This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B2
US FDA pregnancy category: B

Animal studies have failed to reveal evidence of embryolethality or fetotoxicity. Placental transfer to the fetus has been reported as minimal to low (cord to maternal plasma ratio about 0.14). There are no controlled data in human pregnancy.

Due to its lower rate of viral suppression, this drug is not recommended as part of initial combination therapy for antiretroviral-naive pregnant women.

Compared with nonpregnant patients, plasma drug levels were reduced in pregnant women, especially during the third trimester. Although 1250 mg orally twice a day yields sufficient drug levels in pregnant women, 750 mg orally 3 times a day shows more variable and low drug levels.

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

According to the APR, there is a modest but statistically significant increase in overall birth defect rates when compared with the Metropolitan Atlanta Congenital Defects Program (MACDP); the prevalence of birth defects was 3.9% among cases of first-trimester exposures reported, compared with 2.76% for MACDP rate. No pattern of birth defects has been detected; the clinical relevance of this statistical finding is unclear. Enough first-trimester exposures to this drug have been monitored to detect at least a 1.5-fold increase in risk of overall birth defects and a 2-fold increase in risk of birth defects in the cardiovascular and genitourinary systems; no such increase in birth defects has been observed with this drug.

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 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

At 6, 12, and 24 weeks postpartum, 26 samples of breast milk and maternal serum were collected from mothers using this drug (dose not provided) as part of combination antiretroviral therapy (cART). At about 14, 14, and 16 hours after the last dose, breast milk drug levels averaged 49 mcg/L at 6 weeks postpartum (10 samples), 51 mcg/L at 12 weeks postpartum (7 samples), and 184 mcg/L at 24 weeks postpartum (9 samples), respectively; milk levels averaged 8% (interquartile range: 4% to 14%) of maternal plasma levels. Serum drug levels in their infants at 6, 12, and 24 weeks of age were undetectable by high performance liquid chromatography mass spectrometry analysis; timing of infant plasma sampling was not specified. In a related study (same authors), milk to plasma ratio of this drug was 0.21 in 29 patients.

In 26 breastfeeding mothers using 1250 mg orally twice a day (plus zidovudine and lamivudine) for HIV infection, blood and breast milk samples were collected at delivery, and at 2, 6, 14, and 24 weeks postpartum at various times after the previous nelfinavir dose; blood samples from their infants were collected at various times between 2 and 24 weeks postpartum. The 104 breast milk samples were analyzed for parent drug and its active metabolite, hydroxy-t-butylamidenelfinavir (M8). Breast milk levels of parent drug averaged 83 mcg/L at birth, 358 mcg/L at 2 weeks, 286 mcg/L at 6 weeks, 233 mcg/L at 14 weeks, and 180 mcg/L at 24 weeks postpartum; the M8 metabolite was undetectable (less than 10 mcg/L) in most samples, with 32 mcg/L as the highest levels observed at any time. Breast milk levels of the parent drug usually declined during the dosing interval; M8 levels were relatively stable. The levels of parent drug and M8 were undetectable (less than 10 mcg/L) in 20 of 28 infant blood samples; the highest levels detected were 30 and 32 mcg/L for the parent drug and M8, respectively. Overall, amount of drug in breast milk was low and resulted in non-significant drug exposure in breastfed infants through 24 weeks of age.

During the first 5 days of therapy, postpartum milk was collected just before and 2 hours after dosing in 5 women using 1250 mg orally twice a day (as part of highly-active cART). Breast milk drug levels were ranged 6% to 24% of maternal serum level; the M8 metabolite was not detectable in milk. Additional data regarding timing or actual breast milk levels were not specified.

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.
-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