IMPAVIDO

Clinical summary

Indications and usage 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 )] . The efficacy of IMPAVIDO in the treatment of other Leishmania species has not been evaluated. IMPAVIDO 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 ( 1 ). Cutaneous leishmaniasis due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis ( 1 ). Mucosal leishmaniasis due to Leishmania braziliensis ( 1 ). Limitations of use : Leishmania species evaluated in clinical trials were based on epidemiologic data. There may be geographic variation in the response of the same Leishmania species to IMPAVIDO ( 1 , 14 ). The efficacy of IMPAVIDO in the treatment of other Leishmania species has not been evaluated. Dosage and administration 2 DOSAGE AND ADMINISTRATION The treatment duration is 28 consecutive days. Administer with food to ameliorate gastrointestinal adverse reactions. Table 1: Miltefosine Dosage Weight Dosage and Administration 30 kg to 44 kg One 50 mg capsule twice daily with food (breakfast and dinner) 45 kg or greater One 50 mg capsule three times daily with food (breakfast, lunch, and dinner) Administer with food to ameliorate gastrointestinal adverse reactions. 30 to 44 kg: one 50 mg capsule twice daily for 28 consecutive days ( 2 ). 45 kg or greater: one 50 mg capsule three times daily for 28 consecutive days ( 2 ). Warnings and cautions 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. Encourage fluid intake ( 5.5 ). Thrombocytopenia. Monitor platelet count during therapy for visceral leishmaniasis ( 5.6 , 6.1 ). Absorption of Oral Contraceptives. Advise use of alternative method of contraception if vomiting and/or diarrhea occur ( 5.7 ). Stevens-Johnson syndrome. Discontinue IMPAVIDO ( 5.8 ). 5.1 Embryo-Fetal Toxicity Miltefosine may cause fetal harm. Embryo-fetal toxicity, including death and teratogenicity, 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). Do not use IMPAVIDO in pregnant women. Obtain a urine or serum pregnancy test prior to prescribing IMPAVIDO to females of reproductive potential. Advise females of reproductive potential to use effective contraception during IMPAVIDO therapy and for 5 months after completion of therapy [see Boxed Warning , Contraindications ( 4.1 ) and Use in Specific Populations ( 8.1 , 8.8 )] . 5.2 Reproductive Effects Females Miltefosine caused impaired fertility in rats and reversible follicular atresia and diestrus in dogs at doses approximately 1.0 and 0.2 times respectively the MRHD based on body surface area comparisons [see Nonclinical Toxicology ( 13.1 )] . Effects on human female fertility have not been formally studied. Males Miltefosine caused reduced viable sperm counts and impaired fertility in rats at doses approximately 0.4 times the MRHD [see Nonclinical Toxicology ( 13.1 ) ] . A higher dose in rats, approximately 1.0 times the MRHD, caused testicular atrophy and impaired fertility that did not fully reverse 10 weeks after drug administration ended. Scrotal pain and decreased or absent ejaculation during therapy have been reported during IMPAVIDO therapy [see Adverse Reactions ( 6.2 ) ] . The effects of IMPAVIDO on human male fertility have not been adequately studied. Advise women and men of the animal fertility findings, and that the potential for impaired fertility with IMPAVIDO t