Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4 and CYP1A2 and is glucuronidated. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). These pathways are not 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.