Ondansetron
Meta-analyses found ondansetron cut vomiting after surgery by about 45% against placebo, and in children with stomach bugs it raised the share who stopped vomiting and lowered the need for IV fluids. One small trial found it eased pregnancy nausea. Headache and constipation were common. The label warns of QT prolongation, and pregnancy studies were inconsistent on oral clefts.
Add to Bio HackChecked 2026-11-13
- Status
- Prescription drug in the US. FDA-approved to prevent nausea and vomiting from moderately and highly emetogenic cancer chemotherapy, from abdominal or total body radiotherapy, and after surgery. Use for stomach bugs in children, nausea in pregnancy and irritable bowel syndrome with diarrhea is off-label.
- Also called
- ondansetron, Zofran, Zofran ODT, Zuplenz, 5-HT3 antagonist, anti-nausea medicine
- Taken for
- nausea, vomiting, stomach bug, gastroenteritis, morning sickness, nausea in pregnancy, chemotherapy nausea, nausea after surgery, irritable bowel syndrome with diarrhea
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help6
- StrongShown to lower vomiting in the 24 hours after surgery by about 45% against placebo, though several other antiemetics and combinations ranked higher.
- StrongShown to raise the share of children who stopped vomiting and to cut the need for IV fluids by about half against placebo in children with gastroenteritis.
- ModerateShown to prevent vomiting with chemotherapy in controlled trials, with no vomiting over 3 days in 61% on ondansetron against 6% on placebo in one trial.
- ModerateShown to firm stools and reduce diarrhea symptoms against placebo in pooled trials, with about 5 treated for one extra stool responder, but not to relieve abdominal pain.
- LimitedSmall trials found ondansetron prevented vomiting from radiotherapy better than placebo, metoclopramide and prochlorperazine.
- LimitedOne small trial in pregnancy found ondansetron eased nausea more than doxylamine with pyridoxine over 5 days.
Reported risks10
- StrongShown to raise headache against placebo, in 24% against 13% with chemotherapy and 9% against 5% after surgery.Very common
- ModerateShown to raise fatigue and constipation against placebo in chemotherapy trials, with fatigue in 13% against 2% and constipation in 9% against under 1%.Very common
- LimitedThe label reports ALT or AST above twice the upper limit in 1% to 2% of patients on ondansetron with chemotherapy, transient, with chemotherapy's role unclear.Common
- ModerateMixed results: one large cohort and a meta-analysis linked first-trimester use to a small rise in oral clefts, about 3 more per 10,000 births, with no rise in overall malformations.Uncommon
- LimitedThe label warns ondansetron prolongs the QT interval, by 19.5 milliseconds at 32 mg intravenously and 5.6 at 8 mg, with postmarketing reports of torsade de pointes.How often is not known
- LimitedThe label reports serotonin syndrome with ondansetron, mostly with other serotonergic drugs such as SSRIs and SNRIs, some cases fatal. It gives no rate.How often is not known
- LimitedThe label warns ondansetron can mask a worsening ileus or stomach distension after abdominal surgery or chemotherapy. It gives no rate.How often is not known
- LimitedThe label reports heart muscle ischemia after ondansetron, mostly with intravenous use and often from coronary artery spasm. It gives no rate.How often is not known
- LimitedThe label reports anaphylaxis and bronchospasm, including in people allergic to other drugs of the same class. It gives no rate.How often is not known
- LimitedThe label lists apomorphine as a contraindication because of profound low blood pressure and loss of consciousness, and notes tramadol may work less well alongside ondansetron.How often is not known
What people take it for, and what was found
Shown to help6
Nausea and vomiting after surgery
Shown to lower vomiting in the 24 hours after surgery by about 45% against placebo, though several other antiemetics and combinations ranked higher.
Compared with placebo [1][2][3]; dexamethasone, droperidol, granisetron, aprepitant and drug combinations, in network comparisons [1]
The numbers and sources
- Effect
- In a network meta-analysis, ondansetron reduced vomiting within 24 hours against placebo (RR 0.55, 95% CI 0.51 to 0.60, high certainty), ranking 13th of 28 single drugs. Combinations of drugs generally reduced vomiting more [1]. An earlier Cochrane review found eight drugs, ondansetron among them, prevented postoperative nausea and vomiting with relative risks of 0.60 to 0.80, and estimated that where 80 of 100 people would be sick, about 28 benefit from a drug [2]. In two label trials in women, a single 16 mg dose before anesthesia reduced nausea and vomiting more than placebo [3].
- Population
- 97,516 adults in 585 studies, 246 of them of ondansetron [1]; 103,237 people in 737 studies [2]; 865 women having inpatient surgery [3].
