Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: 5-HT3 Receptor Antagonist
Main indication: Prevention and treatment of nausea and vomiting
Available forms3 forms · 8 strengths documentedShow all ↓
Oral · solid
Tablet 4 mgTablet 8 mgOrally disintegrating tablet 4 mg Zofran ODTOrally disintegrating tablet 8 mg Zofran ODTOral film 4 mg Setofilm / ZuplenzOral film 8 mg Setofilm / Zuplenz
Oral · liquid
Oral solution 4 mg/5 mL 0.8 mg/mL · 50 mL
Injection
2 mg/mL 2 mL and 4 mL ampoules · 2 mL syringes · 20 mL vials
Overview
Ondansetron (Zofran®) is a 5-HT3 receptor antagonist used in dogs and cats for the prevention and treatment of nausea and vomiting. It is available in both oral and injectable formulations and may be used alone or in combination with other antiemetic medications.
Ondansetron has demonstrated efficacy for chemotherapy-associated nausea and vomiting, for reducing vomiting in dogs with parvoviral enteritis, and for treating nausea in dogs with vestibular syndrome. Comparative studies suggest that its antiemetic effects are similar to or greater than those of metoclopramide, while maropitant may be equally or more effective in some situations.
Mechanism of Action (MOA): Ondansetron acts by blocking 5-HT3 (serotonin) receptors located both peripherally on vagal nerve terminals and centrally within the chemoreceptor trigger zone (CRTZ). Antagonism of these receptors mediates ondansetron’s antiemetic effects both centrally and peripherally. At typical therapeutic doses, ondansetron does not significantly affect gastrointestinal motility or transit time.
Indications
Ondansetron is used in dogs and cats for the prevention and treatment of nausea and vomiting associated with a variety of medical conditions and therapeutic interventions.
- Nausea and vomiting: Management of acute or ongoing nausea and vomiting in dogs and cats.
- Chemotherapy-associated nausea and vomiting: Prevention and treatment of nausea and emesis associated with chemotherapy administration.
- Parvoviral enteritis: Reduction of vomiting in affected dogs.
- Vestibular syndrome-associated nausea: Control of nausea in dogs with vestibular disease.
- Premedication-associated nausea and vomiting: Reduction of nausea and vomiting associated with certain sedative and analgesic premedication protocols.
- Signs not controlled by other antiemetics: Indicated for the management of nausea and vomiting in patients whose signs are not controlled by other drugs such as maropitant or metoclopramide.
- Obstructive sleep apnea: Used in the management of obstructive sleep apnea, where it has shown promise.
- Gastrointestinal disease: Used for vomiting associated with gastroenteritis, pancreatitis and inflammatory bowel disease.
Dosage (Reference)
Dog
Ondansetron is used extra-label in dogs for several antiemetic indications. Intravenous doses should be administered slowly.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Antiemetic | PO / Slow IV | 0.5–1 mg/kg | q8-12h; oral dosing q12-24h | Commonly used dosage, although supporting studies are limited. |
| Antiemetic (alternative dosage) | Slow IV | 0.1–0.2 mg/kg | q6-12h | Closer to human pediatric recommendations. If this dosage is initially ineffective it may be increased to 0.5 mg/kg. |
| Chemotherapy-induced nausea and vomiting | Slow IV | 0.3–0.5 mg/kg | q8-12h | Administer 30 minutes before chemotherapy. |
| Parvovirus-induced nausea and vomiting | Slow IV | 0.5 mg/kg | q8h | Ondansetron, metoclopramide and maropitant can be equally effective in reducing the frequency of vomiting in dogs with parvoviral enteritis. |
| Obstructive sleep apnea | PO | 1–2 mg/kg | Twice daily | Described as showing promise in this indication. |
| Vestibular syndrome-associated nausea | Slow IV | 0.5 mg/kg | Single dose | Reported for nausea in dogs with vestibular syndrome. |
| Antiemetic (constant-rate infusion) | Slow IV | 0.5 mg/kg loading dose, then 0.5 mg/kg/h | CRI | Continue the infusion for 6 hours after the loading dose. |
| Acute vomiting (more severe cases) | SC / Slow IV | 0.2–1 mg/kg | q8h | Antiemetics are not usually needed for mild acute vomiting, but may be needed in more severe cases. |
| Persistent vomiting unresponsive to treatment of the underlying disease | SC / Slow IV | 0.2–0.5 mg/kg | q8-12h | Reserve for patients whose vomiting persists despite treatment of the underlying disease. An oral alternative of 0.5–1.0 mg/kg every 12 hours is also described. |
| Chemotherapy-induced nausea and vomiting (alternative regimens) | Slow IV / SC / PO | 0.5–1 mg/kg | 30 minutes before chemotherapy | IV administration is consistently recommended; SC and PO administration have also been described at the same dose. |
| Vomiting during uremic crisis | Slow IV | 0.2–1 mg/kg | q12h | Given during uremic crisis to minimize vomiting and hyporexia due to nausea. |
Important dosing notes (dogs):
• Administer IV doses slowly.
