What is the recommended dosing of ondansetron (Zofran) for a patient undergoing chemotherapy, radiation therapy, or surgery, considering factors such as age, weight, impaired renal function, and liver disease?

Ondansetron Dosing Recommendations

For adults undergoing chemotherapy, administer ondansetron 8 mg IV or orally 30 minutes before treatment, with dosing frequency and duration adjusted based on emetogenic risk: 8 mg every 8 hours for highly emetogenic regimens (continued 2-3 days post-chemotherapy), 8 mg twice daily for moderately emetogenic regimens (continued 1-2 days post-chemotherapy), and always combine with dexamethasone 12-20 mg for enhanced efficacy. 1, 2

Standard Dosing by Clinical Context

Highly Emetogenic Chemotherapy (e.g., Cisplatin ≥50 mg/m²)

• Initial dose: 24 mg orally as a single dose OR 8-16 mg IV, administered 30 minutes before chemotherapy 3
• Alternative regimen: 8 mg IV followed by 8 mg at 4 and 8 hours after first dose 1
• Days 2-3: Continue 8 mg orally twice daily 1, 2
• Mandatory combination: Add NK1 receptor antagonist (aprepitant/fosaprepitant) plus dexamethasone 12-20 mg IV on day 1 1, 2
• Complete response rate: 92% with ondansetron plus dexamethasone versus 41% with ondansetron alone 4

Moderately Emetogenic Chemotherapy

• Day 1: 8 mg orally or IV 30 minutes before chemotherapy, then 8 mg at 8 hours after first dose 3
• Days 2-3: 8 mg orally twice daily (every 12 hours) for 1-2 days after completion 3
• Combination therapy: Add dexamethasone 12 mg for enhanced efficacy (81% complete protection versus 64% with ondansetron alone) 1, 4

Low Emetogenic Chemotherapy

• Day 1 only: 8 mg orally twice daily or 8 mg IV 1
• No routine prophylaxis needed after day 1 2

Radiation Therapy Dosing

Total Body Irradiation

• 8 mg orally or IV administered 1-2 hours before each fraction daily 3

Single High-Dose Fraction to Abdomen

• 8 mg administered 1-2 hours before radiation 3
• Continue 8 mg every 8 hours for 1-2 days after completion 3

Daily Fractionated Radiotherapy to Abdomen

• 8 mg administered 1-2 hours before each radiation session 3
• Continue 8 mg every 8 hours on each day radiation is given 3

Postoperative Nausea and Vomiting

• 16 mg orally administered 1 hour before induction of anesthesia 3

Pediatric Dosing (Moderately Emetogenic Chemotherapy)

Ages 12-17 Years

• Same as adult dosing: 8 mg 30 minutes before chemotherapy, then 8 mg at 8 hours, followed by 8 mg twice daily for 1-2 days 3

Ages 4-11 Years

• 4 mg 30 minutes before chemotherapy 3
• 4 mg at 4 and 8 hours after first dose 3
• 4 mg three times daily for 1-2 days after completion 3

Special Population Adjustments

Severe Hepatic Impairment (Child-Pugh ≥10)

• Maximum total daily dose: 8 mg regardless of route 3
• No dosage adjustment needed for mild-moderate hepatic impairment 5

Renal Impairment

• No dosage adjustment required as ondansetron undergoes primarily hepatic metabolism (95%), with less than 10% renal excretion 5, 6

Elderly Patients

• No dosage adjustment required despite slightly reduced clearance and increased bioavailability 5

Maximum Dosing Parameters

Critical Safety Limits

• Maximum single IV dose: 16 mg (due to QT prolongation risk) 1, 3
• Maximum single oral dose: 24 mg 1, 3
• Maximum total daily dose: 32 mg by any route 1, 3

Breakthrough/Rescue Dosing

Initial Rescue Approach

• 16 mg orally or IV as single PRN dose for breakthrough nausea 1
• Can repeat every 4-6 hours as needed, not exceeding 24 mg in 24 hours 1

Refractory Nausea Management

• Add medications with different mechanisms rather than increasing ondansetron frequency 1, 7
• First-line additions: Metoclopramide 10-20 mg IV/PO every 6-8 hours OR prochlorperazine 10 mg IV/PO every 6 hours 1, 7
• Second-line additions: Dexamethasone 8-12 mg IV/PO OR lorazepam 0.5-2 mg every 4-6 hours for anticipatory nausea 1, 7
• Switch to scheduled dosing (around-the-clock for 24-48 hours) if breakthrough symptoms persist 7

Inpatient Continuous Infusion (Severe Refractory Cases)

• 8 mg IV bolus followed by 1 mg/hour continuous infusion 2

Critical Prescribing Considerations

Cardiac Safety Monitoring

• ECG monitoring required in patients with electrolyte abnormalities (hypokalemia, hypomagnesemia), congestive heart failure, bradyarrhythmias, or concomitant QT-prolonging medications 1, 3
• Avoid in congenital long QT syndrome 3
• Single IV doses exceeding 16 mg are contraindicated due to documented QT prolongation and Torsade de Pointes risk 1, 3

Drug Interactions

• Contraindicated with apomorphine due to risk of profound hypotension and loss of consciousness 3
• Reduce corticosteroid dose by 50% when combining ondansetron with aprepitant (NK1 antagonist) due to CYP3A4 interactions 1
• Monitor for serotonin syndrome when used with SSRIs, SNRIs, MAOIs, fentanyl, tramadol, or IV methylene blue 3

Common Pitfalls to Avoid

• Ondansetron monotherapy is insufficient for moderate-to-high emetogenic chemotherapy; always combine with dexamethasone 1, 2
• Constipation is common (can worsen nausea if not addressed); consider prophylactic bowel regimen 7, 4
• Simply re-dosing ondansetron too soon is less effective than adding agents with different mechanisms (ondansetron half-life is 3.5-4 hours) 7, 5
• For immunotherapy patients: Exercise caution with concomitant corticosteroid use as it may attenuate immunotherapy benefits 1

Administration Timing

• Administer at least 30 minutes before chemotherapy for optimal effect (peak plasma concentration occurs 0.5-2 hours after oral ingestion) 1, 5
• Bioavailability is 60% for oral versus IV route due to hepatic first-pass metabolism 5

Route Selection

• Oral route preferred for routine prophylaxis 2
• IV route indicated if patient has active nausea and vomiting 2
• Oral dissolving tablets (ODT) and oral soluble film available in 4 mg and 8 mg doses 1