- Sources
- [1], [2], [3]
- Caveats
- Most studies were small and 83% of participants were women [1]. The label states no trials of the tablet were done in men [3]. Low doses showed no clinically important benefit [1].
Nausea and vomiting with chemotherapy
Shown to prevent vomiting with chemotherapy in controlled trials, with no vomiting over 3 days in 61% on ondansetron against 6% on placebo in one trial.
Compared with placebo [3]; a historical placebo group [3]
The numbers and sources
- Effect
- In a placebo-controlled trial with a cyclophosphamide and doxorubicin regimen, 61% on ondansetron 8 mg had no vomiting over 3 days, against 6% on placebo, and 21% against 71% had more than 2 episodes or withdrew. With cisplatin regimens, 66% on a single 24 mg dose had no vomiting and no rescue medicine over 24 hours, better than a historical placebo group in which more than 90% vomited [3].
- Population
- 67 adults in the placebo-controlled trial and 357 adults in the cisplatin trial, as reported in the label [3].
- Sources
- [3]
- Caveats
- The cisplatin trials compared with a historical control, not a concurrent placebo group [3].
Nausea and vomiting with radiotherapy
Small trials found ondansetron prevented vomiting from radiotherapy better than placebo, metoclopramide and prochlorperazine.
Compared with placebo, metoclopramide and prochlorperazine [3]
The numbers and sources
- Effect
- Ondansetron 8 mg prevented vomiting from total body irradiation more than placebo, and gave more complete control of vomiting than metoclopramide with single high-dose abdominal radiotherapy and than prochlorperazine with daily fractionated abdominal radiotherapy [3].
- Population
- 20, 105 and 135 patients in three trials, as reported in the label [3].
- Sources
- [3]
- Caveats
- The label gives no rates for these trials, and the placebo-controlled trial had 20 patients [3].
Vomiting in children with stomach bugs
Shown to raise the share of children who stopped vomiting and to cut the need for IV fluids by about half against placebo in children with gastroenteritis.
Compared with placebo [4][5][6]
The numbers and sources
- Effect
- Oral ondansetron raised the share who stopped vomiting (RR 1.34, NNT 5), and lowered IV rehydration in the emergency department (RR 0.41, NNT 5) and immediate hospital admission (RR 0.40, NNT 17) [4]. A later review found fewer oral rehydration failures (RR 0.5, 95% CI 0.37 to 0.69), less IV rehydration (RR 0.45, 95% CI 0.31 to 0.63) and fewer admissions (RR 0.53, 95% CI 0.29 to 0.97), with no difference in vomiting cessation after 4, 24 or 48 hours [5]. A single dose lowered oral rehydration failure (RR 0.43, 95% CI 0.34 to 0.55), IV hydration (RR 0.44, 95% CI 0.34 to 0.57) and hospitalization within 8 hours (RR 0.49, 95% CI 0.32 to 0.75) [6].
- Population
- 1,020 children in seven trials [4]; 1,215 children in 10 trials [5]; 2,146 children and adolescents in 13 trials [6].
- Sources
- [4], [5], [6]
- Caveats
- Return visits to the emergency department did not differ (RR 1.14) [5][6]. Diarrhea was reported as a side effect in four of five ondansetron studies [4].
Nausea and vomiting in pregnancy
One small trial in pregnancy found ondansetron eased nausea more than doxylamine with pyridoxine over 5 days.
Compared with doxylamine with pyridoxine [7]
The numbers and sources
- Effect
- Median nausea scores fell 51 mm on a 100 mm scale on ondansetron 4 mg against 20 mm on doxylamine with pyridoxine, and vomiting scores fell 41 against 17 mm. Sedation and constipation did not differ [7].
- Population
- 36 pregnant women with nausea and vomiting, 30 completing follow-up [7].
- Sources
- [7]
- Caveats
- A very small trial with uneven follow-up (72% and 94%) and no placebo group [7]. Use in pregnancy is off-label.
Irritable bowel syndrome with diarrhea
Shown to firm stools and reduce diarrhea symptoms against placebo in pooled trials, with about 5 treated for one extra stool responder, but not to relieve abdominal pain.
Compared with placebo [8]
The numbers and sources
- Effect
- In the TRITON trial, 40.5% on ondansetron and 27.9% on placebo met the FDA composite endpoint, a difference that was not significant, while stool consistency improved (adjusted mean difference -0.7). Pooled with two similar trials, ondansetron improved the composite endpoint (RR of not responding 0.86, 95% CI 0.75 to 0.98, NNT 9) and stool response (RR 0.65, 95% CI 0.52 to 0.82, NNT 5), but not abdominal pain response (RR 0.95, 95% CI 0.74 to 1.20) [8].
