Brand name: Zofran
Drug class: 5-HT3 Receptor Antagonists
VA class: GA700
Chemical name: 1,2,3,9-Tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H-carbazol-4-one monohydrochloride dihydrate
Molecular formula: C₁₈H₁₉N₃O•ClH• 2H₂O
CAS number: 103639-04-9

Medically reviewed by Drugs.com on Jan 10, 2024. Written by ASHP.

Introduction

Antiemetic; selective, first-generation inhibitor of type 3 serotonergic (5-HT₃) receptors.

Uses for Ondansetron

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with emetogenic cancer chemotherapy; may use orally with highly emetogenic chemotherapy (i.e., cisplatin ≥50 mg/m²) or initial and repeat courses of moderately emetogenic chemotherapy, or IV with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin.

For prevention of nausea and vomiting associated with highly emetogenic chemotherapy regimens (including an anthracycline plus cyclophosphamide), ASCO recommends a 3-drug antiemetic regimen consisting of an NK₁ receptor antagonist (e.g., either oral aprepitant or IV fosaprepitant), a 5-HT₃ receptor antagonist (e.g., dolasetron, granisetron, ondansetron, palonosetron), and dexamethasone. ASCO states that fixed-combination netupitant and palonosetron plus dexamethasone is an additional treatment option.

For moderately emetogenic chemotherapy regimens, ASCO recommends a 2-drug antiemetic regimen preferably consisting of palonosetron and dexamethasone. If palonosetron is not available, a first-generation 5-HT₃ receptor antagonist (preferably granisetron or ondansetron) may be substituted. Limited evidence suggests that aprepitant may be added to this regimen; in such cases, use of any 5-HT₃ receptor antagonist is appropriate.

For chemotherapy regimens with a low emetogenic risk, ASCO recommends administration of a single dose of dexamethasone prior to chemotherapy.

For chemotherapy regimens with minimal emetogenic risk, ASCO states that routine antiemetic administration is not necessary.

Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting.

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.

Recommended for patients who, in the clinician’s judgement, must avoid nausea and/or vomiting postoperatively, even when anticipated incidence is low.

Radiation-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with radiation, either total body irradiation or single high-dose fraction or daily fractionated radiation to the abdomen.

Ondansetron Dosage and Administration

Administration

Administer orally, by IV infusion, or by IV or IM injection.

Oral Administration

Administer orally as conventional tablet, orally disintegrating tablet, or oral solution.

Commercially available oral solution and orally disintegrating tablets may be used interchangeably.

Do not remove orally disintegrating tablet from blister until just prior to dosing; do not push through foil. With dry hands, peel open blister package, and gently remove the tablet; place tablet on tongue to dissolve, and swallow with saliva.

Administration of orally disintegrating tablet with liquid is not necessary.

IV Administration

For prevention of cancer chemotherapy-induced nausea/vomiting, administer by IV infusion using diluted injection.

For prevention of postoperative nausea and vomiting, administer undiluted by IV injection.

Dilution

For IV infusion, dilute ondansetron hydrochloride injection in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection.

For IV injection, no dilution required.

Rate of Administration

IV infusion: Infuse over 15 minutes.

IV injection: Inject over a period of ≥30 seconds, preferably over 2–5 minutes.

IM Administration

For prevention of postoperative nausea and vomiting in adults, may administer undiluted by IM injection as an alternative to IV injection. (See Postoperative Nausea and Vomiting under Dosage and Administration.)

Dosage

Available as ondansetron hydrochloride dihydrate (for oral or IV use) and as ondansetron base (orally disintegrating tablets); dosage expressed in terms of ondansetron.

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

Oral

Children 4–11 years of age: Initially, 4 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by subsequent 4-mg doses given 4 and 8 hours after first dose. Continue with 4 mg every 8 hours for 1–2 days after completion of chemotherapy.

Children ≥12 years of age: Initially, 8 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by a subsequent 8-mg dose given 8 hours after first dose. Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.

IV

Pediatric patients 6 months to 18 years of age: 0.15 mg/kg (maximum 16 mg per dose) by IV infusion beginning 30 minutes before start of emetogenic chemotherapy, followed by subsequent 0.15-mg/kg doses given 4 and 8 hours after first dose.

Postoperative Nausea and Vomiting

Prevention

IV

Infants and children 1 month to 12 years of age weighing ≤40 kg: 0.1 mg/kg as a single dose by IV injection immediately before or after induction of anesthesia.

Children ≤12 years of age weighing >40 kg: 4 mg as a single dose by IV injection immediately before or after induction of anesthesia.

Treatment

IV

Infants and children 1 month to 12 years of age weighing ≤40 kg: 0.1 mg/kg as a single dose by IV injection postoperatively, if nausea and/or vomiting occur shortly after surgery.

Children ≤12 years of age weighing >40 kg: 4 mg as a single dose by IV injection postoperatively, if nausea and/or vomiting occur shortly after surgery.

