Miltefosine

IMPAVIDO (miltefosine) capsules are indicated in adults and pediatric patients 12 years of age and older weighing greater than or equal to 30 kg (66 lbs) for the treatment of: • Visceral leishmaniasis caused by Leishmania donovani. • Cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis. • Mucosal leishmaniasis caused by Leishmania braziliensis. Limitations of Use: • Leishmania species studied in clinical trials evaluating IMPAVIDO were based on epidemiologic data. • There may be geographic variation in clinical response of the same Leishmania species to IMPAVIDO. • The efficacy of IMPAVIDO in the treatment of other Leishmania species has not been evaluated.

Miltefosine is an anti-leishmanial agent.

Verify pregnancy status prior to initiating IMPAVIDO in females of reproductive potential. The treatment duration is 28 consecutive days. Administer with food to ameliorate gastrointestinal adverse reactions. 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. Table 1

Pregnancy IMPAVIDO is contraindicated in patients who are pregnant. Based on animal data, miltefosine may cause fetal harm.

Embryo-Fetal Toxicity IMPAVIDO is contraindicated in patients who are pregnant. Based on animal data, miltefosine may cause fetal harm. Embryo-fetal toxicity, including death and fetal malformations, was observed in animals administered miltefosine prior to mating, during early pregnancy, and during organogenesis at doses lower than the maximum recommended human dose (MRHD). Advise females of reproductive potential of the potential risk to a fetus. Verify pregnancy status prior to initiating IMPAVIDO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during treatment with IMPAVIDO and for 5 months after the last dose.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In vitro and animal metabolism studies showed that miltefosine did not markedly induce or inhibit the activity of the major human cytochrome P450 enzymes. The potential of miltefosine to interact with drug transporters has not been evaluated. IMPAVIDO did not inhibit human cytochrome P450 enzymes in vitro. IMPAVIDO did not induce cytochrome 3A activity in rats.

Store at 20-25 °C (68-77 °F), excursions permitted to 15-30 °C (59-86 °F). Protect from moisture.