Ondansetron

5-HT3 serotonin receptor antagonist

ATC code: A04AA01

Updated 26 May 2026 · Methodology

Indications

Chemotherapy-induced nausea and vomiting

First line

Standard prophylaxis for acute nausea and vomiting with moderately and highly emetogenic chemotherapy per MASCC/ESMO 2023 and NCCN 2024. For highly emetogenic regimens (cisplatin, AC), ondansetron 8–16 mg IV 30 minutes before chemo is part of a quadruple combination with NK1 antagonist, dexamethasone, and olanzapine. For moderately emetogenic regimens: ondansetron + dexamethasone ± NK1.

Sources

ICD-10: R11.0 · ICD-11: MD90

Postoperative nausea and vomiting

First line

Prevention and treatment of postoperative nausea and vomiting in high-risk patients (female sex, non-smoker, history of PONV or motion sickness). Standard dose 4 mg IV 30 minutes before surgery ends. In patients at risk of recurrence, repeat the dose or combine with dexamethasone and/or droperidol.

Sources

ICD-10: R11 · ICD-11: MD90

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Stress and anxiety

Not recommended

Ondansetron is a serotonin 5-HT3 receptor antagonist. It is prescribed for nausea and vomiting from chemotherapy or radiotherapy, postoperative nausea, and acute gastroenteritis in children (ASCO 2024 and 2018 guidelines). For stress nausea or anxiety vomiting, ondansetron is not used: no clinical studies of such use exist. The drug carries a risk of dose-dependent QT-interval prolongation and Torsades de pointes ( warning, 2012; doses above 16 mg IV are not recommended). If nausea is anxiety-related, other approaches work: breathing techniques, psychotherapy, and, when indicated, treatment of an anxiety disorder. If ondansetron was prescribed for nervous nausea, consider seeking a second opinion.

Sources

ICD-10: F41.9 · ICD-11: 6B0Z

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A selective 5-HT3 receptor antagonist in the area postrema of the medulla and in vagal afferents of the gut. Blocks the emetic reflex triggered by serotonin release from enterochromaffin cells in response to cytotoxics, radiotherapy, and surgery. Metabolized by CYP3A4, CYP2D6, and CYP1A2.

Safety

Contraindications

Hypersensitivity to ondansetron or other 5-HT3 antagonists
Concurrent apomorphine
Congenital long-QT syndrome

Serious adverse effects

QT prolongation and ventricular arrhythmias (including torsades de pointes)
Serotonin syndrome with concomitant SSRIs
Anaphylaxis
Bowel obstruction

Common adverse effects

Headache
Constipation
Warmth or flushing
Elevated liver enzymes

Pregnancy: can you take Ondansetron?

A 2013 Danish cohort study described a small rise in cleft and cardiac defect risk in T1, but later larger studies (Swedish 2014, Canadian 2018) did not confirm the association. Acceptable in severe hyperemesis gravidarum when alternatives (doxylamine + pyridoxine, metoclopramide) are ineffective.

Breastfeeding: can you take Ondansetron?

Limited data. Milk concentrations are low; infant risk with single doses is minimal.

RID, infant dose via milk: 3.7%

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

For CINV, give the first dose 30 minutes before chemotherapy; oral dose 8 mg 1–2 hours before the session. Delayed-phase coverage (days 2–5) uses combinations with an NK1 antagonist and dexamethasone. With QT-prolonging drugs (SSRIs, fluoxetine, methadone, antipsychotics), monitor the ECG.

Drug–drug interactions

5 pairs found. Sorted from critical to minor.

CriticalCitalopramSSRI (selective serotonin reuptake inhibitor)

Mechanism

Ondansetron prolongs QT in a dose-dependent way, as its SmPC states, and the same label describes serotonin syndrome when it is given with SSRIs. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope, with torsade at the far end. Serotonin syndrome is tracked separately: agitation, confusion, tremor, myoclonus, sweating, hyperthermia. Arrhythmia risk is higher with hypokalaemia, hypomagnesaemia and bradycardia.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A single intravenous dose is capped at 16 mg in the label precisely because of QT. Post-operative and chemotherapy nausea have antiemetics outside the setron group, and on citalopram those are the ones chosen.

Sources

Pair details →Citalopram →

CriticalPimavanserinAtypical antipsychotic, selective 5-HT2A inverse agonist

Mechanism

Both drugs prolong QT (pimavanserin 5-8 ms, ondansetron 10-15 ms). Additive – torsades risk.

Symptoms

Syncope, torsades de pointes in patients with additional risk factors.

Management

Combination contraindicated. Use metoclopramide for nausea.

Sources

FDA: Nuplazid (pimavanserin) prescribing information (2023)

Pair details →Pimavanserin →

MajorAmiodaroneClass III antiarrhythmics (Vaughan Williams)

Mechanism

Ondansetron prolongs QT 10-15 ms, amiodarone 30-50 ms. Additive torsades risk.

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Alternative – metoclopramide. If ondansetron needed – single IV dose no higher than 8 mg.

