Animal studies have failed to reveal evidence of fetal harm. There are no controlled data in human pregnancy; prospective pregnancy data from clinical trials and the pregnancy registry are not enough to adequately assess risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In a study of 15 pregnant women during the second and third trimesters of pregnancy and postpartum, this drug (200 mg twice a day) was evaluated in combination with other antiretroviral agents; 13 women completed the trial through postpartum period (6 to 12 weeks after delivery). Exposure to total drug was generally higher during pregnancy compared with postpartum; difference was less pronounced for unbound drug exposure. Among the women who were virologically suppressed (HIV-1 RNA less than 50 copies/mL) at baseline (9/13), virologic suppression was sustained through the third trimester and postpartum period. Among the women with HIV-1 RNA greater than 50 and less than 400 copies/mL at baseline (3/13), viral loads stayed less than 400 copies/mL. In 1 woman with HIV-1 RNA greater than 1000 copies/mL at baseline, HIV-1 RNA stayed greater than 1000 copies/mL during the study. In this study, 13 infants were born to 13 HIV-infected pregnant women; HIV-1 test results were negative for 11 infants at delivery and were not available for 2 infants.

Placental transfer to the fetus has been reported as variable, usually as moderate to high (cord blood/maternal delivery plasma drug ratio at least 0.3). In 19 mother-infant pairs, the ratio of drug levels in cord blood-to-maternal plasma at delivery ranged from 0.19 to 4.25.

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 100 exposures to regimens containing this drug (over 65 exposed in the first trimester; over 35 exposed in the second/third trimester) resulting in live births; available data showed 1 birth defect among cases of first trimester exposures. Too few exposures to this drug have been monitored to accurately calculate prevalence of birth defects in exposed cases.

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.

This drug 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: Insufficient data available on use of this drug in pregnant women to adequately assess drug-related risk.

Comments:
-A pregnancy exposure registry is available.

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: Yes

Comments:
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing side effects similar to those in adults
-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.

This drug is excreted in breast milk in levels exceeding maternal plasma HIV inhibitory level.

This drug (dose not provided; presumed 200 mg twice a day) was added to the existing antiretroviral regimens of 9 HIV-infected women between days 1 and 14 postpartum. Breast milk and maternal serum samples were collected at 0, 2, 5, 8, and 24 hours after dosing on days 5 and 14 postpartum. Breast milk drug level was 241 mcg/L (range: 161 to 891 mcg/L) on day 5 and 798 mcg/L (range: 161 to 2714 mcg/L) on day 14; milk to plasma ratio was 1.09 and 3.27 on days 5 and 14, respectively.

See references