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, 2025. Written by ASHP.

Introduction

Antiemetic; selective, first-generation inhibitor of type 3 serotonergic (5-HT₃) receptors.^{1 33 82}

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.^{1 3 6 8 10 27 28 29 30 31 33 36 37 38 39 40 41}

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.^{82 83} ASCO states that fixed-combination netupitant and palonosetron plus dexamethasone is an additional treatment option.⁸³

For moderately emetogenic chemotherapy regimens, ASCO recommends a 2-drug antiemetic regimen preferably consisting of palonosetron and dexamethasone.^{82 83} If palonosetron is not available, a first-generation 5-HT₃ receptor antagonist (preferably granisetron or ondansetron) may be substituted.⁸² Limited evidence suggests that aprepitant may be added to this regimen; in such cases, use of any 5-HT₃ receptor antagonist is appropriate.⁸²

For chemotherapy regimens with a low emetogenic risk, ASCO recommends administration of a single dose of dexamethasone prior to chemotherapy.⁸²

For chemotherapy regimens with minimal emetogenic risk, ASCO states that routine antiemetic administration is not necessary.⁸²

Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting.^{1 4 11 12 32 33 76}

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.^{1 33}

Recommended for patients who, in the clinician’s judgement, must avoid nausea and/or vomiting postoperatively, even when anticipated incidence is low.^{1 33}

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.³³

Ondansetron Dosage and Administration

Administration

Administer orally, by IV infusion, or by IV or IM injection.^{1 33}

Oral Administration

Administer orally as conventional tablet, orally disintegrating tablet, or oral solution.³³

Commercially available oral solution and orally disintegrating tablets may be used interchangeably.³³

Do not remove orally disintegrating tablet from blister until just prior to dosing; do not push through foil.³³ With dry hands, peel open blister package, and gently remove the tablet; place tablet on tongue to dissolve, and swallow with saliva.³³

Administration of orally disintegrating tablet with liquid is not necessary.³³

IV Administration

For prevention of cancer chemotherapy-induced nausea/vomiting, administer by IV infusion using diluted injection.¹

For prevention of postoperative nausea and vomiting, administer undiluted by IV injection.¹

Dilution

For IV infusion, dilute ondansetron hydrochloride injection in 50 mL of 5% dextrose injection or 0.9% sodium chloride injection.¹

For IV injection, no dilution required.¹

Rate of Administration

IV infusion: Infuse over 15 minutes.¹

IV injection: Inject over a period of ≥30 seconds, preferably over 2–5 minutes.¹

IM Administration

For prevention of postoperative nausea and vomiting in adults, may administer undiluted by IM injection as an alternative to IV injection.¹ (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.^{1 33}

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.³³ Continue with 4 mg every 8 hours for 1–2 days after completion of chemotherapy.³³

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.³³ Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.³³

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.¹

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.¹

Children ≤12 years of age weighing >40 kg: 4 mg as a single dose by IV injection immediately before or after induction of anesthesia.¹

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.¹

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.¹

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.¹

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.³³ Continue with 8 mg every 12 hours for 1–2 days after completion of chemotherapy.³³

24 mg as a single dose given 30 minutes before administration of single-day highly emetogenic chemotherapy.³³

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.¹

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.⁷⁸

Postoperative Nausea and Vomiting

Prevention

Oral

16 mg as a single dose given 1 hour before induction of anesthesia.³³

IV

4 mg as a single dose by IV injection (undiluted) immediately before induction of anesthesia.¹

Limited information available regarding dosage in patients weighing >80 kg.¹

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.¹

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.¹

IM

4 mg as a single dose by IM injection (undiluted) as an alternative to IV administration.¹

Limited information available regarding dosage in patients weighing >80 kg.¹

Radiation-induced Nausea and Vomiting

Prevention, Usual Dosage

Oral

Usually, 8 mg 3 times daily.³³

Prevention, for Total Body Irradiation

Oral

8 mg 1–2 hours before each fraction of radiotherapy administered each day.³³

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.³³

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.³³

Prescribing Limits

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

0.15 mg/kg (maximum 16 mg per dose).^{1 78} (See Cardiac Effects under Cautions.)

Adults

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

0.15 mg/kg (maximum 16 mg per dose).^{1 78} (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); ^{1 33} no experience to date with continuation beyond the first day of IV therapy.¹

Renal Impairment

No dosage adjustment required, but no experience to date with continuation beyond the first day of therapy.³³

Geriatric Patients

No dosage adjustment required.^{1 33}

Cautions for Ondansetron

Contraindications

• Known hypersensitivity to ondansetron or any ingredient in the formulation.^{1 33}

• Concomitant use with apomorphine.^{1 33} (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.^{1 5 16 33 39}

Possible hypersensitivity reactions in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.^{1 33}

Cardiac Effects

Dose-related prolongation of QT interval and cases of torsades de pointes reported.^{1 33 78 79} ECG alterations including QT-interval prolongation reported mainly with IV administration.^{1 33}

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.^{1 78} Individual IV doses should not exceed 16 mg.^{1 78} (See Dosage under Dosage and Administration.)

