Tenofovir alafenamide safe to use in breastfeeding mothers with CHB

The first human pharmacokinetic study of tenofovir alafenamide (TAF; commercially sold as Vemlidy) monotherapy in breastfeeding women with chronic hepatitis B (CHB) has found low concentrations of TAF and tenofovir in the breastmilk, with negligible exposure to infants.

“These results support the use of TAF to prevent mother to child transmission (MTCT) in pregnant and breastfeeding women [with CHB],” the researchers said.

The study was presented by Tahrima Kayes from Liverpool Hospital, Australia, at The Liver Meeting 2021 by the American Association for the Study of Liver Diseases (AASLD 2021).

Kayes and colleagues performed a phase IV, open-label, single-arm, multicentre study to assess the pharmacokinetics of TAF and tenofovir in breastfeeding women with CHB, particularly those requiring antiviral therapy during their third trimester for the prevention of MTCT or any alternative indication. Mothers were obliged to breastfeed for the most part (small amounts of formula were allowed).

TAF 25 mg daily was administered during the third trimester of pregnancy or postpartum. The researchers collected samples within 6 months postpartum and after being on TAF for a minimum of 4 weeks. They obtained maternal blood (n=10), breastmilk (n=10), and infant urine samples (n=7) following an observed dose for each woman.

Liquid chromatography-mass spectrometry analyses using validated methods (lower limit of quantification tenofovir 1.00 ng/mL for blood/breastmilk and 10.0 ng/mL for urine; TAF 0.05 ng/mL for blood/breast milk) were carried out to measure drug concentrations. Noncompartmental analyses were also conducted to quantify area under the curve (AUC), half-life, C_max and T_max.

The researchers recruited 10 women across three centres and found low maternal TAF concentration in plasma (9 ng/mL; range, 0.6–70) and breastmilk (0.6 ng/mL; range, 0.2–1.4). In addition, maternal tenofovir concentration in plasma was 13 ng/mL (range, 9–14) and breastmilk 31 ng/mL (range, 19–44). [AASLD 2021, abstract 772]

Tenofovir AUC was lower by 34.4 percent in plasma than breastmilk, while TAF AUC was lower by 2.0 percent in breastmilk than plasma. TAF had a half-life of 0.94 and 0.81 in plasma and breastmilk, respectively, while tenofovir concentration remained steady over 24 hours.

After ingestion, plasma T_max for TAF was 0.5 hours with undetectable concentrations at 6–8 hours. Of note, there were tenofovir concentrations detected in three of seven infant urine samples at 12, 24, and 25 ng/mL, respectively.

“In newborns, average weight in Australia and New Zealand is 3.3–3.4 kg and reported maximal daily breastmilk intake is 152.6 mL/kg/day; thus, newborn consumes 503.6–518.8 mL breastmilk daily with maximum 25.5 mcg tenofovir exposure,” Kayes said. “This is approximately 0.03 percent of the recommended daily dose of tenofovir in children >2 years old.”

MTCT is responsible for >90 percent of people with CHB. The World Health Organization recommends tenofovir disoproxil fumarate (TDF) for the prevention of MTCT when hepatitis B virus DNA is ≥5.3 log10 IU/mL. TAF, or Vemlidy, is a prodrug of tenofovir that is closely related to TDF, with a different pharmacology and enhanced bone and renal safety.