west bremelanotide dose associated with fetal harm has not beenidentified for either species. For this reason, women should use effective contraception while taking VYLEESI
and discontinue VYLEESI if pregnancy is suspected.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Data
Human Data
There were 7 pregnancies reported in the clinical trials of more than 1057 patients treated with VYLEESI for upto 12 months. Among these 7 pregnancies, no major congenital anomalies were reported. There was onespontaneous abortion (miscarriage), five full-term live births, and one outcome was unknown due to loss to
follow-up.
Animal Data
An embryofetal development study was conducted in the dog and a pre- and postnatal development study wasconducted in the mouse to inform developmental risk. These two species are not routinely used for reproductivetoxicity assessment but were the only two species that could be successfully dosed by the subcutaneous route
during gestation.
Bremelanotide was administered subcutaneously to pregnant dogs (8/dose) at 2, 8, or 20 mg/kg from gestationday (GD) 18-35, corresponding to the period from implantation to late embryogenesis in the dog. Embryofetaltoxicity, as measured by post-implantation loss, was elevated approximately 3 to 8-fold compared to controls
across all treated groups but was not dose-dependent. A developmental no-observed-effect level (NOEL) wasnot set. At the low dose of 2 mg/kg/day in the dog, exposure was approximately 16 times the human exposurebased on AUC.
In a pre- and postnatal development study, female mice (30/dose) were dosed subcutaneously at 0, 30, 75, and150 mg/kg/day from GD 6 through lactation day (LD) 28, and two generations of offspring were assessed (F1and F2). There were no effects on reproductive parameters in parental (F0) or F1 generation animals at doses upto 150 mg/kg/day (approximately 760 times the human AUC). However, developmental delays were observedin the F1 generation mice at ≥ 30 mg/kg/day (approximately 125 times the human AUC). For that reason, adevelopmental NOEL was not set. There were no significant effects on the growth and development of F2generation pups.
8.2 Lactation
Risk Summary
There is no information on the presence of bremelanotide or its metabolites in human milk, the effects on thebreastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinicalneed for VYLEESI and any potential adverse effects on the breastfed child from VYLEESI or from theunderlying maternal condition.
8.3 Females and Males of Reproductive Potential
Contraception
Use of VYLEESI during pregnancy is not recommended [see Use in Specific Populations (8.1)]. Advisefemales of reproductive potential to use effective contraception while taking VYLEESI, and to discontinueVYLEESI if pregnancy is suspected.
8.4 Pediatric Use
The safety and effectiveness of VYLEESI have not been established in pediatric patients.
8.5 Geriatric Use
The safety and effectiveness of VYLEESI have not been established in geriatric patients.
8.6 Renal Impairment
No dosing adjustments are recommended for patients with mild to moderate (eGFR 30-89 mL/min/1.73 m2)renal impairment. Use with caution in patients with severe (eGFR <30 mL/min/1.73 m2) renal imp |