Avoid use of ondansetron in patients with congenital long QT syndrome.^{1 33 79}

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.^{1 33 79} Correct electrolyte abnormalities prior to IV administration of ondansetron.⁷⁸

GI Precautions

Does not stimulate gastric or intestinal peristalsis; do not use as a substitute for nasogastric suction.^{1 33}

May mask progressive ileus and/or gastric distention in patients undergoing abdominal surgery or in those with chemotherapy-induced nausea and vomiting.^{1 33}

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.³³

Specific Populations

Pregnancy

Category B.^{1 33}

Lactation

Distributed into milk in rats; not known whether distributed into human milk.^{1 33} Caution advised if used in nursing women.^{1 33}

Pediatric Use

Safety and efficacy of oral or IV ondansetron for prevention of chemotherapy-induced emesis generally comparable to that in adults.^{1 33}

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.^{1 33} Little information available on oral dosage in children ≤4 years of age.³³

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.¹ (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.³³

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.^{1 16 33}

Hepatic Impairment

Clearance is decreased and half-life increased in patients with hepatic impairment.^{1 33} Use with caution and at reduced dosage in patients with severe hepatic impairment.^{1 15 33} (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.^{1 33}

Drug Interactions

Substrate of CYP1A2, CYP2D6, and CYP3A4 in vitro; does not appear to induce or inhibit CYP isoenzymes.^{1 33}

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP1A2, CYP2D6, or CYP3A4; potential pharmacokinetic interaction (altered ondansetron metabolism).^{1 33} Based on available data, no dosage adjustment recommended for patients on these drugs.^{1 33}

Drugs that Prolong QT Interval

Potential additive effect on QT-interval prolongation.^{1 33} Monitor ECG during concomitant use.^{1 33} (See Cardiac Effects under Cautions.)

Specific Drugs

Ondansetron Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract after oral administration.³³ Mean bioavailability after administration of single 8-mg tablet is approximately 56%; increased bioavailability expected with dosages >8 mg.^{33 c}

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.^{1 33 c}

Commercially available oral solution and orally disintegrating tablets (4- or 8-mg doses) are bioequivalent to corresponding doses of conventional tablets.³³

Food

Food slightly increases bioavailability.³³

Special Populations

Extent and rate of absorption are increased in women compared with men; not known whether differences are clinically important.³³

Distribution

Extent

Circulating drug distributes into erythrocytes.³³

Distributed into milk in rats; not known whether distributed into human milk.³³

Plasma Protein Binding

70–76%.³³

Elimination

Metabolism

Extensively metabolized in the liver via hydroxylation followed by subsequent glucuronide or sulfate conjugation.³³ CYP isoenzymes 1A2, 2D6, and 3A4 are involved;^{1 33} role of CYP2D6 is relatively minor.¹

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

Elimination Route

<5% of a dose is excreted unchanged in urine.¹

Half-life

Adults: Approximately 3–3.5 hours after single 8-mg oral dose; approximately 4 hours after IV administration.^{1 33 c}

Children and adolescents 3–18 years of age: 2.4–3 hours after IV administration.^{1 c}

Infants 5–24 months of age: 2.9 hours after IV administration.¹

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

Special Populations

In patients with mild to moderate hepatic impairment, clearance is decreased 2-fold and half-life increased to 11.6 hours.^{1 33} In patients with severe hepatic impairment (Child-Pugh score ≥10), clearance is decreased 2- to 3-fold and half-life increased to 20 hours.^{1 33}

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.^{1 33}

In geriatric patients >75 years of age, clearance is decreased and half-life is increased to 4.5–6.2 hours.^{1 33}

Pharmacokinetics similar in poor and in extensive metabolizers of CYP2D6 substrates.¹

Stability

Storage

Oral

Conventional Tablets

Tight, light resistant containers at 2–30°C; protect from light.³³

Orally Disintegrating Tablets

2–30°C.³³

Solution

15–30°C; store bottles upright and protect from light.³³

Parenteral

Injection

2–30°C; protect from light.¹

Occasionally precipitates at the stopper/vial interface in vials stored upright; potency and safety not affected.¹ If precipitate is found, vigorously shake vial to resolubilize.¹

Compatibility

Parenteral

Do not mix with solutions for which physical and chemical compatibility have not been established, particularly alkaline solutions, as precipitate may form.¹

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.^{27 43 44 45 47 50 51 67 68}

• 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.³³

• Risk of QT-interval prolongation and torsades de pointes.^{1 33 78 79} Importance of seeking immediate medical care if feelings of faintness, lightheadedness, irregular heartbeat, shortness of breath, or dizziness occur.^{1 78 79}

• Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.³³

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 33}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{1 33}

• Importance of advising patients of other important precautionary information.^{1 33} (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

Frequently asked questions

• Can you take ondansetron while pregnant?

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