Coadministration has not been studied. Carvedilol is glucuronidated by UGTs 1A1, 2B4 and 2B7 with additional metabolism by CYP2D6 (and to a lesser extent CYPs 2C9 and 1A2), none of which is affected by sofosbuvir/velpatasvir. However, carvedilol is substrate of P-gp and concentrations may increase due to mild inhibition of P-gp by velpatasvir. Caution is warranted as carvedilol has a narrow therapeutic index.

Coadministration has not been studied. Carvediol and daclatasvir are substrates and inhibitors of P-gp and concentrations of both drugs may increase. Carvedilol can also commonly cause anaemia. Close monitoring is recommended for increased side effects and toxicities including dizziness, bradycardia and GI disturbances for carvedilol.

Coadministration has not been studied and is not recommended as concentrations of velpatasvir may decrease. If use of a proton pump inhibitor is considered medically necessary, the US Prescribing Information recommends sofosbuvir/velpatasvir to be administered with food and taken 4 hours before omeprazole 20 mg but does not recommend the use of other proton pump inhibitors. The European Summary of Product Characteristics states that sofosbuvir/velpatasvir could be administered with food and taken 4 hours before a proton pump inhibitor at a dose not to exceed that comparable to omeprazole 20 mg.

Coadministration of omeprazole is not recommended. If it is considered medically necessary to coadminister, sofosbuvir/velpatasvir should be administered with food and taken 4 hours before omeprazole 20 mg. Coadministration of sofosbuvir/velpatasvir with food 4 hours before omeprazole (20 mg once daily) decreased sofosbuvir Cmax by 21% but increased AUC by 5%; velpatasvir Cmax and AUC decreased by 33% and 26%.

Coadministration has not been studied. As both carvedilol and sofosbuvir are substrates of P-gp, concentrations of sofosbuvir may be increased. However, increasing sofosbuvir concentrations has been shown not to increase the predominant metabolite GS-331007, therefore no dose change should be required.

Coadministration of omeprazole (40 mg once daily) and daclatasvir (60 mg single dose) had no clinically relevant effect on daclatasvir (AUC, Cmax and Cmin decreased by 16%, 36% and 8%, respectively). No dose adjustment of daclatasvir is required.

Coadministration has not been studied but no clinically relevant interaction is expected with proton pump inhibitors. Rabeprazole is metabolised by CYP2C19 and CYP3A4. Daclatasvir has no effect on CYP2C19 and is only a mild inducer of CYP3A4 so a pharmacokinetic interaction is unlikely at clinically relevant concentrations.A study with omeprazole and daclatasvir showed no dose adjustment of daclatasvir is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mebeverine is metabolised by hydrolysis.