GENVOYA(elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide)tablets(十四)
the APR. Available data from the APR through January 2016 show no birth defects reported for elvitegravir or cobicistat, and no difference in the overall risk of major birth defects for emtricitabine compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [see DATA]. In animal studies, no adverse developmental effects were observed when the components of GENVOYA were administered separately during the period of organogenesis at exposures up to 23 and 0.2 times (rat and rabbits, respectively: elvitegravir), 1.6 and 3.8 times (rats and rabbits, respectively: cobicistat), 60 and 108 times (mice and rabbits, respectively; emtricitabine) and equal to and 53 times (rats and rabbits, respectively; TAF) the exposure at the recommended daily dosage of these components in GENVOYA [see DATA]. Likewise, no adverse developmental effects were seen when elvitegravir or cobicistat was administered to rats through lactation at exposures up to 18 times or 1.2 times, respectively, the human exposure at the recommended therapeutic dose, and when emtricitabine was administered to mice through lactation at exposures up to approximately 60 times the exposure at the recommended daily dose. No adverse effects were observed in the offspring when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of GENVOYA.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The rate of miscarriage is not reported in the APR. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.
Data
Human Data
Elvitegravir: Based on prospective reports from the APR through January 2016 of 73 exposures to elvitegravir-containing regimens during pregnancy resulting in live births (including 51 exposed in the first trimester), there have been no birth defects reported.
Cobicistat: Based on prospective reports from the APR through January 2016 of 77 exposures to cobicistat-containing regimens during pregnancy resulting in live births (including 54 exposed in the first trimester), there have been no birth defects reported.
Emtricitabine: Based on prospective reports to the APR through January 2016 of 3,155 exposures to emtricitabine-containing regimens during pregnancy resulting in live births (including 2,145 exposed in the first trimester and 1,010 exposed in the second/third trimester), there was no difference between FTC and overall birth defects compared with the background birth defect rate of 2.7% in the U.S. reference population of the MACDP. The preva lence of birth defects in live births was 2.2% (95% CI: 1.6% to 3.0%) with first trimester exposure to FTC-containing regimens and 2.1% (95% CI: 1.3% to 3.2%) with the second/third trimester exposure to emtricitabine-containing regimens.
Animal Data
Elvitegravir:
Elvitegravir was administered orally to pregnant rats (0, 300, 1000, and 2000 mg/kg/day) and rabbits (0, 50, 150, and 450 mg/kg/day) through organogenesis (on gestation days 7 through 17 and days 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with elviteg |
