Ondansetron is an anti-nausea drug that blocks the 5-HT3 type of serotonin receptor. It was first approved in the US in 1991 as Zofran injection, and tablets, orally disintegrating tablets (ODT) and an oral solution followed. It is one of the most widely used antiemetics (anti-vomiting drugs) in hospitals and cancer care.
The FDA label approves ondansetron only to prevent nausea and vomiting from cancer chemotherapy, from certain kinds of radiotherapy, and after surgery. It is also prescribed off-label for other kinds of nausea, including nausea from GLP-1 medicines such as semaglutide and tirzepatide. No trial has tested ondansetron alone in that setting. The main labeled risks are QT prolongation (a change in the heart’s electrical rhythm), serotonin syndrome, and constipation.
This page summarizes what the FDA labels, the FDA safety record and the published guidance report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Selective 5-HT3 receptor antagonist (antiemetic) |
| Brands | Zofran (tablets, ODT, oral solution, injection), now held by Sandoz; Zuplenz (oral film). All brand products are listed as discontinued in Drugs@FDA; generics are available |
| First US approval | January 4, 1991 (Zofran injection, NDA 020007) |
| Routes | Oral tablet, ODT, oral solution, intravenous (IV), intramuscular (IM) |
| Oral strengths (label) | 4 mg and 8 mg tablets and ODT; 4 mg/5 mL solution |
| Half-life (label) | About 3–6 h in healthy adults after an 8 mg tablet; about 20 h in severe liver impairment |
| Approved uses | Prevention of nausea and vomiting from chemotherapy, radiotherapy and surgery |
| Boxed warning | None |
| Key warnings | QT prolongation and torsade de pointes, serotonin syndrome, masking of ileus |
| US status | Prescription drug; the label lists no controlled-substance schedule |
What it is
Ondansetron’s chemical name is (±)-1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one. The base has the formula C₁₈H₁₉N₃O and a molecular weight of 293.4 g/mol. Tablets and the oral solution contain it as the hydrochloride dihydrate, while the ODT contains the base (Zofran oral label; PubChem).
The label explains the mechanism as follows. Chemotherapy appears to release serotonin from cells in the lining of the small intestine. That serotonin can stimulate 5-HT3 receptors on vagus nerve endings and in the brain’s vomiting center (the chemoreceptor trigger zone), which starts the vomiting reflex. Ondansetron blocks these receptors. The label notes it is not certain whether the drug acts mainly in the gut, the brain, or both.
Ondansetron differs from older antiemetics in what it does not do:
- It is not a dopamine blocker, unlike metoclopramide or prochlorperazine. It has no effect on prolactin.
- It does not speed up the stomach. Single IV doses had no effect on gastric emptying or small-bowel transit in healthy people.
- With repeated doses, it slows transit through the colon, which explains why constipation is a common side effect.
Pharmacokinetics
From the Zofran oral and injection labels (Zofran oral label; Zofran injection label):
| Parameter | Label value |
|---|---|
| Oral bioavailability | About 56% after an 8 mg tablet (some first-pass loss in the liver); slightly higher with food |
| Time to peak (8 mg tablet) | About 1.7–2.2 h |
| Protein binding | 70–76% |
| Metabolism | Extensive, in the liver, by CYP3A4 (main), CYP2D6 and CYP1A2; about 5% leaves unchanged in urine |
| Half-life, healthy adults 18–40 (8 mg tablet) | 3.1 h in men, 3.5 h in women |
| Half-life, adults over 75 | 4.5 h in men, 6.2 h in women |
| Half-life, adult cancer patients (IV) | About 4.0 h |
| Half-life, mild-to-moderate liver impairment | 11.6 h (vs 5.7 h in the comparison group) |
| Half-life, severe liver impairment (Child-Pugh 10 or more) | About 20 h |
Women had higher blood levels than men after the same tablet dose, partly due to lower body weight. Because several enzymes break ondansetron down, the label states that loss of one (for example, a genetic CYP2D6 deficiency) is likely to be compensated by the others. Strong CYP3A4 inducers (phenytoin, carbamazepine, rifampin) lowered ondansetron levels, but the label does not recommend a dose change.
