Maja Hellfritzsch1, Jette Rathe2, Tore Bjerregaard Stage1, Steffen Thirstrup3,4, Erik L Grove5, Per Damkier1,2, Anton Pottegård1. 1. Clinical Pharmacology, Department of Public Health, University of Southern Denmark, Denmark. 2. Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Denmark. 3. Department of Drug Design and Pharmacology, University of Copenhagen, Denmark. 4. NDA Advisory Services Ltd, United Kingdom. 5. Department of Cardiology, Aarhus University Hospital, Denmark.
Abstract
PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis. METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105,751 warfarin users, filling a total of 1,539,640 prescriptions for warfarin (2.5% for generic warfarin). This constituted 89.0% of all warfarin prescriptions in Denmark during the study period. We observed 19,362 switches to generic warfarin during the study period. The adjusted hazard ratio for excessive anticoagulation following a recent switch from branded to generic warfarin was 1.1 (95%CI, 0.8-1.4). The result was robust within subgroups and several sensitivity analyses. CONCLUSION: Switching from branded to generic warfarin is not associated with an increased risk of hospitalization with excessive anticoagulation. However, a minor excess risk of transient INR increase cannot be excluded. Pharmacoepidemiological studies provide an effective method for swift evaluation of hypotheses generated by ADR-reports.
PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis. METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105,751 warfarin users, filling a total of 1,539,640 prescriptions for warfarin (2.5% for generic warfarin). This constituted 89.0% of all warfarin prescriptions in Denmark during the study period. We observed 19,362 switches to generic warfarin during the study period. The adjusted hazard ratio for excessive anticoagulation following a recent switch from branded to generic warfarin was 1.1 (95%CI, 0.8-1.4). The result was robust within subgroups and several sensitivity analyses. CONCLUSION: Switching from branded to generic warfarin is not associated with an increased risk of hospitalization with excessive anticoagulation. However, a minor excess risk of transient INR increase cannot be excluded. Pharmacoepidemiological studies provide an effective method for swift evaluation of hypotheses generated by ADR-reports.
Authors: Ameet Sarpatwari; Joshua J Gagne; Zhigang Lu; Eric G Campbell; Wendy J Carman; Cheryl L Enger; Sarah K Dutcher; Wenlei Jiang; Aaron S Kesselheim Journal: J Gen Intern Med Date: 2019-01-10 Impact factor: 5.128