What is the recommended pediatric dose of ondansetron (Zofran) for nausea and vomiting, including maximum single dose, formulation options, age restrictions, and contraindications?

Ondansetron (Zofran) Pediatric Dosing

For pediatric patients, administer ondansetron at 0.15 mg/kg per dose (maximum 16 mg per single dose) via oral, intravenous, or intramuscular routes, with use approved for children ≥6 months of age. 1, 2

Standard Weight-Based Dosing

• IV/IM route: 0.15 mg/kg per dose, maximum 16 mg per single dose 1, 2
• Oral route: Same weight-based dosing applies (0.15 mg/kg, maximum 16 mg) 1
• Frequency: Can be administered every 8 hours if needed, though single-dose therapy is often sufficient for acute vomiting 1
• Maximum daily doses: Typically limited to 2-3 doses in 24 hours for infants and children 1

Age Restrictions

• Minimum age: ≥6 months for acute gastroenteritis management 2
• Standard pediatric range: Children 2-12 years use the same weight-based dosing of 0.15 mg/kg (maximum 16 mg) 1
• The Infectious Diseases Society of America formally recommends ondansetron for children >4 years, though it is commonly used off-label in younger children with evidence support 3, 2

Formulation Options

• Oral disintegrating tablets: Available and convenient for children who may have difficulty swallowing 4
• Oral suspension: Available at 6 mg/mL concentration (e.g., 3 mg = 0.5 mL), can be administered without regard to meals, though food may improve GI tolerability 1
• Injectable: For IV or IM administration when oral route fails or in moderate-to-severe presentations 2

Dose-Response Considerations

Within the dose range of 0.13-0.26 mg/kg, higher doses of ondansetron were not superior to lower doses, nor were they associated with increased side effects, supporting the standard 0.15 mg/kg recommendation 4. The American Academy of Pediatrics emphasizes that ondansetron should not be rounded further when calculating doses, reflecting its narrow therapeutic considerations 5.

Critical Contraindications and Safety Warnings

Cardiac Screening Required

• Screen for cardiac history before administration: Assess for congenital heart disease, arrhythmias, or QT prolongation syndromes 2
• Special caution warranted in children with underlying heart disease due to ondansetron's potential to prolong the QT interval 1, 3, 2
• Avoid concurrent use with other QT-prolonging medications (certain antibiotics, antiarrhythmics) to minimize adverse cardiac effects 1

Hepatic Impairment

• In severe hepatic impairment, do not exceed 8 mg total daily dose 3
• Monitor for hepatotoxicity if multiple medications are being used 3

Electrolyte Monitoring

• Ensure adequate hydration before or during ondansetron administration 3
• Monitor electrolytes, particularly potassium and magnesium, as abnormalities can exacerbate QT prolongation risk 3

Context-Specific Applications

Acute Gastroenteritis

• Single-dose ondansetron produces a 41% higher chance of vomiting cessation within 8 hours compared to placebo 1
• Reduces oral rehydration therapy failure by 57% and IV hydration needs by 56% 1
• Ondansetron facilitates oral rehydration therapy, which remains the mainstay of gastroenteritis treatment 3, 2
• Antiemetic treatment should not replace appropriate fluid and electrolyte therapy 3, 2

Chemotherapy-Induced Nausea/Vomiting

• High-emetic-risk chemotherapy: Three-drug combination of ondansetron + dexamethasone + aprepitant 1, 3
• Moderate-emetic-risk chemotherapy: Two-drug combination of ondansetron + dexamethasone 1, 3
• Low-emetic-risk chemotherapy: Ondansetron monotherapy 1, 3
• The addition of dexamethasone significantly improves antiemetic efficacy in chemotherapy settings 1

Radiation-Induced Nausea/Vomiting

• 3 mg oral or IV once daily before radiation therapy, continue daily on treatment days 1

Clinical Efficacy Evidence

High-quality evidence demonstrates that ondansetron is superior to placebo and domperidone for pediatric gastroenteritis 6, 7. In children receiving cisplatin, 40% had ≤2 emetic episodes with ondansetron 1. Ondansetron reduces hospitalization rates within 8 hours (RR 0.49) and intravenous hydration needs (RR 0.44) compared to placebo 6.

Common Pitfalls to Avoid

• Do not use ondansetron as a substitute for rehydration: It should be used alongside rehydration efforts, not instead of them 3, 2
• Do not overlook cardiac screening: Always assess for underlying heart disease before administration 2
• Do not exceed maximum single dose: The 16 mg maximum per dose must be respected regardless of weight 1
• Do not round doses liberally: Ondansetron requires precise dosing without further rounding 5