- Population
- 80 adults in TRITON over 12 weeks, and 327 in the pooled analysis of three trials [8].
- Sources
- [8]
- Caveats
- TRITON recruited 80 of a planned 400 patients [8].
Doses studied
The label lists a single 24 mg dose before highly emetogenic chemotherapy, 8 mg twice a day for moderately emetogenic chemotherapy, 8 mg before radiotherapy, and 16 mg one hour before anesthesia for surgery. For children aged 4 to 11 having chemotherapy it lists 4 mg three times a day [3]. The pregnancy trial used 4 mg [7]. TRITON started at 4 mg once a day and allowed titration up to 8 mg three times a day [8].
Risks
Reported risks9
Headache
Shown to raise headache against placebo, in 24% against 13% with chemotherapy and 9% against 5% after surgery.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Headache occurred in 24% on ondansetron 8 mg twice daily and 13% on placebo in chemotherapy trials, in 11% on a single 24 mg dose with cisplatin, and in 9% against 5% in surgery trials [3]. In a Cochrane review of drugs for postoperative nausea, headache was more common after ondansetron (RR 1.16) [2].
- Population
- 242 adults on ondansetron and 262 on placebo with chemotherapy, 550 and 531 having surgery [3]; 737 studies [2].
- Sources
- [3], [2]
- Caveats
- The label notes a causal link was unclear for many reactions because patients took several drugs [3].
Fatigue, constipation and diarrhea
Shown to raise fatigue and constipation against placebo in chemotherapy trials, with fatigue in 13% against 2% and constipation in 9% against under 1%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In chemotherapy trials, malaise or fatigue occurred in 13% on ondansetron and 2% on placebo, constipation in 9% and under 1%, and diarrhea in 6% and 4%. Extrapyramidal reactions occurred in under 1% [3]. The label states repeated dosing slowed colonic transit in healthy people [3].
- Population
- 242 adults on ondansetron and 262 on placebo [3].
- Sources
- [3]
- Caveats
- Patients were also receiving chemotherapy, which causes some of these effects.
Raised liver enzymes
The label reports ALT or AST above twice the upper limit in 1% to 2% of patients on ondansetron with chemotherapy, transient, with chemotherapy's role unclear.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- AST or ALT exceeded twice the upper limit of normal in about 1% to 2% of 723 patients receiving ondansetron with cyclophosphamide-based chemotherapy. The rises were transient and not related to dose or duration, and symptomatic liver disease did not occur. Liver failure and death have been reported in cancer patients also taking liver-toxic drugs [3].
- Population
- 723 patients in US chemotherapy trials [3].
- Sources
- [3]
- Caveats
- No placebo rate is given, and the label states the role of chemotherapy is unclear [3].
QT prolongation and abnormal heart rhythm
The label warns ondansetron prolongs the QT interval, by 19.5 milliseconds at 32 mg intravenously and 5.6 at 8 mg, with postmarketing reports of torsade de pointes.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In a placebo-controlled crossover study, the maximum mean increase in corrected QT was 19.5 milliseconds after 32 mg intravenously and 5.6 milliseconds after 8 mg, with a predicted 14.0 milliseconds at 24 mg and 9.1 at 16 mg. Postmarketing cases of torsade de pointes have been reported. The label calls for avoiding it in congenital long QT syndrome and for ECG monitoring with low potassium or magnesium, heart failure, slow heart rhythms or other QT-prolonging drugs [3].
- Population
- 58 healthy adults in a QT study, and postmarketing reports [3].
- Sources
- [3]
- Caveats
- The QT study used intravenous doses. The 8 mg dose did not prolong QT to a clinically relevant extent [3].
Serotonin syndrome
The label reports serotonin syndrome with ondansetron, mostly with other serotonergic drugs such as SSRIs and SNRIs, some cases fatal. It gives no rate.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Serotonin syndrome has been reported with 5-HT3 antagonists alone, and most reports involved SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol or intravenous methylene blue. Some cases were fatal, and most occurred in a recovery room or infusion center. Cases have also followed ondansetron overdose alone [3].
- Population
- Postmarketing reports [3].
- Sources
- [3]
- Caveats
- Reports, with no denominator.
Masking of bowel blockage
The label warns ondansetron can mask a worsening ileus or stomach distension after abdominal surgery or chemotherapy. It gives no rate.
The numbers and sources
Heart muscle ischemia
The label reports heart muscle ischemia after ondansetron, mostly with intravenous use and often from coronary artery spasm. It gives no rate.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Myocardial ischemia has been reported, in some cases immediately after intravenous administration, resolving with prompt treatment. Coronary artery spasm appears to be the most common cause [3].
