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

Maximum Daily Dose of Ondansetron (Zofran)

The maximum daily dose of ondansetron is 32 mg per 24 hours via any route (oral or intravenous), and the maximum single intravenous dose is 16 mg due to QT interval prolongation risk. 1, 2, 3

Absolute Dosing Limits

• Total daily maximum: 32 mg per 24 hours regardless of administration route (oral, IV, or combination) 1, 2, 3
• Single IV dose maximum: 16 mg per administration due to dose-dependent QT prolongation documented in FDA safety reviews 1, 3
• Single oral dose maximum: 24 mg per administration 1

Cardiac Safety Rationale

The 16 mg single IV dose ceiling exists because higher doses cause QT interval prolongation. 1, 3 Patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, or concomitant QT-prolonging medications require ECG monitoring even at standard doses. 1

Context-Specific Daily Dosing

Chemotherapy-Induced Nausea (High Emetogenic Risk)

• Day 1: 16–24 mg orally once OR 8–16 mg IV once (maximum 32 mg/day total) 1, 2
• Days 2–3: 8 mg orally twice daily (16 mg/day total) 1
• Must combine with dexamethasone and NK1 antagonist—ondansetron alone is inadequate 1, 2

Chemotherapy-Induced Nausea (Moderate Emetogenic Risk)

• 8 mg orally twice daily OR 8 mg IV (16 mg/day total) 1, 2
• Continue for 1–2 days post-chemotherapy 1

Radiation-Induced Nausea

• 8 mg orally or IV 2–3 times daily (16–24 mg/day total) throughout radiation course plus 1–2 days after completion 1, 2

Postoperative Nausea

• Single 4 mg IV dose for adults; a second 4 mg dose provides no additional benefit 3

Critical Prescribing Pitfalls

• Never exceed 32 mg in 24 hours from all sources combined (oral + IV) 1, 2, 3
• Never give >16 mg as a single IV bolus—this is contraindicated per FDA labeling 1, 3
• For breakthrough nausea despite scheduled ondansetron, add a dopamine antagonist (metoclopramide 10–40 mg or prochlorperazine 10 mg) rather than increasing ondansetron frequency beyond the 32 mg/day ceiling 1, 2
• Ondansetron monotherapy fails in moderate-to-high emetogenic scenarios; combination with dexamethasone (and NK1 antagonist for high-risk) is mandatory 1, 2

Hepatic Impairment Adjustment

In severe hepatic impairment (Child-Pugh ≥10), reduce to a single 8 mg dose per day infused over 15 minutes. 3 No adjustment is needed for renal impairment or elderly patients without severe liver disease. 4