Plasma and breast milk pharmacokinetics of tenofovir alafenamide in mothers with chronic hepatitis B infection

Abstract

Background: Antenatal antiviral therapy (AVT) is effective in preventing mother-to-child transmission (MTCT) in chronic hepatitis B (CHB); tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There are no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB. Aim: To assess the pharmacokinetics of TAF/TFV in breastfeeding women with CHB on TAF monotherapy. Methods: Pregnant women with CHB requiring AVT commenced TAF 25 mg daily at third trimester or postpartum. Sample collection occurred while breastfeeding and taking TAF for minimum 4 weeks. Maternal blood, breast milk and infant urine samples were collected. Drug concentrations were measured by LCMS/MS analyses using validated methods. Non-compartmental analyses were performed to quantify the pharmacokinetic parameters. Results: Eight women provided samples. In breast milk and plasma, median TAF half-life was 0.81 and 0.94 h, respectively, and Cmax 1.69 and 120.5 ng/ml, respectively. Median maternal breast milk to plasma (M/P) ratio of TAF was 0.029; for and TFV it was 2.809. The relative infant dose of TAF was 0.005% of maternal dose, well below safety threshold of 5–10%. TFV was detectable in three out of seven infant urine samples with median steady-state concentration of 5 ng/ml being 300–2500 times less than reported adult steady-state urine concentrations in those taking TAF and TDF, respectively. Conclusions: In this first pharmacokinetic study of TAF monotherapy in breastfeeding women with CHB, concentrations of TAF and TFV were low in breast milk with negligible infant exposure, supporting the use of TAF to prevent MTCT.