What is the maximum recommended dose of ondansetron (Zofran)?

Maximum Recommended Dose of Ondansetron

The maximum daily dose of ondansetron is 32 mg per day via any route, with a critical safety restriction that single intravenous doses must not exceed 16 mg due to cardiac safety concerns related to QT interval prolongation. 1, 2, 3

Key Dosing Limits by Route

Intravenous Administration

• Single IV dose maximum: 16 mg 1, 3, 4
• The FDA withdrew approval for the 32 mg single IV dose in 2012 after identifying dose-dependent QT prolongation risks that could lead to torsades de pointes, a potentially fatal arrhythmia 5, 4
• For breakthrough or rescue dosing, titrate up to a maximum of 16 mg IV daily 1, 2

Oral Administration

• Maximum single oral dose: 24 mg 5, 3
• Maximum daily oral dose: 32 mg (typically given as divided doses) 1
• Common regimens include 16-24 mg once daily or 8 mg two to three times daily, depending on emetogenic risk 5, 1

Context-Specific Maximum Dosing

Highly Emetogenic Chemotherapy

• Oral: 16-24 mg once daily (maximum 24 mg per dose) 5, 1
• IV: 8-16 mg once daily (maximum 16 mg per dose) 5, 1
• Must be combined with dexamethasone and an NK1 receptor antagonist for optimal efficacy 1

Moderately Emetogenic Chemotherapy

• Oral: 8 mg twice daily (16 mg total daily) 5, 2
• IV: 8 mg per dose 5, 2

Postoperative Nausea and Vomiting

• Single dose: 4 mg IV is optimal 6
• Maximum: 8 mg IV single dose 1

Critical Safety Considerations

Cardiac Risk Profile:

• QT prolongation is dose-dependent, with highest risk at 32 mg IV 5, 4
• Ondansetron is the only 5-HT3 receptor antagonist besides dolasetron with FDA warnings regarding cardiac safety 5
• Lower doses (≤16 mg IV) have demonstrated QT prolongation in healthy volunteers, though clinical significance remains unclear 4

Common Prescribing Pitfalls:

• Never prescribe 32 mg as a single IV dose—this formulation was withdrawn from the market 5, 3
• Avoid exceeding 16 mg IV in any single administration, even if dividing the 32 mg daily maximum into multiple doses 1, 3
• When using ondansetron for highly emetogenic chemotherapy, monotherapy is inadequate; triple therapy (ondansetron + NK1 antagonist + dexamethasone) is mandatory 1, 2

Special Population Adjustments

Hepatic Impairment

• Maximum daily dose: 8 mg in patients with severe hepatic impairment (Child-Pugh ≥10) 3
• Clearance is reduced 2-3 fold with half-life increasing to 20 hours in severe hepatic disease 3

Renal Impairment

• No dose adjustment required, as renal clearance represents only 5% of total clearance 3