Use is not recommended.
-According to some authorities: This drug plus atazanavir should be used during pregnancy only if the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B1
US FDA pregnancy category: Not assigned.

Risk summary: Malformative risk with use of this drug in pregnant women is unlikely.

Comments:
-A pregnancy exposure registry is available.
-The manufacturer product information for atazanavir, darunavir, and other coadministered antiretroviral drugs should be consulted.
-This drug interacts with certain oral contraceptives.
-According to some authorities: Viral load should be closely monitored during pregnancy.

Animal studies have failed to reveal evidence of fetal harm at exposures up to 1.4 (rats) and 3.3 (rabbits) times the maximal recommended human dose of 150 mg. There are no controlled data in human pregnancy; however, available data showed no difference in rate of overall birth defects for this drug compared with the background rate in the US reference population.

Placental transfer to the fetus has been reported as low (cord blood/maternal delivery plasma drug ratio less than 0.3).

Exposures to this drug and darunavir were considerably lower during the second and third trimesters of pregnancy compared to postpartum. Low darunavir exposure may be associated with increased risk of treatment failure and increased risk of HIV-1 transmission to the child. This drug plus darunavir should not be started during pregnancy and patients who become pregnant during therapy with this drug plus darunavir should be switched to an alternative regimen.

In 1 study, 6 pregnant subjects were using cobicistat-darunavir (fixed-dose combination) with a background regimen before enrollment; study period included the second and third trimesters, and through 12 weeks postpartum. Of the 6 subjects, 1 had virologic failure with HIV-1 RNA greater than 1000 copies/mL from the third trimester visit through the postpartum period; 5 subjects had sustained virologic response (HIV-1 RNA less than 50 copies/mL) throughout the study period. No clinical data available on the virologic response when cobicistat-darunavir was started during pregnancy.

There are limited data from the use of this drug and atazanavir in pregnant women. Considerably lower exposures of this drug have been reported during pregnancy compared to postpartum; consequently, plasma levels of atazanavir may decrease considerably during pregnancy.

To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com

The APR has received prospective reports of over 350 exposures to cobicistat-containing regimens (over 290 exposed in the first trimester; over 60 exposed in the second/third trimester) resulting in live births; there was no difference between this drug and overall birth defects compared with the background birth defect rate of 2.7% in the US reference population. Enough first-trimester exposures have been monitored to detect at least a 2-fold increased risk of overall birth defects; no such increases detected. The APR has not received enough reports of pregnancies with earliest exposure in the second/third trimester to estimate the birth defect rate. The prevalence of birth defects with first trimester exposures was 3%.

AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

See references

Breastfeeding is not recommended during use of this drug.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected.

See references