Coadministration with sofosbuvir/velpatasvir has not been studied. Coadministration of rosuvastatin (10 mg single dose) and velpatasvir (100 mg once daily) alone increased rosuvastatin Cmax and AUC by 160% and 170%. The effect on velpatasvir exposure was not studied but no change is expected. No effect on sofosbuvir is expected. Rosuvastatin may be administered with sofosbuvir/velpatasvir at a dose that does not exceed 10 mg. Note, rosuvastatin is contraindicated in patients with active liver disease and should be used with caution in patients who consume excessive quantities of alcohol and/or have a history of liver disease.

Coadministration of atorvastatin (40 mg, single dose) and sofosbuvir/velpatasvir (400/100 mg, once daily) increased atorvastatin Cmax and AUC by 68% and 54%, respectively. This is likely due to inhibition of P-gp and/or BCRP by velpatasvir. The European SmPC for sofosbuvir/velpatasvir advises that no adjustment of sofosbuvir/velpatasvir or atorvastatin is required, but the US Prescribing Information warns for an increased risk of myopathy, including rhabdomyolysis. The amber call reflects the more cautious option. Consider asking patients to self report potential side effects of increased concentrations such as muscle pain. Based on the study data, dose reductions could be discussed for patients prescribed more than 40 mg as this has not been studied.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites by CYPs 2C19, 3A4, 2B6, and 1A2 which are not affected by sofosbuvir/velpatasvir. [Note, the European SmPC for clopidogrel contraindicates it use in severe hepatic impairment but the US Prescribing Information states no dose alteration.]

Coadministration with sofosbuvir/velpatasvir has not been studied. Based on drug interaction studies conducted with velpatasvir alone, no clinically significant drug interactions have been observed with pravastatin. Coadministration of pravastatin (40 mg single dose) and velpatasvir (100 mg once daily) increased pravastatin Cmax and AUC by 28% and 35% (n=18). No effect on sofosbuvir/velpatasvir is expected.