What is the typical dosage of Zofran (ondansetron) for adults?

Ondansetron (Zofran) Dosing for Adults

For most adult patients, ondansetron should be dosed at 8 mg orally or IV, with the specific frequency and duration determined by the clinical indication: 8 mg twice daily for moderate-risk chemotherapy, 16-24 mg once daily for high-risk chemotherapy, and 8 mg as needed for postoperative nausea. 1, 2, 3

Dosing by Clinical Indication

Chemotherapy-Induced Nausea and Vomiting

High Emetogenic Risk (e.g., cisplatin ≥50 mg/m²):

• 16-24 mg orally once daily OR 8-24 mg IV once daily (maximum 32 mg/day) 4
• Administer first dose 30 minutes before chemotherapy 3
• Continue for 2-3 days after chemotherapy completion 2
• Must be combined with dexamethasone 12 mg and NK1 receptor antagonist (aprepitant or fosaprepitant) for optimal efficacy 4, 2

Moderate Emetogenic Risk (e.g., cyclophosphamide-based regimens):

• 8 mg orally twice daily OR 8 mg IV (0.15 mg/kg) 4, 3
• First dose 30 minutes before chemotherapy 3
• Continue for 1-2 days after chemotherapy 2
• Combine with dexamethasone 8-12 mg for enhanced efficacy 4

Low Emetogenic Risk:

• 8 mg orally twice daily OR 8 mg IV on day of chemotherapy only 4, 2
• No subsequent day dosing typically required 2

Radiation-Induced Nausea and Vomiting

High Risk (total body irradiation):

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

Moderate Risk (upper abdomen, craniospinal):

• 8 mg orally or IV once daily before radiation 4
• Use as prophylaxis on radiation days only 4
• May add dexamethasone 4 mg 4

Low Risk (brain, head/neck, thorax, pelvis):

• 8 mg orally or IV as rescue therapy 4
• For brain radiation, dexamethasone 4 mg if not already prescribed 4

Postoperative Nausea and Vomiting

• 16 mg orally as a single dose, given 1 hour before induction of anesthesia 3
• Alternatively, 4 mg IV over 2-5 minutes at induction or postoperatively 5

Important Dosing Considerations

Maximum Daily Dose

• The absolute maximum is 32 mg/day via any route 4, 3
• Single IV doses should not exceed 16 mg due to cardiac safety concerns (QT prolongation risk) 2

Breakthrough/Rescue Dosing

• If nausea persists despite scheduled ondansetron, titrate up to maximum of 16 mg oral or IV daily 4, 2
• Add a dopamine antagonist (metoclopramide 10-40 mg or prochlorperazine 10 mg every 4-6 hours) from a different drug class 4, 2
• Consider adding dexamethasone if not already prescribed 2

Hepatic Impairment

• For severe hepatic impairment (Child-Pugh ≥10), maximum dose is 8 mg/day 3
• Clearance is reduced 2-3 fold and half-life increases to 20 hours 3

Renal Impairment

• No dose adjustment needed, even in severe renal impairment 3
• Renal clearance represents only 5% of total clearance 3

Available Formulations

• Oral tablets: 4 mg and 8 mg 3
• Oral dissolving tablets (ODT): 4 mg and 8 mg 2
• Oral soluble film: 8 mg 4, 2
• Injectable: 8 mg or 0.15 mg/kg IV 4, 2

Critical Prescribing Pitfalls

Avoid monotherapy for high-risk scenarios: Ondansetron alone is inadequate for highly emetogenic chemotherapy; triple therapy (ondansetron + NK1 antagonist + dexamethasone) is mandatory 4, 2. For moderate-risk chemotherapy, combination with dexamethasone is significantly superior to ondansetron alone 6.

Timing matters: Administer at least 30 minutes before chemotherapy or 1 hour before anesthesia to ensure adequate plasma levels 3, 7.

Watch for QT prolongation: The FDA removed approval for the 32 mg single IV dose due to cardiac safety concerns; use 16 mg maximum for single IV doses 2.

Constipation is common: Ensure adequate hydration and consider prophylactic stool softeners, especially in patients receiving opioids concurrently 1.

Immunotherapy caution: When prescribing for patients on immunotherapy, minimize concomitant corticosteroid use as it may attenuate immunotherapy benefits 2.