Approved medical use
Oral forms (tablets, ODT, oral solution)
The oral label approves ondansetron to prevent nausea and vomiting from:
- highly emetogenic chemotherapy, including cisplatin at 50 mg/m² or more;
- initial and repeat courses of moderately emetogenic chemotherapy;
- radiotherapy given as total body irradiation, a single high-dose fraction to the abdomen, or daily fractions to the abdomen;
- surgery (postoperative nausea and vomiting).
| Setting (adults) | Labeled oral dosage |
|---|---|
| Highly emetogenic chemotherapy | Single 24 mg dose 30 minutes before chemotherapy |
| Moderately emetogenic chemotherapy | 8 mg 30 minutes before, 8 mg 8 hours later, then 8 mg every 12 hours for 1–2 days after chemotherapy |
| Total body irradiation | 8 mg 1–2 hours before each fraction |
| Abdominal radiotherapy | 8 mg 1–2 hours before, then 8 mg every 8 hours (schedule depends on single vs daily fractions) |
| Postoperative | 16 mg 1 hour before anesthesia |
In children 4–11 years, the moderately emetogenic chemotherapy dose is 4 mg, and in ages 12–17 it is the adult 8 mg regimen. In severe liver impairment the total daily dose should not exceed 8 mg. No adjustment is labeled for kidney impairment or for older adults (Zofran oral label).
Injection
The injection is approved to prevent chemotherapy-induced nausea and vomiting in patients 6 months and older, and postoperative nausea and vomiting in patients 1 month and older (Zofran injection label):
| Setting | Labeled IV/IM dose |
|---|---|
| Chemotherapy | 0.15 mg/kg per dose (maximum 16 mg per dose), infused over 15 minutes, 30 minutes before chemotherapy and again 4 and 8 hours later |
| Postoperative, adults and children over 40 kg | Single 4 mg dose IV (over at least 30 seconds) or IM |
| Postoperative, children 40 kg or less | Single 0.1 mg/kg IV dose |
The 16 mg cap per IV dose dates from 2012. That year FDA reported that a single 32 mg IV dose could prolong the QT interval, and the manufacturer removed that dose from the label. FDA said the change did not affect oral dosing (FDA Drug Safety Communication, 2012).
Brand and generic status
Drugs@FDA lists every Zofran brand product (tablets, ODT, oral solution and injection) and the Zuplenz oral film as discontinued. The Zofran labels were last updated in 2025 under Sandoz, and ondansetron remains widely available as generics (Drugs@FDA, NDA 020103; Drugs@FDA, NDA 020007).
What the research shows
Chemotherapy and radiotherapy (label trials)
The trials behind the label used complete control of vomiting as the main outcome (Zofran oral label):
| Trial | n | Ondansetron result | Comparator |
|---|---|---|---|
| Cisplatin 50 mg/m² or more, single 24 mg oral dose | 357 (3 dose arms) | 66% had no vomiting and no rescue drug over 24 h | Historical placebo: over 90% vomit without an antiemetic |
| Moderately emetogenic (cyclophosphamide + doxorubicin), 8 mg regimen, 3 days | 67 | 61% had zero vomiting episodes | Placebo 6% (p under 0.001) |
| Twice vs three times daily 8 mg, moderately emetogenic | 336 | 61% vs 58% with zero episodes | Twice daily as effective as three times |
| Single high-dose abdominal radiotherapy | 105 | Better complete control of vomiting | Metoclopramide 10 mg |
| Daily fractionated abdominal radiotherapy | 135 | Better complete control of vomiting | Prochlorperazine 10 mg |
In the cisplatin trial, the 24 mg single dose also prevented nausea in 56% of patients, versus 36% on 8 mg twice daily (p = 0.001). A 32 mg single oral dose did no better than 24 mg, and the label does not recommend it.
Postoperative nausea and vomiting
Both the oral (16 mg before anesthesia) and injectable (4 mg IV or IM) forms are approved for this use. The injection label notes that routine prevention is not recommended when little postoperative nausea is expected (Zofran injection label).
Nausea from GLP-1 medicines
Nausea is the most common side effect of GLP-1 receptor agonists. On the labels, nausea affected 44% of adults on Wegovy 2.4 mg vs 16% on placebo, and 25–29% on Zepbound vs 8% on placebo (Wegovy label; Zepbound label). Ondansetron is not FDA-approved for this use, and the evidence for it is indirect:
- No trials of ondansetron alone with semaglutide or tirzepatide. A PubMed search found no randomized trial testing ondansetron for nausea from either drug.
