Coadministration with levonorgestrel as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel for HRT is coformulated with estradiol in a transdermal patch. Transdermally applied estrogens and progestogens are less susceptible than oral hormones to drug interactions by enzyme inducers/inhibitors due to avoidance of first-pass metabolism in the liver. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Estradiol is metabolized by CYPs 3A4 and 1A2, and is glucuronidated. None of these pathways is affected by sofosbuvir/velpatasvir. However, velpatasvir is an inhibitor of OATP and in vitro studies have shown estradiol to be a high-affinity OATP substrate: the clinical significance of this is unknown. An OATP-mediated interaction is possible, which may increase exposure of estradiol to a limited extent. This is unlikely to be clinically relevant with short durations of treatment for hepatitis C.