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ANTICOAGULATION

Are Brand-Name and Generic Warfarin Interchangeable? Multiple N-of-1 Randomized, Crossover Trials

Trainee, Centre for Evaluation of Medicines, St. Joseph's Healthcare, Hamilton, Ontario, Canada; PhD Student, Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario

Anne M Holbrook, MD PharmD MSc FRCP(C)

Director, Division of Clinical Pharmacology, Department of Medicine, McMaster University, Hamilton; Senior Scientist, Centre for Evaluation of Medicines, St. Joseph's Healthcare

Lisa Dolovich, PharmD

Scientist, Centre for Evaluation of Medicines; Ambulatory Care Pharmacotherapy Specialist, St. Joseph's Healthcare

Charles Goldsmith, PhD

Head of Biostatistics, Centre for Evaluation of Medicines, St. Joseph's Healthcare; Professor, Department of Clinical Epidemiology and Biostatistics, McMaster University

Lehana Thabane, PhD

Biostatistician, Centre for Evaluation of Medicines, St. Joseph's Healthcare; Assistant Professor, Department of Clinical Epidemiology and Biostatistics, McMaster University

James D Douketis, MD FRCP(C)

Division of General Internal Medicine, St. Joseph's Healthcare; Associate Professor, Department of Medicine, McMaster University

Mark A Crowther, MD FRCP(C)

Hematologist, St. Joseph's Healthcare; Associate Professor, Department of Medicine, McMaster University

Shannon M Bates, MD MSc FRCP(C)

Department of Medicine, McMaster University

Jeffrey S Ginsberg, MD FRCP(C)

Hematologist, Hamilton Health Sciences; Professor, Department of Medicine, McMaster University

Reprints: Ms. Pereira, Centre for Evaluation of Medicines, 105 Main St. E. Level 1, Hamilton, ON, L8N 1G6 Canada, fax 905/528-7386, j.pereira{at}utoronto.ca

BACKGROUND: Warfarin is a commonly used anticoagulant in North America. Several generic formulations have been approved, raising concern over the safety and efficacy of these products compared with brand-name Coumadin.

OBJECTIVE: To ensure that generic warfarin products can be safely interchanged with Coumadin.

METHODS: Multiple n-of-1 randomized, double-blind, crossover trials switched outpatients (N = 7) between a generic warfarin formulation (Apo-warfarin) and Coumadin over 30 weeks. Study patients took each drug for five 3-week periods, with international normalized ratio (INR) measurements taken twice per period. Inter- and intrapatient differences between generic warfarin and Coumadin were compared, and overall study patient results were compared with those of a Coumadin control group.

RESULTS: There were no differences between warfarin products in terms of mean INR results or number of dosage adjustments required. There also was no difference in INR variation based on warfarin formulation (p > 0.69), nor was a patient and warfarin interaction found (p > 0.81). The INR results were not influenced by whether patients were maintained on Coumadin only (control group) or interchanged between Coumadin and generic warfarin (p = 0.98).

CONCLUSIONS: It appears that patients can safely and effectively switch between generic warfarin and Coumadin.

Key Words: generic warfarin, bioequivalence, interchangeability

Published Online, May 24, 2005. www.theannals.com, DOI 10.1345/aph.1G003