Advice for healthcare professionals:
pharmacokinetic data show low exposure values of darunavir boosted with cobicistat (darunavir/cobicistat) during the second and third trimesters of pregnancy
low darunavir exposure may be associated with an increased risk of treatment failure and an increased risk of mother-to-child transmission of HIV infection
therapy with darunavir/cobicistat should not be initiated during pregnancy
switch women who are pregnant and taking darunavir/cobicistat to an alternative regimen: darunavir/ritonavir may be considered as an alternative
report suspected adverse drug reactions with HIV medicines to the Yellow Card Scheme, including treatment failure that results in harm
Darunavir (Prezista) is an antiretroviral medication used to treat and prevent HIV/AIDS. Cobicistat can be co-administered with darunavir as a booster to increase darunavir levels. Darunavir and cobicistat are available in combination in fixed dose products Rezolsta▼ and Symtuza▼.
Data for lower exposure in pregnancy
New pharmacokinetic data based on 6 women enrolled in a Phase 3b study (TMC114HIV3015) showed lower mean exposure (AUC) levels of darunavir boosted with cobicistat (darunavir/cobicistat) during the second trimester (56% lower) and third trimester (50% lower) of pregnancy, compared with 6–12 weeks postpartum. Mean darunavir Cmin concentrations were around 90% lower during the second and third trimesters of pregnancy than during 6–12 weeks postpartum. Exposure of cobicistat was 63% lower during the second trimester and 49% lower during the third trimesters of pregnancy than during 6–12 weeks postpartum.
Low darunavir exposure may be associated with an increased risk of treatment failure and an increased risk of HIV-1 transmission to the child. Mother-to-child transmission did not occur in any of the 6 infants born to the 6 mothers who delivered during study and completed the study. So far, the advice is precautionary, and we are not aware of any clinical pattern to suggest that patient safety has been affected.
Updates to product information
The product information for Prezista (darunavir), Rezolsta▼ (darunavir and cobicistat) and Symtuza▼ (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) will be updated to recommend against use of darunavir/cobicistat in pregnancy. A letter has been sent to relevant healthcare professionals to inform them of this information.
Report suspected adverse drug reactions with HIV medicines
Report any suspected adverse drug reactions with black triangle drugs such as Rezolsta▼ and Symtuza▼ on a Yellow Card. Any cases of material-to-child transmission of HIV due to low treatment efficacy should be reported on a Yellow Card.
Article citation: Drug Safety Update volume 11, issue 12; July 2018: 1.