What is the FDA approved age-based safety and dosing for ondansetron (Zofran) in neonates?

FDA Approved Age-Based Safety and Dosing for Ondansetron (Zofran) in Neonates

Ondansetron is not FDA approved for use in neonates, though it may be used off-label with caution at a dose of 0.15 mg/kg IV for treatment of vomiting in neonates when benefits outweigh risks. 1

Current FDA Approval Status

The FDA-approved package insert for ondansetron injection indicates:

• FDA approval for prevention of nausea and vomiting associated with emetogenic cancer chemotherapy and postoperative nausea/vomiting
• Specific dosing is provided for adults and pediatric patients 6 months of age and older
• No FDA-approved dosing exists specifically for neonates 1

Off-Label Dosing Recommendations for Neonates

When clinical necessity warrants off-label use in neonates, the following dosing has been used:

• IV administration: 0.15 mg/kg per dose (maximum 16 mg) 2
• Dilution in 5% Dextrose Injection or 0.9% Sodium Chloride Injection is required before administration 1

Safety Considerations in Neonates

Several important safety considerations must be taken into account when using ondansetron in neonates:

1. QT Prolongation Risk: Ondansetron can cause dose-dependent QT prolongation with potential for Torsade de Pointes. Special caution is warranted in neonates with congenital heart disease 3, 1

2. Hepatic Function: Neonates may have immature hepatic function, potentially affecting ondansetron metabolism. For patients with severe hepatic impairment, total daily dose should not exceed 8 mg 1

3. Pharmacokinetics: Research indicates that ondansetron has a longer elimination half-life in neonates compared to their mothers, suggesting potential for drug accumulation with repeated dosing 4

4. Adverse Effects: Potential adverse effects include:

   • Hypersensitivity reactions including anaphylaxis
   • Serotonin syndrome (particularly with concomitant serotonergic drugs)
   • Masking of progressive ileus and/or gastric distention 1

Clinical Applications in Neonates

While not FDA approved, ondansetron has been studied or used in neonates for:

• Management of severe vomiting episodes 3
• Prevention of neonatal abstinence syndrome 4

For neonatal abstinence syndrome, research suggests a potential dosing regimen of 0.04 mg/kg IV for neonates whose mothers did not receive ondansetron before cord clamping 4.

Monitoring Recommendations

When administering ondansetron to neonates:

• Monitor vital signs closely
• Observe for QT prolongation if ECG monitoring is available
• Watch for signs of serotonin syndrome
• Monitor for adequate hydration status
• Be prepared to provide respiratory support if needed

Contraindications

Ondansetron is contraindicated in:

• Patients with known hypersensitivity to ondansetron or other 5-HT3 receptor antagonists
• Concomitant use with apomorphine 1

While ondansetron is commonly used in pediatric patients and has an excellent safety profile at recommended doses, its use in neonates should be approached with caution and reserved for situations where the potential benefits outweigh the risks.