Tegrad Use In Pregnancy & Lactation

Pregnancy: Teratogenic Effects Risk: Summary: There are insufficient human data on the use of dolutegravir tablets during pregnancy to inform a drug- associated risk of birth defects and miscarriage. Given the limited number of pregnancies exposed to dolutegravir-based regimens reported to the APR, no definitive conclusions can be drawn on the safety of dolutegravir in pregnancy, and continued monitoring is ongoing through the APR. The background rate for major birth defects in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) is 2.7%. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with dolutegravir [see Data as follows]. During organogenesis in the rat and rabbit, systemic exposures (AUC) to dolutegravir were less than (rabbits) and approximately 27 times (rats) the exposure in humans at the maximum recommended human dose (MRHD). In the rat pre/post- natal developmental study, maternal systemic exposure (AUC) to dolutegravir was approximately 27 times the exposure in humans at the MRHD.
Data: Animal Data: Dolutegravir was administered orally at up to 1,000 mg per kg daily to pregnant rats and rabbits on gestation Days 6 to 17 and 6 to 18, respectively, and also to rats on gestation day 6 to lactation/post- partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/post-natal (rats) development were observed at up to the highest dose tested. During organogenesis systemic exposures (AUC) to dolutegravir in rabbits were less than the exposure in humans at the maximum recommended human dose (MRHD) and in rats were approximately 27 times the exposure in humans at the MRHD. In the rat pre/post-natal development study, decreased body weight of the developing offspring was observed during lactation at a maternally toxic dose (approximately 27 times human exposure at the MRHD).
Lactation: Risk Summary: The Centers for Disease Control and Prevention recommend that HIV-1-infected mothers in the United States not breastfeed their infants to avoid risking postnatal transmission of HIV-1 infection. It is not known whether dolutegravir is present in human breast milk, affects human milk production, or has effects on the breastfed infant. When administered to lactating rats, dolutegravir was present in milk [see Data as follows]. Because of the potential for (1) HIV-1 transmission (in HIV-negative infants), and (2) developing viral resistance (in HIV-positive infants), instruct mothers not to breastfeed if they are receiving dolutegravir.
Data: Animal Data: Dolutegravir was the primary drug-related component excreted into the milk of lactating rats following a single oral dose of 50 mg per kg on lactation Day 10, with milk concentrations of up to approximately 1.3 times that of maternal plasma concentrations observed 8 hours post-dose.