• Oral absorption in dogs is low – less than 10% of the dose – and the half-life after oral dosing is short, which raises questions about the effectiveness of oral dosing in this species.
• Administer IV doses slowly.
• Oral absorption in dogs is low – less than 10% of the dose – and the half-life after oral dosing is short, which raises questions about the effectiveness of oral dosing in this species.
Cat
Ondansetron is used extra-label in cats for the management of vomiting and nausea. Intravenous administration should be performed slowly.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Acute vomiting | Slow IV / SC / IM / PO | 0.1–1 mg/kg: oral dosing 0.5–1 mg/kg | q6-12h; oral dosing q12-24h | Oral doses may need to be toward the high end of the range and given more frequently than IV or SC doses. |
| Chemotherapy-associated nausea and vomiting | Slow IV | 0.1–1 mg/kg | q6-12h | Administer 30 minutes before chemotherapy. |
| Vomiting associated with chronic kidney disease (IRIS Stage 1–2) | Slow IV / SC / PO | 0.1–0.2 mg/kg | q6-12h | This regimen uses progressively lower doses as the IRIS CKD stage advances; however, the effect of renal disease on ondansetron clearance in cats remains uncertain. An alternative unstaged regimen of 0.2–1 mg/kg IV every 12 hours has also been described. |
| Vomiting associated with chronic kidney disease (IRIS Stage 3) | Slow IV / SC / PO | 0.05–0.1 mg/kg | q6-12h | Dose is reduced as CKD stage advances. |
| Vomiting associated with chronic kidney disease (IRIS Stage 4) | Slow IV / SC / PO | 0.025–0.05 mg/kg | q6-12h | Lowest dose of the staged CKD schedule. |
| Reduction of vomiting associated with dexmedetomidine/buprenorphine premedication | IM | 0.22 mg/kg | With premedication | Administered in the same syringe; this reduced the incidence of nausea and vomiting to 33%, compared with 67% when given 30 minutes beforehand and 76% when not given at all. |
| Antiemetic (constant-rate infusion) | Slow IV | 0.5 mg/kg loading dose, then 0.5 mg/kg/h | CRI | Continue the infusion for 6 hours after the loading dose. |
| Acute vomiting (alternative regimen) | SC / Slow IV / PO | 0.5 mg/kg | q8h | A dose of 2 mg per cat every 8 hours is also common, which is half a tablet of the oral formulation. Reduce to twice daily in cats with liver disease. |
| Persistent vomiting unresponsive to treatment of the underlying disease | SC / Slow IV | 0.2–0.5 mg/kg | q8-12h | Reserve for patients whose vomiting persists despite treatment of the underlying disease. An oral alternative of 0.5–1.0 mg/kg every 12 hours is also described. |
| Chemotherapy-induced vomiting (alternative regimen) | Slow IV / PO | 0.5–1 mg/kg | 30 minutes before chemotherapy | Described as the best treatment for vomiting caused by chemotherapy. |
Important dosing notes (cats):
• Administer IV doses slowly.
• Oral dosing may require higher doses and more frequent administration than IV or SC dosing.
• Dose reductions are recommended as chronic kidney disease severity increases.
• Subcutaneous administration in cats is more bioavailable than oral dosing and results in a more prolonged exposure.
• Do not use a transdermal formulation in cats: it is not absorbed, and a gel applied to the ear pinna produced no measurable serum concentrations.
• Administer IV doses slowly.
• Oral dosing may require higher doses and more frequent administration than IV or SC dosing.
• Dose reductions are recommended as chronic kidney disease severity increases.
• Subcutaneous administration in cats is more bioavailable than oral dosing and results in a more prolonged exposure.
• Do not use a transdermal formulation in cats: it is not absorbed, and a gel applied to the ear pinna produced no measurable serum concentrations.
