Frequent monitoring of relevant laboratory parameters (e.g., International Normalized Ratio [INR] in patients taking warfarin) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

A case was reported of a 63-year-old man on warfarin (52.5 mg, weekly) who was initiated on ribavirin (600 mg, twice daily) and sofosbuvir (400 mg, once daily) for chronic HCV infection. His other medications were venlafaxine, omeprazole, diazepam, gabapentin, metoprolol tartrate, saw palmetto, ascorbic acid, and paracetamol. During the 12 weeks of his treatment, his dose of warfarin was increased from 52.5 to 77.5 mg, following subtherapeutic INR. The first dose increase was nine days after initiating ribavirin + sofosbuvir. The authors postulate a drug interaction between ribavirin (due to increased factor VII synthesis) + sofosbuvir (due to improvements in hepatic health and subsequent increase in CYP3A4) and warfarin.

A case was reported of a 63-year-old man who presented to the Emergency Department with leg pain and a cold foot. He was taking warfarin (102.5 mg, weekly) after a history of femoral-popliteal bypass surgery and had started sofosbuvir/velpatasvir (400/100 mg, once daily) 14 days before presentation. Tests revealed a fall in INR from 3.4 when sofosbuvir/velpatasvir was started to 2.1, and graft thrombosis. Infusion of alteplase reversed his symptoms and he was discharged and switched from warfarin to enoxaparin. He achieved SVR12 and had no further issues with anticoagulation therapy after discontinuing sofosbuvir/velpatasvir. The authors hypothesise a drug interaction between sofosbuvir/velpatasvir and warfarin.