What is the recommended dose of Zofran (ondansetron) for a patient undergoing chemotherapy, radiation therapy, or surgery, considering age, weight, and renal function?

Ondansetron Dosing Recommendations

Standard Adult Dosing by Clinical Indication

For moderately emetogenic chemotherapy, administer ondansetron 8 mg orally or IV 30 minutes before chemotherapy, followed by 8 mg 8 hours later, then 8 mg twice daily (every 12 hours) for 1-2 days after chemotherapy completion. 1

Highly Emetogenic Chemotherapy

• Single 24 mg oral dose administered 30 minutes before chemotherapy (including cisplatin ≥50 mg/m²) 1
• This single-dose regimen is FDA-approved and superior to divided dosing for highly emetogenic regimens 1
• Must be combined with dexamethasone and NK1 receptor antagonist for optimal control in highly emetogenic settings 2

Moderately Emetogenic Chemotherapy

• 8 mg administered 30 minutes before chemotherapy 1
• Second dose of 8 mg given 8 hours after the first dose 1
• Continue 8 mg twice daily (every 12 hours) for 1-2 days post-chemotherapy 1
• Combination with dexamethasone 12 mg significantly improves efficacy 2

Radiation Therapy Dosing

• Total body irradiation: 8 mg administered 1-2 hours before each fraction daily 1
• Single high-dose abdominal radiation: 8 mg 1-2 hours before, then 8 mg every 8 hours for 1-2 days after completion 1
• Daily fractionated abdominal radiation: 8 mg 1-2 hours before each fraction, then 8 mg every 8 hours on treatment days 1
• May add dexamethasone 4 mg daily for enhanced control 3, 2

Postoperative Nausea/Vomiting

• 16 mg administered 1 hour before induction of anesthesia 1

Pediatric Dosing

Ages 12-17 Years

• Same as adult dosing: 8 mg before chemotherapy, 8 mg 8 hours later, then 8 mg twice daily for 1-2 days 1

Ages 4-11 Years

• 4 mg 30 minutes before chemotherapy 1
• Subsequent 4 mg doses at 4 and 8 hours after first dose 1
• Continue 4 mg three times daily for 1-2 days post-chemotherapy 1

Special Population Adjustments

Severe Hepatic Impairment (Child-Pugh ≥10)

• Maximum total daily dose: 8 mg regardless of indication 1
• No dose adjustment needed for mild-moderate hepatic impairment 1

Elderly Patients

• Start with 4 mg rather than 8 mg due to increased drug sensitivity 4
• May titrate upward if needed, but begin conservatively 4
• Elderly are particularly sensitive to adjunctive benzodiazepines (start lorazepam at 0.25 mg, maximum 2 mg/24 hours) 4

Renal Impairment

• No dose adjustment required for any degree of renal dysfunction 1, 5

Critical Safety Parameters

Maximum Dosing Limits

• Maximum single IV dose: 16 mg (due to QT prolongation risk) 2, 1
• Maximum single oral dose: 24 mg 2, 1
• Maximum total daily dose: 32 mg via any route 2

Cardiac Monitoring

• ECG monitoring required in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, bradyarrhythmias, or concomitant QT-prolonging medications 1
• Avoid in congenital long QT syndrome 1
• Single IV doses >16 mg are contraindicated due to dose-dependent QT prolongation 2, 1

Breakthrough Nausea Management

If nausea persists despite scheduled ondansetron, add medications from different drug classes rather than increasing ondansetron frequency. 2, 4

Rescue Therapy Options

• Metoclopramide 10-40 mg PO/IV every 4-6 hours PRN 3, 2
• Prochlorperazine 10 mg PO/IV every 4-6 hours PRN 3, 2
• Haloperidol 1 mg (0.5 mg in elderly) 4
• Dexamethasone 8-12 mg if not already prescribed 6

When to Escalate

• If rescue ondansetron is required, transition to prophylactic scheduled therapy for remainder of treatment 2
• For next chemotherapy cycle, escalate antiemetic regimen (e.g., add NK1 antagonist or olanzapine) 6

Common Prescribing Pitfalls

Avoid These Errors

• Do not use 8 mg three times daily regimen for moderately emetogenic chemotherapy—twice daily is equally effective and FDA-approved 1
• Do not use 8 mg twice daily or 32 mg single dose for highly emetogenic chemotherapy—only 24 mg single dose is recommended 1
• Do not prescribe ondansetron monotherapy for moderate-to-high emetogenic chemotherapy—combination with dexamethasone is mandatory 2, 6
• Do not continue ondansetron indefinitely—limit to treatment days plus 1-2 days post-treatment 6
• Avoid PRN-only dosing during active treatment—scheduled prophylactic dosing is superior 6

Drug Interactions

• Contraindicated with apomorphine (risk of profound hypotension and loss of consciousness) 1
• Reduce dexamethasone dose by 50% when combining with aprepitant (NK1 antagonist) due to CYP3A4 interactions 2
• Monitor for serotonin syndrome when used with SSRIs, SNRIs, MAOIs, tramadol, fentanyl, or methylene blue 1

Duration of Therapy

Ondansetron should only be administered during active treatment periods, not indefinitely. 6

Treatment Duration by Indication

• Moderately emetogenic chemotherapy: Day of treatment plus 1-2 days 1
• Highly emetogenic chemotherapy: Single dose on day of treatment (may extend 2-3 days if needed) 2, 1
• Radiation therapy: Daily during active radiation plus 1-2 days after completion 6, 1
• Postoperative: Single preoperative dose 1

When Nausea Persists Beyond Expected Window

• Investigate non-treatment causes: brain metastases, electrolyte abnormalities, bowel obstruction, other GI pathology 6
• Do not simply continue ondansetron—reassess diagnosis and add agents from different classes 6

Administration Timing

Administer ondansetron at least 30 minutes before chemotherapy for optimal effect (1-2 hours before radiation therapy). 2, 1

• Peak plasma concentration occurs 1 hour after oral dose 7, 5
• Bioavailability is 60% for oral formulation 7, 5
• Half-life is approximately 3.5-3.8 hours 7, 5

Available Formulations

• Oral tablets: 4 mg and 8 mg 1
• Oral dissolving tablets (ODT): 4 mg and 8 mg 2
• Oral soluble film: 8 mg 2
• Injectable: 8 mg or 0.15 mg/kg IV 2, 1
• Intramuscular: 4-8 mg (when oral/IV not feasible) 4