Miltefosine

1 INDICATIONS AND USAGE IMPAVIDO (miltefosine) capsules are indicated in adults and adolescents ≥12 years of age weighing ≥ 30 kg for the treatment of: Visceral leishmaniasis caused by Leishmania donovani [see Clinical Trials ( 14.1 )] . Cutaneous leishmaniasis caused by Leishmania braziliensis , Leishmania guyanensis , and Leishmania panamensis [see Clinical Trials ( 14.2 )] . Mucosal leishmaniasis caused by Leishmania braziliensis [see Clinical Trials ( 14.3 )] . Limitations of Use: Leishmania species studied in clinical trials evaluating IMPAVIDO were based on epidemiologic data [see Clinical Trials ( 14.1 , 14.2 )] . There may be geographic variation in clinical response of the same Leishmania species to IMPAVIDO [see Clinical Trials ( 14.1 , 14.2 )] .

6 ADVERSE REACTIONS 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. Adverse reactions occurring in ≥2% of patients include nausea, vomiting, diarrhea, headache, decreased appetite, dizziness, abdominal pain, pruritus, somnolence, elevated transaminases, and elevated creatinine (6.1). To report SUSPECTED ADVERSE REACTIONS, contact Profounda, Inc. at 1-866-588-5405 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Visceral Leishmaniasis One Phase 3 trial was conducted in patients ≥ 12 years of age in India.

8.1 Pregnancy Pregnancy Category D Risk Summary IMPAVIDO may cause fetal harm. Human pregnancy data are not available, however, embryo-fetal toxicity including death and teratogenicity, was observed in embryo-fetal studies in rats and rabbits administered oral miltefosine during organogenesis at doses that were respectively 0.06 and 0.2 times the maximum recommended human dose (MRHD), based on body surface area (BSA) comparison.

WARNING: EMBRYO-FETAL TOXICITY IMPAVIDO may cause fetal harm. Fetal death and teratogenicity occurred in animals administered miltefosine at doses lower than the recommended human dose. Do not administer IMPAVIDO to pregnant women. Obtain a serum or urine pregnancy test in females of reproductive potential prior to prescribing IMPAVIDO. 5 WARNINGS AND PRECAUTIONS Embryo-Fetal Toxicity. Do not use in pregnant women. Obtain a urine or serum pregnancy test prior to initiation of therapy. Advise use of effective contraception in females of reproductive potential ( Boxed Warning , 5.1 , 8.1 , 8.8 , 13.1 ). Reproductive effects. Miltefosine caused testicular atrophy and impaired fertility in male rats and impaired fertility in female rats. Advise patients of reproductive toxicities in animal studies and that the potential effects on human fertility have not been adequately evaluated ( 13.1 ). Renal Effects. Monitor serum creatinine during therapy and for 4 weeks after end of therapy ( 5.3 , 6.1 ). Hepatic Effects. Monitor transaminases and bilirubin during therapy ( 5.4 , 6.1 ). Gastrointestinal Effects. 4 CONTRAINDICATIONS Pregnancy ( 4.1 , 8.1 , 8.8 , 13.1 ). Sjögren-Larsson-Syndrome ( 4.2 , 12.3 ). Hypersensitivity to miltefosine or any of its excipients ( 4.3 ). 4.1 Pregnancy IMPAVIDO may cause fetal harm. IMPAVIDO is contraindicated in pregnant women. Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO [see Boxed Warning and Use in Specific Populations ( 8.1 )] .