No teratogenic effects were observed in rats or rabbits at maternally toxic doses producing maternal exposures (AUC) 2 times (rats) and comparable to (rabbits) exposure in humans given 400 mg once daily. In the pre- and postnatal development assessment in rats, atazanavir produced transient body weight loss or gain suppression in the offspring at a maternally toxic dose. Offspring were unaffected at a lower dose which produced maternal exposure equivalent to that observed in humans given 400 mg once daily.
In clinical trial AI424-182, Reyataz/ritonavir (300/100 mg or 400/100 mg) in combination with zidovudine/lamivudine was administered to 41 pregnant women during the 2nd or 3rd trimester. Among the 39 women who completed the study, 38 women achieved an HIV RNA <50 copies/mL at time of delivery. Six (6) of 20 (30%) women on Reyataz/ritonavir 300/100 mg and 13 of 21 (62%) women on Reyataz/ritonavir 400/100 mg experienced grades 3-4 hyperbilirubinemia. There were no cases of lactic acidosis observed in the clinical trial AI424-182.
Forty (40) infants had test result that were negative for HIV-1 DNA at the time of delivery and/or during the first 6 months postpartum. All 40 infants received antiretroviral prophylactic treatment containing zidovudine. Three (3) of 20 infants (15%) born to women treated with Reyataz/ritonavir 300/100 mg and 4 of 20 infants (20%) born to women treated with Reyataz/ritonavir 400/100 mg experienced grade 3-4 bilirubin. There was no evidence of pathologic jaundice and 6 of 40 infants in this study received phototherapy for a maximum of 4 days. There were no reported cases of kernicterus in neonates.
No dosage adjustment is required if used during pregnancy.
Reyataz should be used during pregnancy only if the potential benefit justifies the potential risk.
It is not known whether atazanavir is secreted in human milk. A study in lactating rats demonstrated that atazanavir is secreted in milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Reyataz.
Post-Marketing Data: As of December 2009, there were 315 identified cases with prospective 1st trimester exposure to atazanavir and known outcome in the post-marketing database. There was no association between atazanavir and specific birth defects observed in the post-marketing data.
Antiretroviral Pregnancy Registry Data: As of January 2010, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 635 exposures to atazanavir-containing regimens (425 exposed in the 1st trimester and 160 and 50 exposed in 2nd and 3rd trimester, respectively). Birth defects occurred in 9 of 393 (2.3%) live births (1st trimester exposure) and 5 of 212 (2.4%) live births (2nd/3rd trimester exposure). There was no association between atazanavir and specific birth defects observed in the APR.
Labor and Delivery: Hyperbilirubinemia occurred frequently during treatment with Reyataz. It is not known whether Reyataz administered to the mother during pregnancy will exacerbate physiological hyperbilirubinemia and lead to kernicterus in neonates and young infants. In the prepartum period, additional monitoring should be considered.