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Influence of Successful Chronic Hepatitis C Virus Treatment with Ledipasvir/Sofosbuvir on Warfarin Dosing Requirements in Four Veterans
Author(s) -
Britnell Sara R.,
Willets Amy E.,
Vanderman Adam J.,
Woodard Catherine L.,
Britt Rachel B.
Publication year - 2016
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1845
Subject(s) - sofosbuvir , ledipasvir , medicine , warfarin , ribavirin , dosing , hepatitis c , hepatitis c virus , atrial fibrillation , virology , virus
Study Objective To describe international normalized ratio (INR) trends and warfarin dosage adjustments required for four veterans who were receiving warfarin therapy and started treatment for hepatitis C virus (HCV) with ledipasvir/sofosbuvir with or without ribavirin. Design Case series. Setting Pharmacist‐led anticoagulation clinic in a Veterans Affairs Health Care System. Patients Four patients aged 59–66 years who were receiving warfarin and had stable, therapeutic INRs and started ledipasvir/sofosbuvir therapy with or without ribavirin for HCV infection. Measurements and Main Results All four patients developed subtherapeutic INRs after the addition of ledipasvir/sofosbuvir with or without ribavirin. An increase in weekly warfarin dose ranging from 14–67% was required, with changes in warfarin doses starting 2–3 weeks after ledipasvir/sofosbuvir initiation. Two patients required dose reductions after HCV treatment completion, whereas the other two did not. Use of the Drug Interaction Probability Scale indicated that the interaction between warfarin and ledipasvir/sofosbuvir was doubtful (score of 1 [two patients]) or possible (score of 4 [two patients]). The mechanism of this interaction is unknown but may be related to improvements in hepatic function during HCV treatment. Conclusion To our knowledge, this is the first case series describing a possible drug interaction between warfarin and ledipasvir/sofosbuvir (with or without ribavirin). Close monitoring is warranted when ledipasvir/sofosbuvir is initiated in patients receiving anticoagulation therapy with warfarin, especially those with evidence of cirrhosis prior to treatment. This is particularly important in the first month after starting treatment and the first month after completion. Failure to monitor and achieve therapeutic INR after HCV therapy completion may have the potential to result in adverse outcomes.