Miltefosine Dosing for Kala Azar (Visceral Leishmaniasis)
The recommended dose of miltefosine for treating kala azar (visceral leishmaniasis) is 2.5 mg/kg/day for 28 consecutive days, with a maximum daily dose of 150 mg. 1
Standard Dosing Regimen
- For patients weighing 30-44 kg: 50 mg twice daily (total 100 mg/day) for 28 consecutive days 1
- For patients weighing ≥45 kg: 150 mg daily (in 3 divided doses of 50 mg) for 28 consecutive days 1
- Doses should be taken with food to minimize gastrointestinal side effects 1
Special Population Considerations
Children
- FDA approval is limited to patients ≥12 years of age who weigh ≥30 kg 1
- Use in children <12 years or <30 kg is considered off-label in the United States 1
- Young children (2-11 years) may have lower plasma drug exposure and potentially lower cure rates compared to adults 1
- A dosing algorithm with nonlinear, allometric scaling based on fat-free mass has been proposed for children, though the maximum daily dose remains 150 mg 1
Pregnant and Breastfeeding Women
- Miltefosine is contraindicated in pregnancy due to potential fetotoxicity 1
- Breastfeeding women should not breastfeed during treatment or for 5 months after treatment 1
Efficacy and Treatment Outcomes
- Miltefosine has demonstrated excellent cure rates in visceral leishmaniasis in India, Nepal, and Bangladesh 1
- In Bangladesh, a phase IV trial showed an 85% cure rate using the 2.5 mg/kg/day dosing for 28 days 2
- Early studies showed that daily dosing (100-150 mg/day) was more effective than alternate-day dosing, with 18 of 19 patients on daily regimens achieving definitive cure at 8 months 3
Combination Therapy
- Combination therapy with liposomal amphotericin B has shown promising results 1
- A single dose of liposomal amphotericin B (5 mg/kg) followed by 7-14 days of miltefosine showed 96-98% cure rates 1
- Combination therapies may reduce treatment duration, decrease toxicity, and potentially reduce the development of drug resistance 1
Common Side Effects and Monitoring
- Gastrointestinal side effects are most common, with vomiting in 25% and diarrhea in 8% of patients 2
- Divided dosing is recommended to minimize gastrointestinal symptoms 1
- Monitoring for renal insufficiency is important, as severe cases have been reported 3
Special Considerations
- Patients with HIV co-infection may have lower cure rates and higher relapse rates 1
- In Ethiopia, a study showed miltefosine (100 mg/day for 28 days) was safer but less effective than sodium stibogluconate in HIV-prevalent populations 1
- For post-kala-azar dermal leishmaniasis (PKDL), longer treatment durations (60-90 days) at doses of 150 mg/day have shown 96% cure rates 4, 5
Pitfalls to Avoid
- Doses <2 mg/kg/day are associated with lower response rates 1
- Patients weighing >60 kg receive <2.5 mg/kg/day using standard dosing, which may affect efficacy 1
- Poor compliance with the full 28-day course may lead to treatment failure and potential drug resistance 1
- Contraindication in pregnancy must be strictly observed due to potential fetotoxicity 1