Pregnancy: There are no adequate and well-controlled studies in pregnant women. Existing post-marketing data suggest that tolerability and safety of ISENTRESS 400 mg twice daily in pregnant women is consistent with that observed in other populations.
Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant patients exposed to ISENTRESS, an International Antiretroviral Pregnancy Registry has been established.
Antiretroviral Pregnancy Registry (APR) Data: Based on prospective reports from the APR of over 500 exposures to raltegravir during pregnancy resulting in live births (including over 250 exposures in the first trimester), there was no difference between the overall risk of birth defects for raltegravir compared with the background birth defect rate of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP).
The use of ISENTRESS 400 mg twice daily may be considered during pregnancy, if clinically needed. Existing post-marketing data suggest that tolerability and safety of ISENTRESS 400 mg twice daily in pregnant women is consistent with that observed in other populations.
There are no data on the use of ISENTRESS 1200 mg (2 x 600 mg) once daily in pregnant women.
Preclinical studies: Developmental toxicity studies were performed in rabbits (at doses up to 1000 mg/kg/day) and rats (at doses up to 600 mg/kg/day). The highest doses in these studies produced systemic exposures in these species approximately 3- to 4-fold above the exposure at the recommended human dose. No treatment-related external, visceral, or skeletal changes were observed in rabbits. Treatment-related increases over controls in the incidence of supernumerary ribs were seen in rats at 600 mg/kg/day (exposures 4.4-fold above the exposure at the recommended human dose). In both rabbits and rats, no treatment-related effects on embryonic/fetal survival or fetal weights were observed.
In rats, at a maternal dose of 600 mg/kg/day, mean drug concentrations in fetal plasma were approximately 1.5- to 2.5-fold greater than in maternal plasma at 1 hour and 24 hours postdose, respectively. In rabbits, at a maternal dose of 1000 mg/kg/day, mean drug concentrations in fetal plasma were approximately 2% of the mean maternal concentration at both 1 and 24 hours postdose. Toxicokinetic studies demonstrated placental transfer of drug in both species.
Nursing Mothers: It is not known whether raltegravir is secreted in human milk. However, raltegravir is secreted in the milk of lactating rats. In rats, at a maternal dose of 600 mg/kg/day, mean drug concentrations in milk were approximately 3-fold greater than in maternal plasma. Breastfeeding is not recommended while taking ISENTRESS. In addition, it is recommended that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.