What is the recommended use and dosage of Miltefosine for treating parasitic infections?

Recommended Use and Dosage of Miltefosine for Parasitic Infections

For treatment of leishmaniasis, miltefosine should be administered orally at 2.5 mg/kg/day for 28 consecutive days, with a maximum dose of 150 mg daily in divided doses. 1, 2

Approved Indications and Dosing Regimens

Visceral Leishmaniasis (VL)

• Adults and children ≥12 years:
  • Weight <25 kg: 50 mg daily for 28 days
  • Weight 25-44 kg: 50 mg twice daily for 28 days
  • Weight ≥45 kg: 50 mg three times daily (150 mg total) for 28 days 1, 2
• Children 2-11 years: 2.5 mg/kg/day for 28 days 3

Cutaneous Leishmaniasis (CL)

• FDA-approved for CL caused by L. braziliensis, L. panamensis, and L. guyanensis 1
• Same dosing regimen as for visceral leishmaniasis

Mucosal Leishmaniasis (ML)

• Recommended dose: 2.5-3.3 mg/kg/day for 28-42 days 1

Administration Guidelines

• Administer with food to reduce gastrointestinal side effects 2
• Capsules should be swallowed whole, not chewed or broken 2
• Complete the full 28-day course to maximize efficacy and prevent resistance 3

Efficacy by Parasite Species and Geographic Region

Visceral Leishmaniasis

• L. donovani (Indian subcontinent): 94-97% cure rates with standard regimen 1
• L. donovani (East Africa): 75.6% cure rates 1
• L. infantum (Mediterranean/South America): Limited data available 1

Cutaneous Leishmaniasis

• L. panamensis (Colombia): 82% cure rate 2
• L. braziliensis (Brazil): 67.5-85% cure rate depending on region 2
• L. guyanensis (Brazil): 67.5% cure rate 2
• L. major (Iran): Good efficacy (specific rates not provided) 1

Combination Therapy Options

For visceral leishmaniasis in the Indian subcontinent, combination therapy may be preferred:

1. Liposomal amphotericin B (IV) 5 mg/kg single dose + miltefosine for 7-14 days 1
2. Paromomycin (IM) 15 mg/kg/day for 10 days + miltefosine for 10 days 1

Special Populations

HIV-Coinfected Patients

• Miltefosine (100 mg daily for 28 days) is safer but less effective than sodium stibogluconate for VL in HIV-infected patients 1
• Consider combination therapy with L-AmB and miltefosine for refractory cases 1

Pediatric Patients

• Children may have lower plasma drug concentrations, potentially leading to treatment failure 3
• Close monitoring recommended for children 2-11 years 3

Adverse Effects and Monitoring

• Common adverse effects: Gastrointestinal (vomiting, diarrhea, abdominal pain) 2, 4
• Less common but serious: Hepatotoxicity, nephrotoxicity 4
• Monitoring: Liver function tests, renal function tests before and during treatment 2

Important Contraindications and Precautions

• Pregnancy: Absolutely contraindicated due to teratogenic potential 2, 5
• Breastfeeding: Contraindicated during treatment and for 5 months after therapy 3, 2
• Women of reproductive potential: Must use effective contraception during therapy and for 5 months after 2
• Renal/hepatic impairment: Monitor closely; dose adjustment may be needed 2

Clinical Pearls and Pitfalls

• Resistance concerns: The long half-life of miltefosine combined with premature treatment discontinuation can lead to subtherapeutic levels and development of resistance 1
• Weight-based dosing: Patients weighing >60 kg may receive <2.5 mg/kg/day using conventional dosing, which may affect efficacy 3
• Treatment duration: Complete the full 28-day course even if symptoms improve quickly 3
• Oral contraceptives: Women using oral contraceptives should use additional non-hormonal contraception if vomiting/diarrhea occurs 2

Miltefosine represents a significant advancement in leishmaniasis treatment as the first effective oral therapy, but proper dosing, complete adherence to the treatment course, and appropriate monitoring are essential to maximize efficacy and minimize the risk of resistance development.