What is the recommended dosage of miltefosine (Impavido) for pediatric patients?

Miltefosine Dosage in Pediatric Patients

For pediatric patients with leishmaniasis, miltefosine should be dosed at 2.5 mg/kg/day for 28 consecutive days, with specific weight-based dosing: children aged 2-11 years receive 2.5 mg/kg/day; patients ≥12 years weighing <25 kg receive 50 mg daily; patients ≥12 years weighing 25-44 kg receive 50 mg twice daily; and patients ≥12 years weighing ≥45 kg receive 150 mg daily in divided doses. 1

Age and Weight-Based Dosing Algorithm

Children 2-11 years:

• Target dose: 2.5 mg/kg/day for 28 days
• Note: This is off-label use in the United States for children <12 years 1
• Clinical trials have shown 88-90% cure rates with this dosing in visceral leishmaniasis 2, 3

Adolescents ≥12 years and adults:

• Weight <25 kg: 50 mg once daily for 28 days
• Weight 25-44 kg: 50 mg twice daily (100 mg/day) for 28 days
• Weight ≥45 kg: 150 mg daily in divided doses (typically 50 mg three times daily) for 28 days 1, 4

Important Clinical Considerations

Efficacy Concerns in Children

• Young children (2-11 years) have demonstrated lower cure rates and plasma drug exposures compared to adults in clinical trials 1
• This may be due to different pharmacokinetic characteristics in children 1
• Recent research suggests allometric dosing based on fat-free mass may improve outcomes, though clinical evaluations are still pending 1, 5

Administration Guidelines

• Administer with food to reduce gastrointestinal side effects 4
• Capsules should be swallowed whole, not chewed or broken apart 4
• Complete the full 28-day course to maximize efficacy and minimize resistance development 1

Monitoring Requirements

• Monitor for gastrointestinal adverse effects (vomiting, diarrhea, abdominal pain)
• Approximately 25% of children experience vomiting and 5-17% experience diarrhea, though these are typically mild to moderate 2, 3
• Monitor renal function as creatinine elevations ≥1.5 times baseline may occur in approximately 10% of patients 4
• Monitor liver function as transaminase elevations occur in up to half of patients 4

Potential Pitfalls and Caveats

1. Suboptimal exposure: Children may have lower plasma drug concentrations, potentially leading to treatment failure. Consider monitoring more closely in younger children 1, 5

2. Treatment adherence: The 28-day oral regimen requires strict adherence. Premature discontinuation due to rapid symptomatic improvement or gastrointestinal side effects can lead to treatment failure and potential drug resistance 1

3. Weight considerations: Patients weighing >60 kg receive <2.5 mg/kg/day using conventional dosing, which may affect efficacy 1

4. Contraindications: Miltefosine is contraindicated in pregnancy and breastfeeding women should not breastfeed during treatment and for 5 months afterward 1, 4

Recent research from a 2019 clinical trial suggests that allometric dosing may achieve higher and less variable exposure than linear dosing in Eastern African children, with a 90% cure rate and acceptable safety profile 5, 6. However, this approach has not yet been incorporated into standard guidelines and requires further evaluation.