Reduction in warfarin effect associated with sofosbuvir–velpatasvir

It is a certainty that some patients taking warfarin will be prescribed new direct-acting antiviral agents (DAAs) for hepatitis C, given the increasing use of these medications. This raises the possibility of a drug interaction with warfarin, which heretofore has been rarely described, especially with the new agent sofosbuvir–velpatasvir. This product is highly effective for all genotypes of hepatitis C and is an attractive alternative to other DAAs, especially for more resistant strains. To date, there are no citations on PubMed or in the company literature describing a warfarin interaction with this product, although reports of warfarin antagonism are emerging with other DAAs.1–3 We describe an apparent interaction between warfarin and sofosbuvir–velpatasvir that resulted in a subtarget International Normalized Ratio (INR) and subsequent thrombosis and hospitalization. A 63-year-old man appeared in our emergency department (ED) with leg pain and a cold foot. He had a history of femoral-popliteal bypass surgery and was receiving warfarin to prevent graft thrombosis. His target INR was 2.5–3.5, and he was followed in the facility’s anticoagulation clinic. Fourteen days before arriving at the ED, he had begun treatment for hepatitis C genotype 3a infection with a fixed combination of sofosbuvir 400 mg and velpatasvir 100 mg (1 tablet daily). For the 6 weeks before that, his INR had generally been within the target range while he received a stable total weekly warfarin sodium dose of 102.5 mg (see figure).