What is the recommended dose and administration schedule for intravenous (IV) Zofran (ondansetron)?

IV Ondansetron Administration: Dosing and Guidelines

For IV ondansetron administration, the standard dose is 8 mg (or 0.15 mg/kg, maximum 16 mg per dose) infused over 15 minutes, with specific regimens determined by the clinical indication and emetogenic risk. 1

Standard IV Dosing by Clinical Scenario

Chemotherapy-Induced Nausea and Vomiting

High Emetogenic Risk Chemotherapy:

• Administer 8-16 mg IV once on Day 1, beginning 30 minutes before chemotherapy 2, 3
• Alternative dosing: 0.15 mg/kg per dose for 3 doses (given at 0,4, and 8 hours after first dose), maximum 16 mg per dose 1
• Must be combined with dexamethasone 12 mg and an NK1 receptor antagonist (aprepitant/fosaprepitant) for optimal efficacy—ondansetron monotherapy is inadequate 4, 2, 3
• Continue antiemetic coverage for 2-3 days post-chemotherapy 2

Moderate Emetogenic Risk Chemotherapy:

• Administer 8 mg IV beginning 30 minutes before chemotherapy 4, 2, 3
• Alternative: 0.15 mg/kg IV (maximum 16 mg) 1
• Should be combined with dexamethasone 8-12 mg for enhanced efficacy 4, 2, 3
• Continue for 1-2 days after chemotherapy completion 2

Low Emetogenic Risk Chemotherapy:

• Administer 8 mg IV on the day of chemotherapy only 2, 3
• No subsequent day dosing typically required 2, 3

Postoperative Nausea and Vomiting

• Administer 4 mg IV undiluted over 2-5 minutes immediately before anesthesia induction or postoperatively 1
• For patients >40 kg: 4 mg IV single dose 1
• Dilution is not required for postoperative nausea prophylaxis 1

Radiation-Induced Nausea and Vomiting

High-Risk Radiation:

• Administer 8 mg IV before each radiation fraction 2, 3
• Continue daily on radiation days plus 1-2 days after completion 2, 3
• Combine with dexamethasone 4 mg 3

Critical Administration Requirements

Preparation and Dilution

For chemotherapy-induced nausea:

• Ondansetron injection must be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration 1
• For pediatric patients 6 months to 1 year or ≤10 kg: may dilute in 10-50 mL based on fluid needs 1
• Infuse over 15 minutes 1

For postoperative nausea:

• No dilution required—administer undiluted over 2-5 minutes 1

Stability and Compatibility

• After dilution, do not use beyond 24 hours 1
• Compatible with 0.9% Sodium Chloride, 5% Dextrose, and combination solutions for 48 hours at room temperature 1
• Do not mix with alkaline solutions as precipitation may occur 1
• Inspect for particulate matter and discoloration before administration; discard if present 1

Breakthrough/Rescue Dosing

If nausea persists despite scheduled ondansetron:

• Administer 8-16 mg IV as a single PRN dose 2, 5
• Can repeat every 4-6 hours as needed, not exceeding 24 mg in 24 hours 2
• Add medications with different mechanisms (metoclopramide 10 mg IV every 4-6 hours or prochlorperazine 10 mg IV every 4-6 hours) rather than simply increasing ondansetron frequency 2
• Consider adding dexamethasone if not already prescribed 2

For inpatients with refractory symptoms:

• 8 mg IV bolus followed by 1 mg/hour continuous infusion 5

Maximum Dosing and Safety Limits

• Maximum single IV dose: 16 mg (due to QT prolongation risk) 2, 3
• Maximum daily dose: 32 mg via any route 3, 1
• Single IV doses exceeding 16 mg are associated with increased cardiac safety concerns 2

Special Population Dosing

Severe Hepatic Impairment (Child-Pugh ≥10):

• Maximum daily dose: 8 mg IV infused over 15 minutes, beginning 30 minutes before chemotherapy 1
• No experience beyond first-day administration in this population 1

Elderly Patients:

• No dosage adjustment required despite decreased clearance and increased bioavailability 6
• Standard adult dosing applies 3

Critical Prescribing Pitfalls

Avoid these common errors:

• Never use ondansetron monotherapy for moderate-to-high emetogenic chemotherapy—combination therapy is mandatory 2, 3
• Do not exceed 16 mg as a single IV dose 2, 3
• Always administer at least 30 minutes before chemotherapy 4, 2, 1
• For immunotherapy patients, minimize concomitant corticosteroid use as it may attenuate immunotherapy benefits 2
• When combining with aprepitant, reduce corticosteroid dose by 50% due to CYP3A4 interactions 2

Pharmacokinetic Considerations

• Elimination half-life: approximately 3.8 hours 6
• Clearance occurs primarily by hepatic metabolism (95%) rather than renal excretion 6
• Peak plasma concentrations occur 6-20 minutes after IV dose 7
• Volume of distribution: approximately 160L with 70-76% protein binding 6