What is the recommended dosage of Zofran (ondansetron) for treating nausea and vomiting?

Ondansetron (Zofran) Dosing Recommendations

For chemotherapy-induced nausea and vomiting, administer ondansetron 8 mg intravenously 30 minutes before chemotherapy, or 24 mg orally as a single dose for highly emetogenic regimens, with continuation of 8 mg orally every 12 hours for delayed symptoms. 1, 2

Intravenous Dosing

• Standard IV dose is 8 mg administered over 15 minutes, given 30-60 minutes before chemotherapy initiation 1, 2
• For highly emetogenic chemotherapy (cisplatin ≥50 mg/m²), combine the 8 mg IV dose with dexamethasone 12 mg and aprepitant 125 mg on day 1 for optimal control, achieving 73-86% complete response rates 1
• If active nausea and vomiting are already present, use the intravenous route rather than oral 2
• For breakthrough nausea in hospitalized patients, consider 8 mg IV bolus followed by 1 mg/hour continuous infusion 1

Oral Dosing

Highly Emetogenic Chemotherapy

• Administer 24 mg orally as a single dose 30 minutes before chemotherapy 3
• This single 24 mg dose resulted in 66% of patients completing 24 hours with zero emetic episodes and no rescue medications 3
• The 24 mg single dose was superior to 8 mg twice daily (55% efficacy) for highly emetogenic regimens 3
• Do not use 8 mg twice daily or 32 mg once daily regimens for highly emetogenic chemotherapy - these are not recommended 3

Moderately Emetogenic Chemotherapy

• Administer 8 mg orally 30 minutes before chemotherapy, followed by 8 mg eight hours later, then 8 mg twice daily for 2 days after chemotherapy completion 2, 3
• This regimen achieved 61% complete control (zero emetic episodes) in cyclophosphamide-doxorubicin regimens 3, 4
• The twice-daily regimen is as effective as three-times-daily dosing and improves compliance 3, 4

Delayed Nausea and Vomiting

• Continue ondansetron 8 mg orally every 12 hours for 2-3 days after chemotherapy completion 1
• For oral CMF regimens (cyclophosphamide, methotrexate, 5-fluorouracil), administer 8 mg three times daily for up to 15 days, which achieved 60% complete emesis control 5

Radiation-Induced Nausea

• For radiation to the upper abdomen or total body irradiation, administer 8 mg orally 2-3 times daily during treatment 1
• This achieved complete emesis control in 67% of patients versus 45% with placebo 1

Breakthrough and Refractory Nausea

• For breakthrough symptoms despite prophylaxis, add medications from different classes such as metoclopramide (5-20 mg orally every 6-8 hours) or prochlorperazine (5-10 mg orally every 6 hours) 1, 6
• For refractory cases, consider adding lorazepam for anticipatory nausea or switching to alternative 5-HT3 antagonists like granisetron or palonosetron 1
• Add dexamethasone 4 mg orally for persistent symptoms 6

Medication-Induced Nausea (Non-Chemotherapy)

• For general medication-induced nausea, use 8 mg orally as needed (prn) rather than scheduled dosing 6
• If symptoms persist, switch to scheduled 8 mg twice daily or add an agent from a different class 6

Critical Safety Considerations

• Avoid the 32 mg IV single dose - QT interval prolongation is a concern with high-dose ondansetron, though standard 8 mg doses carry minimal risk 1
• When combining with aprepitant, reduce dexamethasone dose by 40-50% due to drug interactions 1
• Before treating breakthrough emesis, assess for non-chemotherapy causes including electrolyte abnormalities, brain metastases, or GI abnormalities 1
• Consider antacid therapy if dyspepsia is present, as patients may confuse heartburn with nausea 1

Common Pitfalls

• Ondansetron monotherapy is insufficient for highly emetogenic chemotherapy - always combine with dexamethasone and NK₁ antagonists (aprepitant) 2
• Prophylactic administration 30-60 minutes before chemotherapy is essential; do not wait for symptoms to develop 2
• For patients with persistent symptoms, switch antiemetic classes rather than increasing ondansetron dose 1, 2