- Population
- Postmarketing reports [3].
- Sources
- [3]
- Caveats
- Reports, with no denominator.
Allergic reactions
The label reports anaphylaxis and bronchospasm, including in people allergic to other drugs of the same class. It gives no rate.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported, including in people who had reacted to other 5-HT3 antagonists [3].
- Population
- Reports summarized in the label [3].
- Sources
- [3]
- Caveats
- Reports, with no denominator.
Apomorphine and other interactions
The label lists apomorphine as a contraindication because of profound low blood pressure and loss of consciousness, and notes tramadol may work less well alongside ondansetron.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Use with apomorphine is contraindicated because of the risk of profound hypotension and loss of consciousness. Phenytoin, carbamazepine and rifampin raised ondansetron clearance and lowered its blood levels, with no dose change advised. In two small trials, people given ondansetron used more patient-controlled tramadol [3].
- Population
- Labeling statements and small trials [3].
- Sources
- [3]
- Caveats
- No rates are given.
Mixed results1
Birth defects after use in pregnancy
Mixed results: one large cohort and a meta-analysis linked first-trimester use to a small rise in oral clefts, about 3 more per 10,000 births, with no rise in overall malformations.
The numbers and sources
- How common
- Uncommon: between 1 in 1,000 and 1 in 100 people.
- Effect
- Among 88,467 pregnancies exposed in the first trimester, oral clefts occurred in 14.0 per 10,000 births against 11.1 unexposed (adjusted RR 1.24, 95% CI 1.03 to 1.48, about 2.7 more per 10,000). Cardiac malformations (RR 0.99) and all malformations (RR 1.01) did not rise [9]. A meta-analysis of 12 studies found small rises in ventricular septal defects (OR 1.11, 95% CI 1.00 to 1.23) and oral clefts (OR 1.22, 95% CI 1.00 to 1.49), and none in major malformations overall [10]. The label describes the published findings as inconsistent, with cardiac defect relative risks from 0.97 to 1.62 and conflicting results for cleft palate [3].
- Population
- 1,816,414 pregnancies in US Medicaid data [9]; 12 cohort and case-control studies [10].
- Sources
- [9], [10], [3]
- Caveats
- Observational. The label notes uncertainty over whether prescriptions were taken, and other unadjusted confounders [3].
Claims tested and not found
- That ondansetron reduces return visits for children with stomach bugs. Return visits to the emergency department did not differ from placebo in two meta-analyses (RR 1.14 in each) [5][6].
- That ondansetron relieves pain in irritable bowel syndrome. Across three trials, abdominal pain response did not differ from placebo (RR 0.95, 95% CI 0.74 to 1.20) [8].
Related
Sources
- Weibel S, Rücker G, Eberhart LH, et al. Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: a network meta-analysis. Cochrane Database of Systematic Reviews. 2020. https://doi.org/10.1002/14651858.CD012859.pub2
- Carlisle J, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database of Systematic Reviews. 2006. https://doi.org/10.1002/14651858.CD004125.pub2
- U.S. Food and Drug Administration. Ondansetron hydrochloride tablets, prescribing information (Aurobindo Pharma). 2025. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57578387-1918-4e56-a564-f14fb22340bf
- Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic Reviews. 2011. https://doi.org/10.1002/14651858.CD005506.pub5
- Tomasik E, Ziółkowska E, Kołodziej M, et al. Systematic review with meta-analysis: ondansetron for vomiting in children with acute gastroenteritis. Alimentary Pharmacology & Therapeutics. 2016. https://doi.org/10.1111/apt.13728
- Fugetto F, Filice E, Biagi C, et al. Single-dose of ondansetron for vomiting in children and adolescents with acute gastroenteritis: an updated systematic review and meta-analysis. European Journal of Pediatrics. 2020. https://doi.org/10.1007/s00431-020-03653-0
- Oliveira LG, Capp SM, You WB, et al. Ondansetron Compared With Doxylamine and Pyridoxine for Treatment of Nausea in Pregnancy: A Randomized Controlled Trial. Obstetrics & Gynecology. 2014. https://doi.org/10.1097/AOG.0000000000000479
- Gunn D, Topan R, Barnard L, et al. Randomised, placebo-controlled trial and meta-analysis show benefit of ondansetron for irritable bowel syndrome with diarrhoea: The TRITON trial. Alimentary Pharmacology & Therapeutics. 2023. https://doi.org/10.1111/apt.17426
- Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018. https://doi.org/10.1001/jama.2018.18307
- Picot C, Berard A, Grenet G, et al. Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis. Birth Defects Research. 2020. https://doi.org/10.1002/bdr2.1705