- One study used it with an older GLP-1 drug. In a phase 1 study of 120 healthy adults given a single 10 µg dose of exenatide, 60 received oral metoclopramide 10 mg plus ondansetron 8 mg 30 minutes beforehand (Ellero et al., Diabet Med 2010). Nausea occurred in 16.7% of premedicated subjects vs 61.7% of the others, and vomiting in 6.7% vs 38.3% (p under 0.0001 for both). Exenatide blood levels did not change. However, the premedication was given at the investigator’s discretion rather than by randomization, the analysis was retrospective, both drugs were always given together, and only one dose was studied. The authors note it is unknown whether either drug alone would work. Somnolence was more common with premedication (8.3% vs 1.7%).
- A Spanish expert consensus recommends diet and eating-habit changes first, then an antiemetic and/or prokinetic drug if nausea persists. It names domperidone, metoclopramide and cinitapride but does not mention ondansetron. If antiemetics are still needed after more than a month at the maintenance dose, it suggests considering a lower GLP-1 dose (Gorgojo-Martínez et al., J Clin Med 2022).
- A US joint advisory from four lifestyle-medicine, nutrition and obesity societies says anti-nausea drugs can help during the start of treatment and dose increases. It adds that agents such as prochlorperazine “may be preferable” to serotonin-targeting drugs like ondansetron, because ondansetron can worsen constipation (Mozaffarian et al., Am J Clin Nutr 2025).
Constipation overlaps with GLP-1 side effects. It affected 24% of adults on Wegovy 2.4 mg (vs 11% on placebo) and 11–17% on Zepbound (vs 5%). Both labels also list postmarketing reports of ileus (stalled bowel), intestinal obstruction and severe constipation with fecal impaction (Wegovy label; Zepbound label). The ondansetron label separately warns that it can mask a developing ileus (see below). No study we found has measured how often these effects occur when the drugs are combined.
Side effects and risks
Common side effects
In label trials with moderately emetogenic chemotherapy (ondansetron 8 mg twice daily, n = 242, vs placebo, n = 262) (Zofran oral label):
| Adverse reaction | Ondansetron | Placebo |
|---|---|---|
| Headache | 24% | 13% |
| Malaise/fatigue | 13% | 2% |
| Constipation | 9% | under 1% |
| Diarrhea | 6% | 4% |
After a single 16 mg dose before surgery (n = 550 vs 531 on placebo), headache occurred in 9% vs 5% and hypoxia (low blood oxygen) in 9% vs 7%. Transient rises in liver enzymes above twice the upper limit occurred in about 1–2% of 723 patients on chemotherapy.
QT prolongation
The label warns that ondansetron prolongs the QT interval, and postmarketing cases of torsade de pointes (a dangerous ventricular arrhythmia) have been reported. In a crossover trial in 58 healthy adults, the maximum mean QTcF increase over placebo was (Zofran oral label):
| IV dose (over 15 minutes) | Mean QTcF increase vs placebo |
|---|---|
| 8 mg (measured) | 5.6 ms |
| 16 mg (model-predicted) | 9.1 ms |
| 24 mg (model-predicted) | 14.0 ms |
| 32 mg (measured) | 19.5 ms |
The effect rose with blood concentration, and 8 mg did not prolong the QT interval to a clinically relevant extent. The label says to avoid ondansetron in congenital long QT syndrome, and recommends ECG monitoring in people with low potassium or magnesium, heart failure, slow heart rhythms, or who take other QT-prolonging drugs. FDA first announced a safety review of ondansetron and abnormal heart rhythms in September 2011 (FDA Drug Safety Communication, 2012).
Serotonin syndrome
Serotonin syndrome has been reported with 5-HT3 antagonists alone, but most cases involved other serotonergic drugs, and some were fatal. The label names (Zofran oral label):
- SSRIs and SNRIs (common antidepressants);
- monoamine oxidase inhibitors, mirtazapine and lithium;
- fentanyl and tramadol;
- intravenous methylene blue.
Symptoms can include agitation or confusion, fast heart rate, sweating, fever, tremor, muscle rigidity or jerks, and seizures. Most reported cases occurred in post-anesthesia units or infusion centers. Cases have also followed overdose of ondansetron alone, including accidental ingestion by young children.
Constipation and masked ileus
Ondansetron caused constipation in 9% of chemotherapy patients vs under 1% on placebo, and the label states that repeated dosing slows colonic transit. After abdominal surgery or during chemotherapy-induced nausea, ondansetron may mask a progressive ileus or gastric distension. The label says to watch for decreased bowel activity in people at risk of bowel obstruction. Ondansetron does not stimulate gut movement and should not replace nasogastric suction.
Other warnings
- Hypersensitivity: anaphylaxis and bronchospasm have been reported, including in people allergic to other 5-HT3 antagonists.