Efficacy of a second dose administered postoperatively after a single, prophylactic, preinduction IV dose has failed to achieve adequate control of postoperative nausea and vomiting has not been evaluated in children; such repeat doses are not effective in adults.

Adults

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

Oral

Initially, 8 mg given 30 minutes before administration of moderately emetogenic chemotherapy, followed by a subsequent 8-mg dose given 8 hours after first dose. Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.

24 mg as a single dose given 30 minutes before administration of single-day highly emetogenic chemotherapy.

IV

0.15 mg/kg (maximum 16 mg per dose) by IV infusion beginning 30 minutes before administration of emetogenic chemotherapy, followed by 0.15 mg/kg infused 4 and 8 hours after first dose.

Single IV dose of 32 mg no longer recommended (see Cardiac Effects under Cautions); efficacy and safety of alternative single-dose IV regimens for prevention of cancer chemotherapy-induced nausea and vomiting not established.

Postoperative Nausea and Vomiting

Prevention

Oral

16 mg as a single dose given 1 hour before induction of anesthesia.

IV

4 mg as a single dose by IV injection (undiluted) immediately before induction of anesthesia.

Limited information available regarding dosage in patients weighing >80 kg.

If adequate control of postoperative nausea and vomiting is not achieved after a single, prophylactic, preinduction IV dose, a second IV dose postoperatively does not provide additional control of nausea and vomiting.

If nausea and/or vomiting occur shortly (within 2 hours) after surgery in a patient who did not receive prophylactic antiemetic therapy, 4 mg as a single dose by IV injection (undiluted) postoperatively.

IM

4 mg as a single dose by IM injection (undiluted) as an alternative to IV administration.

Limited information available regarding dosage in patients weighing >80 kg.

Radiation-induced Nausea and Vomiting

Prevention, Usual Dosage

Oral

Usually, 8 mg 3 times daily.

Prevention, for Total Body Irradiation

Oral

8 mg 1–2 hours before each fraction of radiotherapy administered each day.

Prevention, for Single High-dose Fraction Radiation to Abdomen

Oral

8 mg 1–2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1–2 days after completion of radiotherapy.

Prevention, for Daily Fractionated Radiation to Abdomen

Oral

8 mg 1–2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Prescribing Limits

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

0.15 mg/kg (maximum 16 mg per dose). (See Cardiac Effects under Cautions.)

Adults

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

0.15 mg/kg (maximum 16 mg per dose). (See Cardiac Effects under Cautions.)

Special Populations

Hepatic Impairment

Do not exceed total daily dosage of 8 mg (parenteral or oral) in patients with severe hepatic impairment (Child-Pugh score ≥10); no experience to date with continuation beyond the first day of IV therapy.

Renal Impairment

No dosage adjustment required, but no experience to date with continuation beyond the first day of therapy.

Geriatric Patients

No dosage adjustment required.

Cautions for Ondansetron

Contraindications

• Known hypersensitivity to ondansetron or any ingredient in the formulation.

• Concomitant use with apomorphine. (See Specific Drugs under Interactions.)

Warnings/Precautions

Sensitivity Reactions

Sensitivity reactions, including anaphylactic reaction, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, and stridor, reported rarely.

Possible hypersensitivity reactions in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.

Cardiac Effects

Dose-related prolongation of QT interval and cases of torsades de pointes reported. ECG alterations including QT-interval prolongation reported mainly with IV administration.

In healthy adults, IV ondansetron doses of 8 or 32 mg produced maximum mean baseline-corrected increases in QT_c interval (QT interval corrected for heart rate using Fridericia’s formula) relative to placebo of 5.8 or 19.6 milliseconds, respectively. Individual IV doses should not exceed 16 mg. (See Dosage under Dosage and Administration.)

Avoid use of ondansetron in patients with congenital long QT syndrome.

Monitor ECG in patients with electrolyte abnormalities (e.g. hypokalemia, hypomagnesemia), CHF, or bradyarrhythmias and in those receiving other drugs known to prolong the QT interval. Correct electrolyte abnormalities prior to IV administration of ondansetron.

GI Precautions

Does not stimulate gastric or intestinal peristalsis; do not use as a substitute for nasogastric suction.

May mask progressive ileus and/or gastric distention in patients undergoing abdominal surgery or in those with chemotherapy-induced nausea and vomiting.

Phenylketonuria

Each 4- or 8-mg Zofran ODT orally disintegrating tablet contains aspartame (Nutrasweet), which is metabolized in the GI tract to provide <0.03 mg of phenylalanine per tablet.

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk in rats; not known whether distributed into human milk. Caution advised if used in nursing women.

Pediatric Use

Safety and efficacy of oral or IV ondansetron for prevention of chemotherapy-induced emesis generally comparable to that in adults.

Little information available on IV use for prevention of postoperative nausea and vomiting in pediatric patients <1 month of age or for prevention of chemotherapy-induced nausea and vomiting in pediatric patients <6 months of age. Little information available on oral dosage in children ≤4 years of age.

