Coadministration has not been studied and is contraindicated. Concentrations of velpatasvir and sofosbuvir may decrease due to induction of P-gp and/or CYPs 2B6, 2C8 and 3A4 by St John's wort, resulting in loss of efficacy and potential virological failure. However, the constituent of St John’s Wort responsible for induction of enzymes and transporters, hyperforin, can be highly variable between extracts. A recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (< 1 mg/day) of St John’s Wort. Coadministration may be considered with St John’s Wort formulations that clearly state the hyperforin content and which have a total daily hyperforin dose of < 1 mg.