Is Tenofovir Disoproxil Fumarate safe while breastfeeding?

Effects on the breastfed infant

Two newborn infants whose mothers were treated with tenofovir 245 mg (presumably 300 mg of tenofovir disoproxil fumarate) daily were exclusively breastfed for 3 months. At 4 months of age, neither showed any adverse outcomes on standard developmental parameters.[ 24 ] Five women with hepatitis B infection were treated with tenofovir disoproxil fumarate 300 mg daily beginning in the third trimester of pregnancy and continuing postpartum. Although instructed not to breastfeed, 5 mothers breastfed (extent not stated) their newborn infants. No short-term adverse reactions were seen and the infants HBsAg was negative between 28 and 36 weeks of age.[ 26 ] Fourteen mothers were treated with tenofovir disoproxil fumarate (dosage unspecified) during pregnancy (12 beginning in the first trimester) for hepatitis B. Three of the mothers breastfed while taking tenofovir. No adverse outcomes were noted in their breastfed infants up to 1 year of age.[ 27 ] In a study of 50 infants breastfed by HIV-negative women who were given pre-exposure prophylaxis daily with the combination of tenofovir disoproxil fumarate 300 mg and emtricitabine 200 mg by directly observed therapy for 10 days, 2 infants reportedly had diarrhea lasting 2 to 3 days. No other side effects were reported.[ 15 ] A study of 136 breastfed infants of mothers who took tenofovir disoproxil fumarate, efavirenz and lamivudine during pregnancy and postpartum (Option B+) in Malawi measured bone markers at 1, 6 and 12 months of age. Markers included bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen. Although tenofovir is known to affect bone density and bone mineral density in adults, no effects were seen on infants bone markers in the study.[ 28 ] In a long-term study of tenofovir disoproxil fumarate for chronic hepatitis B, 3 women reportedly breastfed their infants (extent not stated). None of the infants had any adverse effects up to 1 year of age.[ 29 ] A study of pregnant women with hepa

Effects on milk supply

A preliminary study of Ugandan women compared the milk composition of women receiving a tenofovir-based regimen for HIV to that of women who were not infected with HIV. Women with HIV on tenofovir-based antiretroviral therapy had higher milk calcium in the first months of lactation (193 and 188 mg/L compared to 177 and 172 mg/L at 2 and 14 weeks postpartum, respectively) and a greater overall reduction in the first year of lactation than women without HIV (10 and 23% decrease compared to 8% and 16% decrease at 6 and 12 months). However, the only statistically significant differences were at 14 weeks postpartum for serum calcium and at 6 to 12 months for the percentage decrease in serum calcium in the HIV-infected women.[ 37 ] A study of mothers taking tenofovir disoproxil fumarate during pregnancy for prevention of mother-to-child transmission of hepatitis B compared the breastfeeding rates between mothers who stopped tenofovir at delivery, and at 4 or 12 weeks postpartum, according to maternal desire. The study found no differences in serum ALT values among the groups, but the breastfeeding rates at birth were markedly different. All women received standardized counseling that breastfeeding is permitted during tenofovir therapy and that encouraged breastfeeding. Eighty percent of those who discontinued tenofovir at delivery chose to breastfeed, while only 25% randomized to 4 weeks of tenofovir and 42% randomized to 12 weeks of tenofovir chose to breastfeed.[ 38 ] The fact that the study was neither randomized nor blinded and the dropout rate was rather high undermines the conclusions. An observational study of women treated with tenofovir disoproxil fumarate for hepatitis B during pregnancy compared the breastfeeding rates of three groups of women. All women were given counseling on the safety of tenofovir during breastfeeding. Nevertheless, those who continued tenofovir for 4 or 8 weeks postpartum had much lower rates of breastfeeding, 25% and 42% respectively, th

Levels in milk

Tenofovir has poor bioavailability and is available commercially as the more bioavailable tenofovir disoproxil fumarate. Tenofovir disoproxil fumarate releases tenofovir in the bloodstream. It is metabolized intracellularly to the active metabolite tenofovir diphosphate. The bioavailability of tenofovir and tenofovir diphosphate from breastmilk are not known, but presumed to be extremely low. Maternal Levels. Five exclusively breastfeeding mothers received oral tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg and nevirapine 200 mg at the start of labor, then oral tenofovir disoproxil fumarate 300 mg daily and emtricitabine 200 mg for 7 days postpartum. A total of 16 concurrent maternal blood and milk samples were collected on days 1, 2, 3, and 7 postpartum between 10 minutes and 21 hours after the mothers doses. Median peak and trough tenofovir concentrations in breastmilk were 14.1 mcg/L and 6.8 mcg/L, respectively. The authors estimated that an exclusively breastfed infant would receive about 0.03% of the proposed infant dose for tenofovir and achieve trivial infant serum concentrations that would likely have no adverse consequences.[ 12 ] In a multicenter study in Malawi and Brazil, mothers were given a single dose of either 600 mg or 900 mg of tenofovir disoproxil fumarate during labor. Breastmilk samples were collected from mothers at various times postpartum. Tenofovir was detected ( 2.5 mcg/L) in three-fourths of samples collected from 25 mothers during the first 2 days postpartum. Levels ranged from 6.3 to 17.8 mcg/L. At 4 to 6 days postpartum, only one milk sample of 21 had a detectable tenofovir level of 15.7 mcg/L.[ 13 ] Women in Malawi received the option B+ regimen for prevention of mother-to-child transmission of HIV consisting of tenofovir disoproxil fumarate, lamivudine and efavirenz between 6 and 8 pm daily. The tenofovir disoproxil fumarate dose was not stated, but was presumably 300 mg daily. Milk samples collected in the morning fro

Alternatives LactMed lists

• Lamivudine