but not on pain scores.<ref>{{cite journal | vauthors = Garsed K, Chernova J, Hastings M, Lam C, Marciani L, Singh G, Henry A, Hall I, Whorwell P, Spiller R | title = A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea | journal = Gut | volume = 63 | issue = 10 | pages = 1617–1625 | date = October 2014 | pmid = 24334242 | doi = 10.1136/gutjnl-2013-305989 | pmc = 4173656 }}</ref> This was confirmed in a later trial and meta-analysis<ref name="pmid36866724">{{cite journal | vauthors = Gunn D, Topan R, Barnard L, Fried R, Holloway I, Brindle R, Corsetti M, Scott M, Farmer A, Kapur K, Sanders D, Eugenicos M, Trudgill N, Whorwell P, Mclaughlin J, Akbar A, Houghton L, Dinning PG, Aziz Q, Ford AC, Farrin AJ, Spiller R | title = Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial | journal = Alimentary Pharmacology & Therapeutics | volume = 57 | issue = 11 | pages = 1258–1271 | date = June 2023 | pmid = 36866724 | doi = 10.1111/apt.17426 | url = }}</ref> and is included in international guidelines.<ref name="pmid35695704">{{cite journal | vauthors = Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, Barboi O, Bodini G, Bor S, Chiarioni G, Cristian G, Corsetti M, Di Sabatino A, Dimitriu AM, Drug V, Dumitrascu DL, Ford AC, Hauser G, Nakov R, Patel N, Pohl D, Sfarti C, Serra J, Simrén M, Suciu A, Tack J, Toruner M, Walters J, Cremon C, Barbara G | title = Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility | journal = United European Gastroenterology Journal | volume = 10 | issue = 6 | pages = 556–584 | date = July 2022 | pmid = 35695704 | pmc = 9278595 | doi = 10.1002/ueg2.12259 | url = }}</ref>

==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.<ref name="Zofran FDA label" />

Three open non-comparative studies have been conducted to assess the safety and efficacy of ondansetron in children receiving a variety of chemotherapy regimens.<ref>{{cite journal | vauthors = Stevens RF | title = The role of ondansetron in paediatric patients: a review of three studies | journal = European Journal of Cancer | volume = 27 | issue = Suppl 1 | pages = S20–S22 | date = 1 January 1991 | pmid = 1831631 | url = https://europepmc.org/article/med/1831631 | access-date = 8 July 2023 | url-status = live | archive-url = https://web.archive.org/web/20230708132048/https://europepmc.org/article/med/1831631 | archive-date = 8 July 2023 }}</ref>

Ondansetron was well tolerated and none of the patients experienced extrapyramidal symptoms.<ref>{{cite journal | vauthors = Stevens RF | title = The role of ondansetron in paediatric patients: a review of three studies | journal = European Journal of Cancer | volume = 27 | issue = Suppl 1 | pages = S20–S22 | date = 1 January 1991 | pmid = 1831631 | url = https://europepmc.org/article/med/1831631 | access-date = 8 July 2023 | url-status = live | archive-url = https://web.archive.org/web/20230708132048/https://europepmc.org/article/med/1831631 | archive-date = 8 July 2023 }}</ref>

==Adverse effects==
] is the most common ].<ref name="Zofran FDA label" /> 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.<ref name="pmid9416710">{{cite journal | vauthors = Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ | title = Efficacy, dose-response, and safety of ondansetron in prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized placebo-controlled trials | journal = Anesthesiology | volume = 87 | issue = 6 | pages = 1277–89 | date = December 1997 | pmid = 9416710 | doi = 10.1097/00000542-199712000-00004 | s2cid = 8049193 | doi-access = free }}</ref>

], ], and ] are other commonly reported side effects. It is broken down by the ] ] system and it has little effect on the ] of other drugs broken down by this system.<ref name="AHFS2016" />

===QT prolongation===
Use of ondansetron has been associated with prolongation of the ], which can lead to a potentially fatal heart rhythm known as '']''. 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 ], ], and/or ]. As such, single doses of injectable ondansetron should not exceed 16&nbsp;mg at one time. (Oral dosing recommendations remain intact, including the recommendation of a single 24&nbsp;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.<ref>{{cite web |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-information-regarding-qt-prolongation-ondansetron-zofran |title=FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran) |website=] |access-date=29 November 2012 |url-status=live |archive-url=https://web.archive.org/web/20121214021055/https://www.fda.gov/Drugs/DrugSafety/ucm310190.htm |archive-date=14 December 2012 }}</ref>