Sources

Pair details →Amiodarone →

MajorDroperidolFirst-generation antipsychotic, butyrophenone. Used as antiemetic.

Mechanism

Additive QT prolongation (ondansetron 10-15 ms + droperidol 10-20 ms).

Symptoms

QTc above 500 ms, syncope, torsades de pointes risk.

Management

Choose one antiemetic or use ECG monitoring.

Sources

FDA: Inapsine (droperidol) prescribing information (2007)

Pair details →Droperidol →

MajorVenlafaxineSNRI (serotonin-norepinephrine reuptake inhibitor)

Mechanism

Venlafaxine blocks the reuptake of serotonin and noradrenaline, and ondansetron blocks serotonin type 3 (5-HT3) receptors. Serotonin syndrome has occurred when ondansetron was given with serotonin and noradrenaline reuptake inhibitors, the antidepressant group that includes venlafaxine (ondansetron SmPC). Ondansetron also prolongs the QT interval in a dose-dependent way. Post-marketing reports with venlafaxine describe QT prolongation and ventricular arrhythmias, mostly in overdose or with other risk factors, so the cardiac effects of the two drugs add up (both SmPCs). Levels of both drugs barely change, because ondansetron does not induce or inhibit the metabolism of other drugs and several liver enzymes clear it (ondansetron SmPC).

Symptoms

Most reports of serotonin syndrome with ondansetron come from post-anaesthesia care units and infusion centres (US Food and Drug Administration, , ondansetron label). Signs include agitation, confusion, hallucinations, sweating, fever, fast heart rate, swings in blood pressure, tremor, muscle twitching and stiffness, overactive reflexes, nausea, vomiting and diarrhoea. QT prolongation itself causes no symptoms and shows only on an electrocardiogram. If torsade de pointes develops, it causes palpitations, dizziness or fainting.

Management

Avoid combining venlafaxine with drugs that prolong the QT interval (venlafaxine SmPC). Ondansetron prolongs QT in a dose-dependent way (ondansetron SmPC). If the patient still needs ondansetron, correct low potassium and magnesium before dosing and do not give a single intravenous dose above 16 mg (ondansetron SmPC). Monitor the electrocardiogram in patients taking other QT-prolonging drugs or with electrolyte abnormalities, heart failure or bradyarrhythmias (ondansetron label, US Food and Drug Administration, ). Warn the patient about serotonin syndrome and watch closely for it, especially at the start of the combination and after a venlafaxine dose increase (venlafaxine and ondansetron labels). If symptoms appear, stop ondansetron and start supportive treatment (ondansetron FDA label).

