Tenofovir use while Breastfeeding
Drugs containing Tenofovir: Truvada, Atripla, Stribild, Viread, Complera, AccessPak for HIV PEP Basic, AccessPak for HIV PEP Expanded with Viracept, AccessPak for HIV PEP Expanded with Kaletra
Tenofovir Levels and Effects while Breastfeeding
Summary of Use during Lactation
Published experience with tenofovir during breastfeeding in HIV-positive mothers and HIV-negative mothers treated for HIV prophylaxis or hepatitis B infection indicates that the exposure of the infant to the drug is trivial. A few infants have been breastfed during maternal tenofovir therapy and no adverse effects have been seen. An expert review of available data concluded that there is currently no justification for contraindicating the use of tenofovir for hepatitis B during breastfeeding. No differences exist in infection rates between breastfed and formula-fed infants born to hepatitis B-infected women, as long as the infant receives hepatitis B immune globulin and hepatitis B vaccine at birth. Mothers with hepatitis B are encouraged to breastfeed their infants after their infants receive these preventative measures. Maternal use of prophylactic vaginal tenofovir (investigational in the U.S.) does not appear to present a great risk to the breastfed infant. In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through at least 12 months of life up to 24 months of life. The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.
Tenofovir has very poor bioavailability and is available commercially as the more bioavailable tenofovir disoproxil fumarate which is metabolized intracellularly to the active metabolite tenofovir diphosphate. The bioavailabilities of tenofovir and tenofovir diphosphate from breastmilk are not known, but presumed to be very low. Maternal Levels. Five exclusively breastfeeding mothers received oral tenofovir 300 mg plus emtricitabine 200 mg and nevirapine 200 mg at the start of labor, then oral tenofovir 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.
In a multicenter study in Malawi and Brazil, mothers were given a single dose of either 600 mg or 900 mg of tenofovir 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.
Women in Malawi received the option B+ regimen for prevention of mother-to-child transmission of HIV consisting of tenofovir, lamivudine and efavirenz between 6 and 8 pm daily. The tenofovir dose was not stated, but was presumably 300 mg daily. Milk samples collected in the morning from 33 women at month 1 postpartum had a median tenofovir concentration of 5 mcg/L (IQR 0 to 6.1 mcg/L). Milk samples collected in the morning from 47 women at month 12 postpartum had a median tenofovir concentration of 2.5 mcg/L (IQR 0 to 5.5 mcg/L).
Seventeen women received 40 mg vaginal doses of 1% tenofovir gel daily for 6 days, with the first and last doses applied in clinic under observation. Two women reported using four doses at home, eleven women reported five doses, and two reported six doses. Breastmilk samples were collected before and 2, 4, and 6 hours after the first and last doses. Only 25% of milk samples contained detectable (>1 mcg/L) tenofovir post-dose on day 0, 12.5% at pre-dose on day 6, and 37.5% post-dose on day 6. Breastmilk tenofovir concentrations ranged from 0 to 0.75 mcg/L on day 0 and from 0 to 1.6 mcg/L on day 6.
Fifty HIV-negative women who were nursing their infants 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. On days 7 and 10 of therapy, peak milk samples were obtained 1 to 2 hours after a dose and trough samples were obtained 23 to 24 hours after the previous dose. The median peak milk tenofovir concentration was 3.2 mcg/L and the trough concentration was 3.3 mcg/L. These values represent an estimated daily dosage of 0.47 to 0.49 mcg/kg, which is less than 0.01% of the proposed infant therapeutic dosage.
Forty-eight HIV+ mothers from Uganda and Nigeria were taking tenofovir, emtricitabine and lamivudine and exclusively nursing their infants. The dosage of tenofovir was not stated, but presumably 300 mg daily. Tenofovir had an average peak concentration of 7.3 mcg/L in breastmilk at 4 hours after the dose. Infant Levels. Five infants were exclusively breastfed by 4 mothers who took tenofovir 245 mg (presumably 300 mg of tenofovir disoproxil fumarate) daily. At an average of 1.8 months of age, infant serum tenofovir concentrations were measured. Tenofovir was undetectable (<0.005 mg/L) in the serum of 4 of the infants, and 0.0055 mg/L in the serum of one infant.
Blood samples were taken from 25 breastfed infants of mothers who were receiving option B+ regimen for prevention of mother-to-child transmission of HIV consisting of tenofovir, lamivudine and efavirenz between 6 and 8 pm daily. The tenofovir dose was not stated, but was presumably 300 mg daily. The median morning infant plasma concentration of tenofovir at 6 months of age was 24 mcg/L (IQR 0 to 51.6 mcg/L). The median morning infant plasma concentration of tenofovir at 12 months of age was 0 mcg/L.
Seventeen women received 40 mg vaginal doses of 1% tenofovir gel daily for 6 days, with the first and last doses applied in clinic under observation. Two women reported four doses at home, eleven women reported inserting five doses, and two reported six doses. Infant blood was collected 6 hours after the maternal dose, which ranged from 1 to 4 hours after breastfeeding. Six infants (37.5%) had detectable tenofovir levels after the maternal dose on day 0, and 12 (75%) of infants post-dose on day 6. In infants with detectable tenofovir serum concentrations, day 6 levels were higher (median 2.4 mcg/L) than on day 0 concentrations (median 0). No difference was seen in the anti-HIV activity of breastmilk between day 0 and day 6.
Fifty HIV-negative women who were nursing their infants 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. A single infant blood sample was obtained after the mother's 7th dose. Of 49 infant blood samples collected, 46 had an undetectable (<0.31 mcg/L) concentration of tenofovir. The 3 with detectable levels contained 0.9, 0.9 and 17.4 mcg/L of tenofovir.
Forty-eight HIV+ mothers from Uganda and Nigeria were taking tenofovir, emtricitabine and lamivudine and exclusively nursing their infants. The dosage of tenofovir was not stated, but presumably 300 mg daily of tenofovir disoproxil fumarate. Their infants had an average age of 100 days. No infant had measurable tenofovir in plasma.
Effects in Breastfed Infants
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.
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.
Fourteen mothers were treated with tenofovir (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.
In a study of 17 nursing mothers who receive 40 mg of 1% vaginal tenofovir daily for 6 days, 4 of 17 infants had one or more adverse effects. There were a total of 8 adverse reactions. Seven were mild, and one had diarrhea that was thought to be related to tenofovir exposure.
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.
A study of 136 breastfed infants of mothers who took tenofovir, 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.
Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
Alternate Drugs to Consider
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