===Overdose===
No specific treatment is available for ondansetron overdose; people are managed with supportive measures. An antidote to ondansetron is not known.<ref name="Zofran FDA label">{{cite web | title=Zofran- ondansetron hydrochloride tablet, film coated | website=DailyMed | date=24 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=555f81bc-4ce0-4f77-b394-b974838c4440 | access-date=7 September 2020 | archive-date=6 August 2020 | archive-url=https://web.archive.org/web/20200806135119/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=555f81bc-4ce0-4f77-b394-b974838c4440 | url-status=live }}</ref>

==Pharmacology==

===Pharmacodynamics===
Ondansetron is a highly ] ] ], with low ] for ]s. The 5-HT<sub>3</sub> receptors are present both ] on ] terminals and centrally in the ] of the ] in the ]. Serotonin is released by the ]s of the ] in response to ]s and may stimulate vagal ]s (via 5-HT<sub>3</sub> receptors) to initiate the ]. It is thought that ondansetron's antiemetic action is mediated mostly via antagonism of vagal afferents with a minor contribution from antagonism of ] receptors.<ref>{{cite journal | vauthors = Browning KN | title = Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology | journal = Frontiers in Neuroscience | volume = 9 | pages = 413 | date = October 2015 | pmid = 26578870 | pmc = 4625078 | doi = 10.3389/fnins.2015.00413 | doi-access = free }}</ref> The ''R''– and ''S''–ondansetron isomers have similar potency as serotonin antagonists when tested on ''ex vivo'' rat ].<ref name="Butler-1988">{{cite journal | vauthors = Butler A, Hill JM, Ireland SJ, Jordan CC, Tyers MB | title = Pharmacological properties of GR38032F, a novel antagonist at 5-HT3 receptors | journal = British Journal of Pharmacology | volume = 94 | issue = 2 | pages = 397–412 | date = June 1988 | pmid = 2969267 | pmc = 1854010 | doi = 10.1111/j.1476-5381.1988.tb11542.x }}</ref> However, the ''R''–ondansetron enantiomer was 7.9 times more potent as an antagonist of serotonin and ] (2-methylserotonin) when tested on the longitudinal ] from guinea pig ]. However, the guinea pig ileum test was likely not as faithful as a test of 5-HT<sub>3</sub> receptor antagonism, because ondansetron only partially blocked the effect of serotonin, while it completely blocked the effect of 2-methylserotonin.<ref name="Butler-1988" />

