Miltefosine

⛔ FDA Black Box Warning

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. Females of reproductive potential should be advised to use effective contraception during IMPAVIDO therapy and for 5 months after therapy [see Contraindications ( 4.1 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.1 , 8.8 ) and Nonclinical Toxicology ( 13.1 )] . WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. 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. Advise females of reproductive potential to use effective contraception during therapy and for 5 months after therapy ( 4.1 , 5.1 , 8.1 , 8.8 , 13.1 ).

Contraindications

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 )] . 4.2 Sjögren-Larsson-Syndrome IMPAVIDO is contraindicated in patients who have Sjögren-Larsson-Syndrome [see Clinical Pharmacology ( 12.3 )] . 4.3 Hypersensitivity IMPAVIDO is contraindicated in patients who are hypersensitive to miltefosine or any IMPAVIDO excipients.

Pregnancy & Breastfeeding

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. Numerous visceral and skeletal fetal malformations were observed in a fertility study in female rats administered miltefosine prior to mating through day 7 of pregnancy at doses 0.3 times the MRHD. Do not administer IMPAVIDO to pregnant women. Clinical Considerations During pregnancy, visceral leishmaniasis may be life-threatening for the mother and may result in adverse fetal outcomes, including spontaneous abortion, congenital disease due to vertical transmission, small for gestational age newborn, and severe anemia. During pregnancy, cutaneous leishmaniasis may manifest with larger and atypical appearing lesions and may be associated with increased risk for adverse fetal outcomes, including preterm births and stillbirths. Animal Data Miltefosine administration in rat embryo-fetal toxicity studies during early embryonic development (Day 6 to Day 15 of gestation) caused embryo-fetal toxicity including death and teratogenicity at dosages of ≥ 1.2 mg/kg/day (0.06 times the MRHD based on BSA comparison). Teratogenic effects included undeveloped cerebrum, hemorrhagic fluid filling the lumina of the skull, cleft palate and generalized edema. Embryo-fetal toxicity was also observed in rabbits after oral administration of miltefosine during organogenesis (Day 6 to Day 18 of gestation) at doses ≥ 2.4 mg/kg/day (0.2 times the MRHD based on BSA comparison). In both rats and rabbits, there were no viable litters at miltefosine doses ≥ 6.0 mg/kg/day (0.3 or 0.6 times the MRHD based on BSA comparisons for rats and rabbits respectively). In a separate fe