Warnings & Precautions
Ondansetron should be used cautiously in patients with certain underlying conditions or when administered with medications that may increase the risk of adverse cardiovascular or serotonergic effects.
- Hypersensitivity: Contraindicated in patients with known hypersensitivity to ondansetron or other 5-HT3 receptor antagonists.
- Ileus or gastric distention: Ondansetron may mask signs of ileus or gastric distention and should not be used in place of nasogastric suction or appropriate diagnostic assessment.
- Intestinal obstruction: Contraindicated. Antiemetics should not be given to a patient receiving outpatient care unless mechanical obstruction has been ruled out.
- Hepatic dysfunction: Use with caution in patients with liver disease, as drug absorption may be increased and elimination half-life may be prolonged. Dosage adjustment may be warranted in severe hepatic impairment; in cats with liver disease the dosing interval should be extended, as exposure is increased and clearance is reduced.
- MDR1 mutation (dogs): Use cautiously in dogs with the MDR1 gene mutation, as the role of canine P-glycoprotein in ondansetron transport has not been fully established.
- QT interval prolongation: Dose-related QT prolongation has been reported, and cases of torsades de pointes have occurred in people. Patients with electrolyte abnormalities, underlying cardiac disease, or those receiving other QT-prolonging medications may be at increased risk.
- Serotonin syndrome: Use cautiously with medications that increase serotonin activity, as serotonin syndrome has been reported in humans receiving ondansetron.
- Pregnancy: Safety during pregnancy has not been clearly established. High-dose rodent studies did not show overt fetal toxicity or teratogenicity, but a review of use in pregnant women found a small increase in cardiac abnormalities and concluded it should be avoided in the first trimester if possible.
- Nursing animals: Use with caution in lactating patients; ondansetron is excreted in maternal milk in rats.
Drug Interactions
Several clinically important interactions have been reported or are theoretically possible with ondansetron. Additional monitoring may be warranted when used concurrently with the following medications.
- Apomorphine: May reduce the emetic effect of apomorphine. Severe hypotension and loss of consciousness have been reported in humans receiving both drugs, and their combined use is contraindicated in people.
- Azole antifungals (e.g., itraconazole, posaconazole): May inhibit ondansetron metabolism and increase the risk of QT interval prolongation.
- Cisplatin: Plasma cisplatin concentrations may be decreased.
- Cyclophosphamide: Plasma cyclophosphamide concentrations may be decreased.
- QT-prolonging drugs (e.g., amiodarone, cisapride, procainamide, quinidine, sotalol): May have additive effects on the QT interval, increasing the risk of serious arrhythmias.
- Monoamine oxidase inhibitors (MAOIs; e.g., amitraz, methylene blue, selegiline): May increase the risk of serotonin syndrome; this increased risk has been reported in humans.
- Metformin: Ondansetron may increase serum metformin concentrations.
- P-glycoprotein inhibitors (e.g., amiodarone, cyclosporine, diltiazem, quinidine): In humans these drugs may increase serum concentrations of ondansetron; whether ondansetron is a P-glycoprotein substrate in veterinary patients is unclear.
- Ropinirole: Ondansetron may reduce the emetic effect of ropinirole.
- Serotonergic drugs (e.g., clomipramine, fluoxetine, mirtazapine, trazodone): May increase the risk of serotonin syndrome; this increased risk has been reported in humans.
- Tramadol: Concurrent use may reduce the efficacy of both drugs in humans and the veterinary significance is uncertain, although one reference advises that ondansetron may reduce tramadol effectiveness and that the tramadol dose may need to be increased.
- Intravenous incompatibility: A precipitate may form when ondansetron is mixed with alkaline solutions, and it is reportedly incompatible with amphotericin B (conventional and lipid-based forms), ampicillin/sulbactam, furosemide, pantoprazole and phenobarbital sodium.
- Metoclopramide: Compatibility with metoclopramide depends on the concentrations, diluent, pH, temperature and administration method. Because precipitation may occur, do not mix or administer through the same IV line unless compatibility under the exact conditions has been confirmed; otherwise, administer separately and flush the line between drugs.
- Strength of the evidence: These interactions have either been reported or are theoretical in humans or animals, and other drug interactions have not been reported in animals.
Side Effects & Overdose
Side Effects
Ondansetron appears to be well tolerated in dogs and cats. Its adverse effects have not been reported in animals; the effects listed below are drawn from human experience.
- Gastrointestinal effects: Constipation and diarrhea may occur; reported in humans at an incidence of less than 10%.
