title: Evaluation of a Potential Interaction Between New Regimens to Treat Hepatitis C and Warfarin.
abstract: New regimens to treat hepatitis C virus infection have expanded the eligible patient population to include more patients receiving concurrent warfarin. The primary objective of this study was to assess whether a drug interaction occurs when these regimens are added to warfarin therapy.
  
  
  
  This was a retrospective cohort design using a nationwide database of the Veterans Affairs Health System. Patients on warfarin therapy treated with sofosbuvir or ombitasvir, paritaprevir-ritonavir, and dasabuvir (OBV-PTV/r-DSV) from March 2014 through October 2015 were identified. The warfarin dose response was calculated using a warfarin sensitivity index (WSI) defined as the steady-state INR divided by the mean daily warfarin dose. The primary outcome was the change in WSI from hepatitis C treatment initiation to completion.
  
  
  
  The final sample consisted of 271 patients. The WSI decreased 23% from a mean baseline value of 0.53 to 0.39 (decrease of 0.14; 95% CI = 0.11 to 0.16; P < 0.001). OBV-PTV/r-DSV produced a significantly greater decrease than any sofosbuvir regimen. Concurrent ribavirin accounted for an additional decrease in warfarin sensitivity of -0.09 (95% CI = -0.06 to -0.12; P < 0.001). The percentage of subtherapeutic INR results increased from 26% prior to hepatitis C treatment to 58% during treatment.
  
  
  
  Results indicate a clinically significant reduction in warfarin dose-response when hepatitis C treatment regimens were added to warfarin. They were most profound with OBV-PTV/r-DSV. Ribavirin was associated with an additive effect. Clinicians should be aware of this potential drug interaction to closely monitor and minimize subtherapeutic levels of anticoagulation.
authors.affiliation: 1 Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: DeCarolis
authors.affiliation: 1 Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Westanmo
authors.affiliation: 2 University of Minnesota, Minneapolis, MN, USA.
authors.forename: Yi-Chie
authors.initials: YC
authors.lastname: Chen
authors.affiliation: 1 Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Boese
authors.affiliation: 1 Minneapolis VA Health Care System, Minneapolis, MN, USA.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Walquist
authors.affiliation: 2 University of Minnesota, Minneapolis, MN, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Rector
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000998:Antiviral Agents; D014859:Warfarin
keywords: anticoagulants; anticoagulation; antivirals; cytochrome P-450 interactions; drug interactions; gastroenterology; hepatitis C; pharmacokinetics; therapeutic monitoring; warfarin