This drug should be used during pregnancy only if clearly needed.

AU TGA pregnancy category: B1
US FDA pregnancy category: B

Comments:
-A pregnancy exposure registry is available.

Animal studies have failed to reveal evidence of embryofetal toxicity, reproductive toxicity, or teratogenicity; incidence of fetal variations and malformations was not increased in mice at exposures about 60-fold higher or in rabbits at about 120-fold higher than human exposures at the recommended daily dose. There are no controlled data in human pregnancy; however, this drug has been evaluated in a limited number of women during pregnancy. Data in pregnant women (between 300 to 1000 outcomes) showed no malformations, fetotoxicity, or neonatal toxicity with this drug.

Placental transfer to the fetus has been reported as high (cord blood/maternal delivery plasma drug ratio greater than 0.6). In studies of pregnant women using this drug, the cord-to-maternal-blood ratio ranged from 0.85 to 1.2.

In a preexposure prophylaxis trial in women without HIV infection, there was no increase in congenital anomalies and no overall difference in rate of pregnancy loss in the arm containing this drug. In a US cohort study, exposure to this drug was not associated with an increase in specific/overall birth defect risk; after adjusting for birth cohort and other factors, maternal use of this drug resulted in no increase in possibility of adverse metabolic, growth/development, cardiac, neurological, or neurodevelopmental outcomes.

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 3700 exposures to emtricitabine-containing regimens (over 2600 exposed in the first trimester; over 1100 exposed in the second/third trimester) resulting in live births. Enough first trimester exposures have been monitored to detect at least a 1.5-fold increased risk of overall birth defects and a 2-fold increase in cardiovascular and genitourinary defects (the more common classes); no such increases detected. The prevalence of birth defects with first trimester and second/third trimester exposures was 2.3% and 2.1%, respectively. Among pregnant women in the US reference population, the background birth defect rate is 2.7%.

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 B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

See references

Samples of breast milk obtained from 5 HIV-1-infected women show that this drug is secreted in human milk. Average peak and trough drug levels in breast milk were 679 and 177 mcg/L, respectively. According to author estimation, an exclusively breastfed infant would receive about 2% of the proposed dose for infants and achieve serum levels that may lead to emergence of viral resistance to this drug. Breastfeeding infants whose mothers are being treated with emtricitabine may be at risk for developing viral resistance to the drug; other drug-related risks in such infants are unknown.

Preexposure prophylaxis, using this drug (200 mg/day) and tenofovir disoproxil fumarate, was administered by directly observed therapy for 10 days to 50 women without HIV infection who were breastfeeding their infants. On days 7 and 10 of therapy, peak and trough milk samples were collected 1 to 2 hours after dosing and 23 to 24 hours after the previous dose, respectively; a single infant blood sample was collected after the mother's 7th dose. Median peak and trough milk emtricitabine levels were 212.5 and 183 mcg/L, respectively; these levels correspond to a daily dose of 27.5 to 31.5 mcg/kg (estimated), which is about 0.5% of the proposed therapeutic dose for infants. Of 49 infant blood samples collected, 47 had detectable emtricitabine levels (median plasma level: 13.2 mcg/L); plasma levels were 16.6 mcg/L in infants younger than 13 weeks and 10.5 mcg/L in infants at least 13 weeks of age. Diarrhea lasting 2 to 3 days was reported in 2 of the 50 breastfed infants; no other side effects were reported.

HIV-infected mothers (n=48) from Uganda and Nigeria were using this drug (dose not provided; presumed 200 mg/day), tenofovir, and lamivudine and exclusively breastfeeding their infants. Median peak drug level in breast milk was 933 mcg/L at 5.1 hours after dosing. This drug was detectable in 19% of their infants (median level: 18.5 ng/mL); average infant age was 100 days.

During ongoing therapy, this drug was measured after a 300-mg dose to 6 nursing mothers with HIV infection. Median peak breast milk level was 872 mcg/L (range: 696 to 1063 mcg/L) at 3 hours; 1 breastfed infant had detectable drug serum level of 17.5 mcg/L.

Breastfeeding is not recommended during use of this drug. If replacement feeding is not an option, the WHO recommends a triple-drug regimen for HIV-infected women who are nursing; this drug is included in the first-choice regimen.

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.

See references