- Sedation: Reported in humans at an incidence of less than 10%.
- Extrapyramidal signs: Neurologic signs such as head shaking may occur, at an incidence in humans of less than 10%.
- Increased liver enzymes: Occasional elevations in hepatic enzyme activities have been reported in humans, at an incidence of less than 10%.
- Cardiovascular effects: Arrhythmias and hypotension may occur, reported in humans at an incidence of less than 10%.
- Vision changes: Transient visual disturbances, including blindness during IV administration, have been reported rarely in humans.
- Headache and hypersensitivity: Headaches occur in 10% to 25% of humans, though the relevance for veterinary patients is unknown, and rarely, hypersensitivity reactions have been reported.
- Concurrent cancer drugs: During chemotherapy, severe adverse effects can occur from the concurrent cancer drugs and may be difficult to distinguish from ondansetron effects.
Overdose
Available overdose evidence is limited to humans. In humans, overdoses of up to 10 times the labeled dosage did not result in significant morbidity.
- Clinical effects: Overdoses of up to ten times the labeled dosage did not cause significant morbidity in humans.
- Management: Treatment should be supportive.
- Monitoring: For a known or suspected overdose, consult a 24-hour poison control center that provides veterinary-specific information.
Key Notes
Practical clinical points that may help optimize the use of ondansetron in dogs and cats:
- Combination therapy: Ondansetron may be used in combination with other antiemetic medications when additional control of nausea and vomiting is required.
- Comparable efficacy: Ondansetron, metoclopramide, and maropitant have all demonstrated effectiveness in reducing vomiting frequency in dogs with parvoviral enteritis.
- Effect on GI motility: At typical therapeutic dosages, ondansetron does not significantly affect gastrointestinal motility or transit time.
- IV administration: Intravenous doses should be administered slowly; in human medicine, administration over at least 30 seconds and preferably over 2–5 minutes is recommended.
- Tolerability: Ondansetron is generally considered a well-tolerated antiemetic in veterinary patients.
- Pharmacokinetics: In cats oral bioavailability is about 32% and subcutaneous about 75%, with elimination half-lives of roughly 2 hours after IV, 1.2 hours after oral and 3.2 hours after subcutaneous dosing. In healthy dogs oral bioavailability was measured at about 5%, raising concern about oral efficacy. Reported canine oral half-life varies by source – 30 minutes in one reference, and 1.3 hours after a single 8 mg dose in healthy beagles in another. Most of ondansetron is metabolized by the liver (95%).
- Not for motion sickness: Drugs of this class are not effective against emesis caused by motion sickness.
- Salt versus base: Product strengths are expressed as ondansetron base; 1 mg of ondansetron is equivalent to 1.25 mg of ondansetron hydrochloride dihydrate.
- Storage and handling: Store oral products in tight, light-resistant containers at 20–25°C (excursions of 15–30°C are permitted for the oral solution), and the injection at 2–25°C protected from light. Keep orally disintegrating tablets in their original foil blisters, handle them with dry hands, give them immediately on opening, and discard opened or unused tablets and remnants. Solutions diluted for IV infusion retain potency for 48 hours at room temperature, but the manufacturer recommends discarding them 24 hours after dilution.
- Dosing interval matters: 0.5 mg/kg every 12 hours by mouth or intravenously may be unlikely to maintain effective concentrations, and the longer subcutaneous half-life may make subcutaneous administration better suited.
- Compounding: An ondansetron 0.8 mg/mL oral suspension can be prepared by crushing tablets and suspending them in Ora-Plus diluted with an equal amount of Ora-Sweet, Syrpalta or cherry syrup, which is stable for 6 weeks refrigerated; using SyrSpend SF pH 4 gives a 90-day beyond-use date refrigerated or at room temperature.
- Administration with food: The oral medication may be given with or without food.
- Strength of the evidence: Use in dogs and cats is based primarily on anecdotal evidence and recommendations from clinical experts, and well-controlled clinical studies in animals are lacking.
- Monitoring: Assess clinical efficacy and monitor gastrointestinal signs in a vomiting patient.
- When an antiemetic is not working: If a patient receiving outpatient care continues to vomit despite an antiemetic, hospitalize for further diagnostics and inpatient medical care. Further diagnostics are also warranted if vomiting is not improving or is getting more severe, and if it persists beyond 7 days or recurs despite appropriate therapy, consider chronic vomiting etiologies.
