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

Maximum Dose of Ondansetron (Zofran) for Adults

The maximum single intravenous dose of ondansetron is 16 mg, and the maximum total daily dose by any route is 32 mg per 24 hours. 1, 2

Critical Dosing Limits

Single-Dose Maximum

• IV route: 16 mg maximum per single administration due to dose-dependent QT interval prolongation risk documented in FDA safety reviews 1, 2
• Oral route: 24 mg maximum per single dose 3

Daily Maximum

• 32 mg per 24 hours is the absolute ceiling regardless of route (oral, IV, or combination) 1, 2

Cardiac Safety Rationale

The 16 mg IV single-dose limit exists because:

• Single IV doses exceeding 16 mg are contraindicated due to QT prolongation risk 1
• The FDA issued specific warnings after safety reviews demonstrated increased arrhythmia risk at the previously used 32 mg IV dose 4
• Patients with electrolyte abnormalities, congestive heart failure, or concomitant QT-prolonging medications require ECG monitoring even at standard doses 1

Context-Specific Maximum Dosing

Chemotherapy-Induced Nausea (High Emetogenic Risk)

• 16-24 mg orally once daily OR 8-16 mg IV once daily on day 1 1, 2
• Must be combined with dexamethasone and NK1 receptor antagonist 1, 2
• Total daily dose still cannot exceed 32 mg 1, 2

Chemotherapy-Induced Nausea (Moderate Emetogenic Risk)

• 8 mg orally twice daily (total 16 mg/day) OR 8 mg IV 1, 2
• Should be combined with dexamethasone 1, 2

Breakthrough/Rescue Dosing

• Maximum 16 mg oral or IV as a single rescue dose 1, 2
• Can be repeated every 8 hours but total daily dose must not exceed 32 mg 1
• If nausea persists, add a dopamine antagonist (metoclopramide, prochlorperazine) rather than increasing ondansetron frequency 1, 2

Common Pitfalls to Avoid

Do not exceed 16 mg IV in a single administration – the previously used 32 mg IV bolus is now contraindicated 1, 2

Do not use ondansetron monotherapy for moderate-to-high emetogenic chemotherapy – combination with dexamethasone (and NK1 antagonist for high-risk) is mandatory for efficacy 1, 2

Do not administer doses closer than 8 hours apart when using scheduled dosing 1

Do not use the 32 mg single-dose regimen – dosage regimens of 32 mg once daily are not recommended for highly emetogenic chemotherapy 3

Special Population Adjustments

Hepatic Impairment

• Severe hepatic impairment (Child-Pugh ≥10): Maximum 8 mg per day due to 2-3 fold reduction in clearance and increased half-life to 20 hours 3

Renal Impairment

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

Elderly

• No routine dose reduction needed based on age alone 1