- Myocardial ischemia: reported mostly with IV use, sometimes immediately after the dose. Coronary artery spasm appears to be the most common cause.
- Phenylketonuria: the ODT contains aspartame (under 0.03 mg phenylalanine per tablet).
- Postmarketing reports: arrhythmias, transient blindness (mostly with IV use, resolving within minutes to 48 h), oculogyric crisis and other dystonic reactions, and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
Pregnancy
Ondansetron is not approved for nausea in pregnancy. The label states that published studies of birth defects are inconsistent and have important limitations. Some found small increases in cardiac or oral cleft defects (for example, RR 1.24 for oral clefts with first-trimester oral use in one Medicaid cohort), while others did not.
Interactions
From the label (Zofran oral label):
| Drug or class | Effect |
|---|---|
| Apomorphine | Contraindicated: profound low blood pressure and loss of consciousness |
| Serotonergic drugs (SSRIs, SNRIs, MAOIs, tramadol, fentanyl, lithium, mirtazapine) | Risk of serotonin syndrome |
| Other QT-prolonging drugs | Additive QT risk; ECG monitoring recommended |
| Strong CYP3A4 inducers (phenytoin, carbamazepine, rifampin) | Lower ondansetron levels; no labeled dose change |
| Tramadol | Two small trials suggested patients needed more tramadol for pain control |
| Carmustine, etoposide, cisplatin; high-dose methotrexate | No effect on ondansetron levels; ondansetron did not raise methotrexate levels |
Ondansetron itself does not appear to induce or inhibit liver CYP enzymes.
Who should not use it
The label contraindicates ondansetron in people with known hypersensitivity to it and in people taking apomorphine. It also says to avoid it in congenital long QT syndrome. The total daily dose is capped at 8 mg in severe liver impairment.
Key takeaways
- Approved only for prevention in three settings. The FDA label covers chemotherapy, certain radiotherapy, and postoperative nausea and vomiting. All other uses are off-label.
- Short half-life, longer in liver disease. The half-life is about 3–6 hours in healthy adults and about 20 hours in severe liver impairment, where the daily dose is capped at 8 mg.
- QT risk rises with dose. A single 32 mg IV dose raised QTcF by about 20 ms and was removed from the label in 2012. Single IV doses are now capped at 16 mg, and the drug should be avoided in congenital long QT syndrome.
- Serotonin syndrome is a labeled warning. Most cases involved other serotonergic drugs such as SSRIs, SNRIs, tramadol or fentanyl.
- Constipation is common. It affected 9% vs under 1% on placebo, and ondansetron can mask a developing ileus. Both points matter when it is combined with GLP-1 drugs, which also cause constipation.
- GLP-1 nausea evidence is indirect. No trial has tested ondansetron alone with semaglutide or tirzepatide. One non-randomized single-dose exenatide study combined it with metoclopramide. A US advisory suggests prochlorperazine may be preferable because of constipation.
Sources
- Sandoz Inc. Zofran (ondansetron hydrochloride) tablets, Zofran ODT (ondansetron) orally disintegrating tablets, Zofran (ondansetron hydrochloride) oral solution, prescribing information, NDA 020103/S-039, 020605/S-023, 020781/S-023, revised 02/2025. FDA.
- Sandoz Inc. Zofran (ondansetron) injection, prescribing information, NDA 020007/S-050, 2025. FDA.
- Food and Drug Administration. Drugs@FDA: Zofran, NDA 020103 and NDA 020007 (approval history and marketing status). Drugs@FDA, NDA 020103; Drugs@FDA, NDA 020007.
- Food and Drug Administration. FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran). June 29, 2012. FDA (archived).
- National Center for Biotechnology Information. PubChem Compound Summary: Ondansetron, CID 4595. PubChem.
- Novo Nordisk. Wegovy (semaglutide) injection and tablets, prescribing information. DailyMed.
- Eli Lilly and Company. Zepbound (tirzepatide) injection, prescribing information. DailyMed.
- Ellero C, Han J, Bhavsar S, et al. Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjects. Diabet Med. 2010;27(10):1168–1173. PubMed.
- Gorgojo-Martínez JJ, Mezquita-Raya P, Carretero-Gómez J, et al. Clinical recommendations to manage gastrointestinal adverse events in patients treated with Glp-1 receptor agonists: a multidisciplinary expert consensus. J Clin Med. 2022;12(1):145. PubMed.
- Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Am J Clin Nutr. 2025;122(1):344–367. PubMed.