Animal studies have failed to reveal evidence of embryotoxicity or teratogenicity; no adverse developmental effects observed at exposures less than 1-fold (mice and rabbits) and 3-fold (rats) human exposures at the recommended clinical dose of this drug boosted with ritonavir. 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 of darunavir/cobicistat are 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. Darunavir/cobicistat should not be started during pregnancy and patients who become pregnant during therapy with darunavir/cobicistat should be switched to an alternative regimen. According to some authorities, darunavir/ritonavir may be considered as an alternative.

In a clinical trial, darunavir/ritonavir (darunavir 600 mg plus ritonavir 100 mg twice a day or darunavir 800 mg plus ritonavir 100 mg once a day) in combination with a background regimen was evaluated in 36 pregnant women during the second and third trimesters and postpartum. Pharmacokinetic data showed exposure to darunavir/ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6 to 12 weeks); exposure reductions during pregnancy were greater with the once-daily regimen than with the twice-daily regimen. Virologic response was preserved throughout the trial with both regimens. No mother-to-child transmission occurred in the 31 infants born to the 31 HIV-infected women who completed the trial through delivery or postpartum. Darunavir/ritonavir was well-tolerated during pregnancy and postpartum.

According to some authorities, the twice-daily regimen (darunavir 600 mg plus ritonavir 100 mg twice a day with food) is recommended in pregnant patients; the once-daily regimen (darunavir 800 mg plus ritonavir 100 mg once a day) should only be considered in certain pregnant patients who are already on a stable darunavir 800 mg plus ritonavir 100 mg once-daily regimen before pregnancy, who are virologically suppressed (HIV-1 RNA less than 50 copies/mL), and if switching to the twice-daily regimen may compromise tolerability/compliance. According to some experts, the once-daily regimen is not recommended in 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 850 exposures to darunavir-containing regimens (over 550 exposed in the first trimester; over 300 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 prevalence of birth defects with first trimester and second/third trimester exposures was 3.4% and 2.6%, respectively.

AU TGA pregnancy category B2: 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 are inadequate or may be lacking, but available data show no 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.

With cobicistat: Use is not recommended.
With ritonavir: This drug should be used during pregnancy only if the benefit outweighs the risk.

AU TGA pregnancy category: B2
US FDA pregnancy category: Not assigned.

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

Comments:
-A pregnancy exposure registry is available.
-According to some experts, this drug must be boosted with low-dose ritonavir (using the twice-daily regimen).
-Females of Reproductive Potential: This drug may reduce efficacy of combined hormonal contraceptives and progestin-only pill; patients should be advised to use an effective alternative (nonhormonal) contraceptive measure or add a barrier method of contraception; due to potential for hyperkalemia, clinical monitoring is recommended if coadministered with drospirenone.

See references

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug may be preferred.

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

Comments:
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing side effects.
-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.
-Local guidelines should be consulted if replacement feeding is not an option.

See references