Animal studies have failed to reveal evidence of adverse developmental outcomes at systemic exposures about 20 times (rats) and 5 times (rabbits) the exposure in humans (at the recommended dosage of 300 mg twice a day); pre-implantation loss occurred in rats exposed to maternotoxic doses. There are no controlled data in human pregnancy.

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

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 inform a 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:
-Minimal information available on the use of this drug during breastfeeding.
-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.

A woman with HIV received 150 mg twice a day (with lamivudine and lopinavir-ritonavir); her infant (who received zidovudine for 14 days at birth) was exclusively breastfed until 6 months of age, then partially breastfed until 7 months of age. At 5 months postpartum, paired maternal milk and plasma samples were collected before a dose and at 1, 2, 4, 6, 8, and 12 hours after a dose. Peak milk level of 415 mcg/L was reached 2 hours after dosing; the level was almost as high at 4 hours, and then fell to less than 100 mcg/L at 12 hours after dosing. Milk level averaged 193 mcg/L, which yields an infant dose of 29 mcg/kg/day; this translates to a weight-adjusted infant dosage of 0.6%, assuming a maternal weight of 60 kg. A single infant plasma sample was collected (time in relation to dose and nursing not provided) at 5.5 months of age during exclusive breastfeeding; this drug was undetectable (less than 2.5 mcg/L) in the infant's plasma. Clinical and laboratory assessment of the infant at 2, 4, and 8 weeks, and 3, 6, 9, and 12 months after birth showed normal development; full blood cell count, renal, and liver parameters remained within normal range, HIV-DNA polymerase chain reaction (PCR) results were consistently negative, and an HIV antibody test was negative at 12 months of age.

See references