===Pharmacokinetics===
Ondansetron may have a degree of ] due to binding to ] and efflux out of the brain at the ].<ref name="pmid8647944">{{cite journal | vauthors = Schinkel AH, Wagenaar E, Mol CA, van Deemter L | title = P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs | journal = Journal of Clinical Investigation| volume = 97 | issue = 11 | pages = 2517–24 | date = June 1996 | pmid = 8647944 | pmc = 507337 | doi = 10.1172/JCI118699 | url = }}</ref><ref name="pmid32017606">{{cite journal | vauthors = Kwan C, Bédard D, Frouni I, Gaudette F, Beaudry F, Hamadjida A, Huot P | title = Pharmacokinetic profile of the selective 5-HT3 receptor antagonist ondansetron in the rat: an original study and a minireview of the behavioural pharmacological literature in the rat | journal = Canadian Journal of Physiology and Pharmacology| volume = 98 | issue = 7 | pages = 431–440 | date = July 2020 | pmid = 32017606 | doi = 10.1139/cjpp-2019-0551 | s2cid = 211035717 | url = }}</ref><ref name="pmid16931690">{{cite journal | vauthors = Scott JA, Wood M, Flood P | title = The pronociceptive effect of ondansetron in the setting of P-glycoprotein inhibition | journal = Anesthesia & Analgesia| volume = 103 | issue = 3 | pages = 742–6 | date = September 2006 | pmid = 16931690 | doi = 10.1213/01.ane.0000228861.80314.22 | s2cid = 44405604 | url = | doi-access = free }}</ref> Ondansetron is marketed as a ] mixture of ''R''–(–)–ondansetron and ''S''–(+)–ondansetron, and the two enantiomers have significantly different kinetics. In rats given 2 mg/kg intravenous doses of each enantiomer separately, ''R''–(–)–ondansetron was found to have a 37% longer half-life (''P'' < 0.05) and an 87% higher area-under-curve or AUC (''P'' < 0.01) compared to ''S''–(+)–ondansetron, indicating that the ''R'' enantiomer is metabolized more slowly.<ref name="Duan-2018">{{cite journal | vauthors = Duan M, Zhao Q, Zhong D, Yuan Y | title = Pharmacokinetics of R-(-)ondansetron compared with that of S-(-)ondansetron in rats using an LC-MS/MS method | journal = Biomedical Chromatography | volume = 33 | issue = 3 | pages = e4426 | date = March 2019 | pmid = 30408206 | doi = 10.1002/bmc.4426 }}</ref> The chiral carbon in ondansetron is adjacent to a carbonyl group, so ] ] could theoretically lead to interconversion between the two enantiomers under physiologic conditions, if the hydrogen on the chiral carbon were removed and then replaced with opposite chirality. An experiment in rats given each enantiomer separately showed no evidence of this interconversion, the chirality was stable ''in vivo''.<ref name="Duan-2018" /> A study of 141 human patients given 4 or 8 mg of intravenous ondansetron for the prevention of post-operative nausea and vomiting also found that ''R'' and ''S''–ondansetron have different pharmacokinetic properties. Each patient was classified according to their genotype for the liver enzymes CYP2D6 and CYP3A5, and they were put on a spectrum between poor metabolizers (slow) and ultra metabolizers (fast). CYP2D6 was found to be more important for the elimination of ''S''–ondansetron, whereas CYP3A5 genotype had no impact on ''S''–ondansetron plasma levels, measured 3 hours after drug administration. CYP3A5 was more important for ''R''–ondansetron clearance, and CYP2D6 genotype had no consistent effect on plasma levels of ''R''–ondansetron at 3 hours.<ref name="Stamer-2011">{{cite journal | vauthors = Stamer UM, Lee EH, Rauers NI, Zhang L, Kleine-Brueggeney M, Fimmers R, Stuber F, Musshoff F | title = CYP2D6- and CYP3A-dependent enantioselective plasma concentrations of ondansetron in postanesthesia care | journal = Anesthesia and Analgesia | volume = 113 | issue = 1 | pages = 48–54 | date = July 2011 | pmid = 21596874 | doi = 10.1213/ANE.0b013e31821d01bc }}</ref>

==History==
]

Ondansetron (marketed under the brand name Zofran) was developed in the mid-1980s by ] in London. It was granted U.S. patent protection in September 1987,<ref name="US4695578">{{ cite patent | country = US | number = 4695578 | status =patent | title = 1,2,3,9-tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, composition containing them, and method of using them to treat neuronal 5HT function disturbances | gdate = 22 September 1987 | fdate = 17 November 1986 | inventor = Coates IH, Bell JA, Humber DC, Ewan GB | assign1 = Glaxo Group Limited }}</ref> received a use patent June 1988,<ref name="US4753789">{{ cite patent | country = US | number = 4753789 | status =patent | title = Method for treating nausea and vomiting | gdate = 28 June 1988 | fdate = 24 June 1986 | inventor = Tyers MB, Coates IH, Humber DC, Ewan GB, Bell JA | assign1 = Glaxo Group Limited }}</ref> and was approved by the U.S. ] (FDA) in January 1991. It was granted another divisional patent in November 1996.<ref name="US5578628">{{ cite patent | country = US | number = 5578628 | status =patent | title = Medicaments for the treatment of nausea and vomiting | gdate = 26 November 1996 | fdate = 30 March 1990 | inventor = Tyers MB, Coates IH, Humber DC, Ewan GB, Bell JA | assign1 = Glaxo Group Limited }}</ref> Finally, owing to GlaxoSmithKline's research on pediatric use, ondansetron's patent protection was extended until December 2006.<ref name="url_fda_pe">{{cite web | url = https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_06_03_OndansetronUseReview%20Cleared.pdf | title = One Year Post-Pediatric Exclusivity Post-marketing Adverse Event Review: Drug Use Data Zofran | date = 7 March 2006 | work = Memorandum | publisher = U.S. Food and Drug Administration | url-status = live | archive-url = https://web.archive.org/web/20150924170611/https://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_06_03_OndansetronUseReview%20Cleared.pdf | archive-date = 24 September 2015 }}</ref> 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).<ref>IHS. (2006). Generics firms line up to enter Zofran market. Retrieved from {{cite web |url=https://ihsmarkit.com/country-industry-forecasting.html?id=106598562 |title=Generics Firms Line Up to Enter Zofran Market |access-date=20 January 2014 |url-status=live |archive-url=https://web.archive.org/web/20140201231754/http://www.ihs.com/products/global-insight/industry-economic-report.aspx?id=106598562 |archive-date=1 February 2014 }}</ref> The first generic versions were approved by the U.S. FDA in December 2006, with marketing approval granted to ] and SICOR Pharmaceuticals.<ref name="urlFDA Approves First Generic Ondansetron Tablets, Orally Disintegrating Tablets and Oral Solution">{{cite press release | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108817.htm | title = FDA Approves First Generic Ondansetron Tablets, Orally Disintegrating Tablets and Oral Solution | date = 17 December 2006 | publisher = U.S. Food and Drug Administration | url-status = dead | archive-url = https://web.archive.org/web/20140618211006/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2006/ucm108817.htm | archive-date = 18 June 2014 }}</ref>

