FDA approved updates to the PREZCOBIX (darunavir and cobicistat) label to state PREZCOBIX is not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy. Listed below are the specific changes to the label.
Section 2: DOSING AND ADMINISTRATION
2.5 Not Recommended During Pregnancy
PREZCOBIX is not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy
PREZCOBIX should not be initiated in pregnant women. An alternative regimen is recommended for women who become pregnant during therapy with PREZCOBIX.
Section 8: USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Clinical Considerations
Not Recommended During Pregnancy
PREZCOBIX is not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy.
PREZCOBIX should not be initiated in pregnant women. An alternative regimen is recommended for women who become pregnant during therapy with PREZCOBIX.
Data
Human Data
Darunavir/Cobicistat: PREZCOBIX in combination with a background regimen was evaluated in a clinical trial of 7 pregnant women taking PREZCOBIX prior to enrollment and who were willing to remain on PREZCOBIX throughout the study. The study period included the second and third trimesters, and through 12 weeks postpartum. Six women completed the trial.
Exposure to darunavir and cobicistat as part of an antiretroviral regimen was substantially lower during the second and third trimesters of pregnancy compared with postpartum.
One out of 6 women who completed the study experienced virologic failure with HIV-1 RNA >1,000 copies/mL from the third trimester visit through the postpartum period. Five women had sustained virologic response (HIV RNA < 50 copies/mL) throughout the study period.There are no clinical data on the virologic response when PREZCOBIX is initiated during pregnancy.
There were no new clinically relevant safety findings compared with the known safety profile of PREZCOBIX in HIV-1-infected adults.
Section 12: Clinical Pharmacology was updated to provide the pharmacokinetic results of total darunavir exposures during the second and third trimester of pregnancy and postpartum.
In summary, in the second trimester of pregnancy, total darunavir AUC24h, and Cmin were 56%, and 92% lower, respectively, compared to postpartum. In the third trimester of pregnancy, total DRV AUC24h, and Cmin values were 50%, and 89% lower, respectively, compared to postpartum.
Additionally, in the second trimester of pregnancy, cobicistat AUC24h, and Cmin were 63%, and 83% lower, respectively, compared to postpartum. In the third trimester of pregnancy, cobicistat, AUC24h, and Cmin values were 49%, and 83% lower, respectively, compared to postpartum.
Section 2: DOSING AND ADMINISTRATION
2.5 Not Recommended During Pregnancy
PREZCOBIX is not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy
PREZCOBIX should not be initiated in pregnant women. An alternative regimen is recommended for women who become pregnant during therapy with PREZCOBIX.
Section 8: USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Clinical Considerations
Not Recommended During Pregnancy
PREZCOBIX is not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy.
PREZCOBIX should not be initiated in pregnant women. An alternative regimen is recommended for women who become pregnant during therapy with PREZCOBIX.
Data
Human Data
Darunavir/Cobicistat: PREZCOBIX in combination with a background regimen was evaluated in a clinical trial of 7 pregnant women taking PREZCOBIX prior to enrollment and who were willing to remain on PREZCOBIX throughout the study. The study period included the second and third trimesters, and through 12 weeks postpartum. Six women completed the trial.
Exposure to darunavir and cobicistat as part of an antiretroviral regimen was substantially lower during the second and third trimesters of pregnancy compared with postpartum.
One out of 6 women who completed the study experienced virologic failure with HIV-1 RNA >1,000 copies/mL from the third trimester visit through the postpartum period. Five women had sustained virologic response (HIV RNA < 50 copies/mL) throughout the study period.There are no clinical data on the virologic response when PREZCOBIX is initiated during pregnancy.
There were no new clinically relevant safety findings compared with the known safety profile of PREZCOBIX in HIV-1-infected adults.
Section 12: Clinical Pharmacology was updated to provide the pharmacokinetic results of total darunavir exposures during the second and third trimester of pregnancy and postpartum.
In summary, in the second trimester of pregnancy, total darunavir AUC24h, and Cmin were 56%, and 92% lower, respectively, compared to postpartum. In the third trimester of pregnancy, total DRV AUC24h, and Cmin values were 50%, and 89% lower, respectively, compared to postpartum.
Additionally, in the second trimester of pregnancy, cobicistat AUC24h, and Cmin were 63%, and 83% lower, respectively, compared to postpartum. In the third trimester of pregnancy, cobicistat, AUC24h, and Cmin values were 49%, and 83% lower, respectively, compared to postpartum.
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
Elizabeth Thompson
Division of Antiviral Products
Food and Drug Administration
Michael Stanfield Jr.
Division of Antiviral Products
Food and Drug Administration
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