Darunavir/cobicistat — marketed as Prezcobix (Janssen) in the United States — should not be given to pregnant women with HIV because of substantially lower exposures of the two medications during pregnancy, the FDA said.
The agency updated the label for the once-daily, fixed-dose tablet to reflect the change, which it said was based on data from a small clinical trial involving pregnant women.
The FDA said darunavir/cobicistat should not be initiated in pregnant women. In women who become pregnant while using it, an alternative regimen is recommended.
“The FDA has no definitive answer for why the levels are so low, but it is consistent with other cobicistat-boosted regimens,” FDA spokesman Jeremy Kahn told Infectious Disease News.
Darunavir/cobicistat was approved by the FDA in 2015 to treat of HIV-1 infection in adults. It was evaluated in combination with a background regimen in seven pregnant women who started darunavir/cobicistat before enrolling and were willing to remain on it for the remainder of the study. They were followed through the second and third trimesters and 12 weeks of postpartum. Six women completed the study.
According to the FDA, exposure to darunavir and cobicistat “was substantially lower during the second and third trimesters of pregnancy compared with postpartum.” A sustained virologic response — HIV-1 RNA less than 50 copies/mL — was recorded throughout the study period in five women. However, one woman experienced virologic failure, with HIV-1 RNA above 1,000 copies/mL from the third trimester until the postpartum period, the agency reported.
“Cobicistat (the pharmacokinetic booster) exposures are low in the third trimester of pregnancy, and thus the drugs that get boosted also have decreased exposures,” Kahn said. “The reason is likely multifactorial but could be due to increased volume of distribution or increased metabolism of the drug or a combination of intrinsic factors. There are no plans to study this further as the results will not change. Instead, the focus should be on other antiretroviral drug regimens in pregnancy.”
The FDA said there are no clinical data regarding the virologic response when darunavir/cobicistat is initiated during pregnancy. It said there were no new clinically relevant safety findings compared with the known safety profile of darunavir/cobicistat in adults with HIV-1. – by Marley Ghizzone
FDA. Prezcobix pregnancy label updates. http://s2027422842.t.en25.com/e/es?s=2027422842&e=96974&elqTrackId=B1F0B909CCF90C71B9C490C37BFE6647&elq=0600127116964d22a78ccf5971c6f8a0&elqaid=3795&elqat=1. Accessed June 6, 2018.
Disclosures: Kahn works for the FDA.