Miltefosine is an antileishmanial drug indicated in adults and adolescents ≥12 years of age weighing ≥30 kg (66 lbs) for treatment of:

• Visceral leishmaniasis due to Leishmania donovani.
• Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis.
• Mucosal leishmaniasis due to Leishmania braziliensis.

Miltefosine has demonstrated activity against Leishmania parasites and neoplastic cells primarily due to its effects on apoptosis and disturbance of lipid-dependent cell signalling pathways. Several potential antileishmanial mechanisms of action have been proposed; however, no mechanism has been definitively identified. Within the mitochondria, miltefosine inhibits cytochrome-c oxidase, leading to mitochondrial dysfunction and apoptosis-like cell death. Antineoplastic mechanisms of action are related to antileishmanial targets and include inhibition of phosphatidylcholine biosynthesis and inhibition of Akt (also known as protein kinase B), which is a crucial protein within the PI3K/Akt/mTOR intracellular signalling pathway involved in regulating the cell cycle. Animal studies also suggest it may be effective against Trypanosoma cruzi (the organism responsible for Chagas' disease), metronidazole-resistant strains of Trichomonas vaginalis, and it may have broad-spectrum antifungal activity.

Administer with food to ameliorate gastrointestinal adverse reactions.

• 30 to 44 kg: one 50 mg capsule twice daily for 28 consecutive days.
• 45 kg or greater: one 50 mg capsule three times daily for 28 consecutive days.

• Miltefosine did not inhibit human cytochrome P450 enzymes in vitro.
• Miltefosine did not induce cytochrome CYP3A activity in rats.

Adverse reactions occurring in ≥2% of patients include nausea, vomiting, diarrhea, headache, decreased appetite, dizziness, abdominal pain, pruritus, somnolence, elevated transaminases, and elevated creatinine.

Pregnancy: Miltefosine should not be used during pregnancy. A urine or serum pregnancy test should be obtained in females of reproductive potential prior to prescribing.

Nursing Mothers: Discontinue either the drug or breastfeeding depending on the importance of therapy to the mother. Breastfeeding should be avoided for 5 months after Miltefosine therapy.

Females and Males of Reproductive Potential: Advise females to use effective contraception during therapy and for 5 months after completion of therapy. Patients should be informed of reproductive toxicity observed in animal studies, and that potential effects on human fertility have not been adequately evaluated.

• Embryo-Fetal Toxicity: Do not use in pregnant women. A urine or serum pregnancy test should be performed prior to initiation of therapy. Effective contraception should be advised for females of reproductive potential.
• Reproductive effects: Miltefosine caused testicular atrophy and impaired fertility in male rats, and impaired fertility in female rats. Patients should be informed of reproductive toxicity seen in animal studies and that effects on human fertility have not been adequately established.
• Renal Effects: Serum creatinine should be monitored during therapy and for 4 weeks after completion of therapy.
• Hepatic Effects: Transaminases and bilirubin should be monitored during therapy.
• Gastrointestinal Effects: Adequate fluid intake should be encouraged.
• Thrombocytopenia: Platelet count should be monitored during therapy for visceral leishmaniasis.
• Absorption of Oral Contraceptives: Alternative contraceptive methods should be used if vomiting and/or diarrhea occur.
• Stevens-Johnson Syndrome: Miltefosine should be discontinued if Stevens-Johnson syndrome develops.

Leishmaniacides

Store below 30°C, protect from light and moisture. Keep out of the reach of children.