Sources

Pair details →Venlafaxine →

Label mentions27 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

ModerateAmiodarone
«intervalo QT. El uso simultáneo de ondansetrón con fármacos cardiotóxicos (p. ej., antraciclinas como doxorubicina, daunorubicina o trastuzimab), antibióticos (como eritromicina), antifúngicos (como…»
AEMPS, section 4.5 · Open on CIMA
Moderateantiarrítmicosclass named in the label
«Ondansetron prolonga el intervalo QT de forma dosis dependiente. Además, se han dado casos de post-comercialización de Torsade de Pointes en pacientes tratados con ondansetrón. Evitar ondansetrón en…»
AEMPS, section 4.4 · Open on CIMA
Moderateantineoplásicosclass named in the label
«En la población pediátrica que recibe ondansetrón y quimioterapia hepatotóxica se vigilará estrechamente el posible deterioro de la función hepática.»
AEMPS, section 4.4 · Open on CIMA
ModerateISRSclass named in the label
«Se han observado informes post-comercialización que describen pacientes con síndrome serotoninérgico (incluyendo alteración del estado mental, inestabilidad autonómica y anomalías neuromusculares)…»
AEMPS, section 4.4 · Open on CIMA
Moderatemedicamentos serotoninérgicosclass named in the label
«Se han observado informes post-comercialización que describen pacientes con síndrome serotoninérgico (incluyendo alteración del estado mental, inestabilidad autonómica y anomalías neuromusculares)…»
AEMPS, section 4.4 · Open on CIMA
Moderateserotonergic drugsclass named in the label
«Serotonergic Drugs: Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor…»
FDA, section 7 · Open on DailyMed
ModerateSSRIs/SNRIsclass named in the label
«Serotonergic Drugs: Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor…»
FDA, section 7 · Open on DailyMed
ModerateTramadol
«Tramadol: Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small trials indicate that when used together, ondansetron may increase…»
FDA, section 7 · Open on DailyMed
antiácidosclass named in the label
«La absorción del ondansetrón administrado por vía oral no se ve afectada por los antiácidos.»
AEMPS, section 4.5 · Open on CIMA
antineoplasticsclass named in the label
«Chemotherapy: Carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.»
FDA, section 7 · Open on DailyMed
Atenolol
«intervalo QT. El uso simultáneo de ondansetrón con fármacos cardiotóxicos (p. ej., antraciclinas como doxorubicina, daunorubicina o trastuzimab), antibióticos (como eritromicina), antifúngicos (como…»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«Fenitoína, carbamazepina y rifampicina: En los pacientes tratados con inductores potentes del CYP3A4 (p. ej., fenitoína, carbamazepina y rifampicina), el aclaramiento oral de ondansetrón aumentó y…»
AEMPS, section 4.5 · Open on CIMA
Carbamazepine
«Drugs Affecting Cytochrome P-450 Enzymes: Ondansetron does not itself appear to induce or inhibit the cytochrome P‑450 drug‑metabolizing enzyme system of the liver [see Clinical Pharmacology ( 12.3…»
FDA, section 7 · Open on DailyMed
Erythromycin
«intervalo QT. El uso simultáneo de ondansetrón con fármacos cardiotóxicos (p. ej., antraciclinas como doxorubicina, daunorubicina o trastuzimab), antibióticos (como eritromicina), antifúngicos (como…»
AEMPS, section 4.5 · Open on CIMA
inductores del CYP3A4class named in the label
«Fenitoína, carbamazepina y rifampicina: En los pacientes tratados con inductores potentes del CYP3A4 (p. ej., fenitoína, carbamazepina y rifampicina), el aclaramiento oral de ondansetrón aumentó y…»
AEMPS, section 4.5 · Open on CIMA
Ketoconazole
«intervalo QT. El uso simultáneo de ondansetrón con fármacos cardiotóxicos (p. ej., antraciclinas como doxorubicina, daunorubicina o trastuzimab), antibióticos (como eritromicina), antifúngicos (como…»
AEMPS, section 4.5 · Open on CIMA
Methotrexate
«Chemotherapy: In a crossover trial in 76 pediatric patients, intravenous ondansetron did not increase systemic concentrations of high-dose methotrexate.»
FDA, section 7 · Open on DailyMed
neuromuscular blockersclass named in the label
«Alfentanil and Atracurium: Ondansetron does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with…»
FDA, section 7 · Open on DailyMed
Phenytoin
«Fenitoína, carbamazepina y rifampicina: En los pacientes tratados con inductores potentes del CYP3A4 (p. ej., fenitoína, carbamazepina y rifampicina), el aclaramiento oral de ondansetrón aumentó y…»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«Drugs Affecting Cytochrome P-450 Enzymes: Ondansetron does not itself appear to induce or inhibit the cytochrome P‑450 drug‑metabolizing enzyme system of the liver [see Clinical Pharmacology ( 12.3…»
FDA, section 7 · Open on DailyMed
Rifampicin
«Fenitoína, carbamazepina y rifampicina: En los pacientes tratados con inductores potentes del CYP3A4 (p. ej., fenitoína, carbamazepina y rifampicina), el aclaramiento oral de ondansetrón aumentó y…»
AEMPS, section 4.5 · Open on CIMA
Timolol
«intervalo QT. El uso simultáneo de ondansetrón con fármacos cardiotóxicos (p. ej., antraciclinas como doxorubicina, daunorubicina o trastuzimab), antibióticos (como eritromicina), antifúngicos (como…»
AEMPS, section 4.5 · Open on CIMA
Tramadol
«No hay datos que indiquen que ondansetrón induce o inhibe el metabolismo de otros fármacos que se administran habitualmente de forma concomitante. En estudios específicos se ha demostrado que no hay…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

MajorAmisulpride
«Drugs Prolonging the QT Interval: BARHEMSYS causes dose- and concentration-dependent QT prolongation [see Clinical Pharmacology (12.2) ] . To avoid potential additive effects, avoid use of BARHEMSYS…»
FDA, section 7 · Open on DailyMed
ModerateHydroxyzine
«Sustratos de CYP2D6: codeína, dextrometorfano, flecainida, mexiletina, ondansetron, tamoxifeno, el tramadol.»
AEMPS, section 4.5 · Open on CIMA
Rifampicin
«antagonistas selectivos del receptor 5HT 3 (p. ej., ondansetrón)»
AEMPS, section 4.5 · Open on CIMA
Tramadol
«En un número limitado de estudios, la administración pre- o posquirúrgica del antiemético ondansetrón (antagonista 5-HT3) aumentó el requerimiento de tramadol en pacientes con dolor posquirúrgico.»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Ondansetron used for?

Ondansetron is evaluated for the following indications with varying evidence strength: Postoperative nausea and vomiting (evidence tier A), Chemotherapy-induced nausea and vomiting (evidence tier A), Stress and anxiety (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Ondansetron?

Common side effects of Ondansetron (≥ 1 in 100): Headache, Constipation, Warmth or flushing, Elevated liver enzymes. See the Safety section for uncommon and serious reactions.

Is Ondansetron safe during pregnancy?

Is Ondansetron compatible with breastfeeding?

Limited data. Milk concentrations are low; infant risk with single doses is minimal.

Who should not take Ondansetron?

Ondansetron is contraindicated in: Hypersensitivity to ondansetron or other 5-HT3 antagonists; Concurrent apomorphine; Congenital long-QT syndrome. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 02/06/2025
FDA / DailyMedLabel dated 07/29/2026

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