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

Maximum Dose of Ondansetron (Zofran)

The maximum recommended dose of ondansetron is 24 mg per day for oral administration and 16 mg as a single IV dose, with a daily maximum of 32 mg via any route, though the FDA label specifically states that the maximum recommended human oral dose is 24 mg per day. 1

Critical Dosing Limits by Route

Oral Administration:

• Maximum daily dose: 24 mg per day 1
• This limit is based on FDA labeling and toxicology studies showing this as the maximum recommended human oral dose 1

Intravenous Administration:

• Maximum single IV dose: 16 mg 2, 3
• Maximum daily IV dose: 32 mg 3
• The 16 mg single-dose limit exists due to cardiac safety concerns, specifically QT prolongation risk 2, 3

Context-Specific Maximum Dosing

Highly Emetogenic Chemotherapy:

• The National Comprehensive Cancer Network recommends 16-24 mg orally once daily or 8-24 mg IV once daily, with an absolute maximum of 32 mg/day 3
• A single 24 mg oral dose was studied and found effective, though this represents the upper limit 1

Moderate Emetogenic Chemotherapy:

• Standard dosing is 8 mg twice daily (16 mg total daily), which is well below the maximum 3

Breakthrough/Rescue Dosing:

• The American Society of Clinical Oncology recommends titrating up to a maximum of 16 mg oral or IV daily for breakthrough symptoms 4, 2

Important Safety Caveats

Cardiac Considerations:

• Single IV doses exceeding 16 mg carry increased risk of QT prolongation and should be avoided 2, 3
• The National Comprehensive Cancer Network specifically warns against exceeding the 16 mg single IV dose limit 3

Hepatic Impairment:

• In patients with severe hepatic impairment (Child-Pugh score ≥10), clearance is reduced 2-3 fold and half-life increases to 20 hours, necessitating dose reduction to a maximum of 8 mg per day 1

Chronic Daily Use:

• For chronic conditions like IBS with diarrhea, the British Society of Gastroenterology recommends a maximum of 8 mg three times daily (24 mg total), which aligns with the FDA maximum 5

Deprecated Regimens:

• The FDA label explicitly states that dosage regimens of 8 mg twice daily and 32 mg once daily are NOT recommended for highly emetogenic chemotherapy, despite the 32 mg dose being within the theoretical maximum 1
• This recommendation was based on efficacy data showing no advantage over 24 mg dosing 1

Practical Algorithm for Maximum Dosing

For acute chemotherapy-induced nausea:

• Start with 8 mg IV or oral, repeat every 8-12 hours as needed, not exceeding 24 mg/day oral or 32 mg/day IV 4, 2, 3

For refractory symptoms:

• Titrate to maximum 16 mg oral or IV daily, then add agents from different drug classes (dopamine antagonists, dexamethasone) rather than exceeding ondansetron maximum 4, 2

For chronic daily use:

• Maximum 8 mg three times daily (24 mg total) with monitoring for constipation and QT prolongation 5