In December 2012, the FDA announced that the 32{{nbsp}}mg, single intravenous (IV) dose of ondansetron was being withdrawn from U.S. market because of the potential for serious cardiac issues from prolonged QT interval.<ref>{{cite web |title=FDA Drug Safety Communication: Updated information on 32 mg intravenous ondansetron (Zofran) dose and pre-mixed ondansetron products |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-32-mg-intravenous-ondansetron-zofran-dose-and-pre |website=U.S. ] (FDA) |access-date=12 December 2012 |archive-date=13 December 2019 |archive-url=https://web.archive.org/web/20191213203539/https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-32-mg-intravenous-ondansetron-zofran-dose-and-pre |url-status=live }}</ref>

In 2018, ] and Biolab were granted a patent for an ] form of the drug.<ref>{{Cite web|title=Sabia que um remédio para enjoo traz 90% dos royalties que a USP recebe? - Agência USP de Inovação|url=http://www.inovacao.usp.br/sabia-que-um-remedio-para-enjoo-traz-90-dos-royalties-que-a-usp-recebe/|access-date=6 October 2020|language=pt-BR}}</ref>

==Society and culture==

===Publication bias===
In 1997, ondansetron was the subject of a ] case study. Researchers examined 84 trials, with 11,980 people receiving ondansetron, published between 1991 and September 1996. Intravenous ondansetron 4&nbsp;mg versus placebo was investigated in 16 reports and three further reports which had been duplicated a total of six times. The ] (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.<ref name=Tramer>{{cite journal | vauthors = Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ | title = Impact of covert duplicate publication on meta-analysis: a case study | journal = BMJ | volume = 315 | issue = 7109 | pages = 635–40 | date = September 1997 | pmid = 9310564 | pmc = 2127450 | doi = 10.1136/bmj.315.7109.635 }}</ref>

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.<ref name=Tramer /> Their analysis was a subject of an editorial in the '']'' in 1999.<ref name=Rennie>{{cite journal | vauthors = Rennie D | title = Fair conduct and fair reporting of clinical trials | journal = JAMA | volume = 282 | issue = 18 | pages = 1766–8 | date = November 1999 | pmid = 10568651 | doi = 10.1001/jama.282.18.1766 }}</ref>

===Availability===
Ondansetron is a ] and is available in many countries under many brand names.<ref name="Ondansetron international">{{cite web | title=Ondansetron international | website=Drugs.com | date=2 September 2020 | url=https://www.drugs.com/international/ondansetron.html | access-date=2 February 2014 | archive-url=https://web.archive.org/web/20140221202123/https://www.drugs.com/international/ondansetron.html |archive-date=21 February 2014 |url-status=live }}</ref>

==References==
{{Reflist}}

{{5-HT3 antagonists}}
{{Serotonin receptor modulators}}
{{GlaxoSmithKline}}
{{Portal bar | Medicine}}
{{Authority control}}

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