Because clearance is reduced in infants 1–4 months of age compared with those >4 to 24 months of age, closely monitor infants <4 months of age. (See Half-life under Pharmacokinetics.)

Efficacy of single 24-mg oral dose for prevention of nausea and vomiting induced by highly emetogenic chemotherapy or oral therapy for prevention of radiation-induced or postoperative nausea and vomiting not established in children <18 years of age.

Geriatric Use

No substantial differences in safety or efficacy in patients >65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Clearance is decreased and half-life increased in patients with hepatic impairment. Use with caution and at reduced dosage in patients with severe hepatic impairment. (See Special Populations under Dosage and Administration.)

Common Adverse Effects

Headache, diarrhea, dizziness, constipation, fever, drowsiness/sedation, shivers, malaise/fatigue, hypoxia, pyrexia, urinary retention, pruritus.

Drug Interactions

Substrate of CYP1A2, CYP2D6, and CYP3A4 in vitro; does not appear to induce or inhibit CYP isoenzymes.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP1A2, CYP2D6, or CYP3A4; potential pharmacokinetic interaction (altered ondansetron metabolism). Based on available data, no dosage adjustment recommended for patients on these drugs.

Drugs that Prolong QT Interval

Potential additive effect on QT-interval prolongation. Monitor ECG during concomitant use. (See Cardiac Effects under Cautions.)

Specific Drugs

Ondansetron Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract after oral administration. Mean bioavailability after administration of single 8-mg tablet is approximately 56%; increased bioavailability expected with dosages >8 mg.

Peak plasma concentrations are attained approximately 1.5–2.2 hours after oral administration, approximately 25 minutes after IV infusion, or 41 minutes after IM injection.

Commercially available oral solution and orally disintegrating tablets (4- or 8-mg doses) are bioequivalent to corresponding doses of conventional tablets.

Food

Food slightly increases bioavailability.

Special Populations

Extent and rate of absorption are increased in women compared with men; not known whether differences are clinically important.

Distribution

Extent

Circulating drug distributes into erythrocytes.

Distributed into milk in rats; not known whether distributed into human milk.

Plasma Protein Binding

70–76%.

Elimination

Metabolism

Extensively metabolized in the liver via hydroxylation followed by subsequent glucuronide or sulfate conjugation. CYP isoenzymes 1A2, 2D6, and 3A4 are involved; role of CYP2D6 is relatively minor.

Exhibits nonlinear pharmacokinetics, possibly due to saturation of hepatic metabolism.

Elimination Route

<5% of a dose is excreted unchanged in urine.

Half-life

Adults: Approximately 3–3.5 hours after single 8-mg oral dose; approximately 4 hours after IV administration.

Children and adolescents 3–18 years of age: 2.4–3 hours after IV administration.

Infants 5–24 months of age: 2.9 hours after IV administration.

Infants 1–4 months of age: 6.7 hours after IV administration.

Special Populations

In patients with mild to moderate hepatic impairment, clearance is decreased 2-fold and half-life increased to 11.6 hours. In patients with severe hepatic impairment (Child-Pugh score ≥10), clearance is decreased 2- to 3-fold and half-life increased to 20 hours.

Although renal clearance contributes minimally to overall clearance, mean plasma clearance is reduced by about 50% in patients with severe renal impairment (Cl_cr <30 mL/minute); reduction in clearance is variable and not consistent with an increase in half-life.

In geriatric patients >75 years of age, clearance is decreased and half-life is increased to 4.5–6.2 hours.

Pharmacokinetics similar in poor and in extensive metabolizers of CYP2D6 substrates.

Stability

Storage

Oral

Conventional Tablets

Tight, light resistant containers at 2–30°C; protect from light.

Orally Disintegrating Tablets

2–30°C.

Solution

15–30°C; store bottles upright and protect from light.

Parenteral

Injection

2–30°C; protect from light.

Occasionally precipitates at the stopper/vial interface in vials stored upright; potency and safety not affected. If precipitate is found, vigorously shake vial to resolubilize.

Compatibility

Parenteral

Do not mix with solutions for which physical and chemical compatibility have not been established, particularly alkaline solutions, as precipitate may form.

Solution Compatibility

Drug Compatibility

Actions

• Antiemetic activity appears to be mediated both centrally (in medullary chemoreceptor trigger zone) and peripherally (in GI tract) via inhibition of 5-HT₃ receptors.

• For patients taking orally disintegrating tablets, importance of not removing tablet from blister until just before administering dose and of not pushing tablet through foil; importance of opening blister pack with dry hands and of placing tablet on tongue to dissolve and be swallowed with saliva.

• Risk of QT-interval prolongation and torsades de pointes. Importance of seeking immediate medical care if feelings of faintness, lightheadedness, irregular heartbeat, shortness of breath, or dizziness occur.

• Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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Frequently asked questions

• Can you take ondansetron while pregnant?

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