Bioequivalence of Coumadin and Marevan

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Editor, – The debate about the existence of two brands of warfarin has centred around the bioequivalence of the two products.1,2 We have noticed a difference in bioavailability of up to 26% between brands of warfarin in one individual in a comparative study.3 No such study has been performed in Australia; however, to cover the possibility, the PBAC has recommended a warning note accompany PBS listings for warfarin brands and strengths.2

The Boots Company has suggested that a lack of testing of these products does not imply that they are not bioequivalent, but that caution should be exercised if brand substitution occurs. Our experience with a single patient indicates that the brands are not bioequivalent. The patient was on a dose of 4 mg of warfarin, initially provided by 1 x 1 mg, 1 x 3 mg Marevan, and had an INR = 2.7. Upon completion of that supply, the patient was given Coumadin (2 x 2 mg) and subsequently presented with an INR = 4.4. After questioning, we established that the patient was well and that brand substitution had occurred. The Coumadin was stopped and replaced with Marevan and the INR returned to an acceptable level. It was fortunate that the initial INR was not higher as the brand substitution could easily have placed the patient at risk of haemorrhage. It is reasonable to suggest from this patient that the brands are not bioequivalent. There is a report of similar instability in 15 patients who had their brand of warfarin substituted.4

As brand substitution is not allowed for warfarin products on the Pharmaceutical Benefits Scheme, hospital and community pharmacists should be wary about generic prescriptions and involve themselves in educating doctors and patients. Not only should they check which brand the patient is currently on, but also stress to the patient the importance of staying on that particular brand, in order to avoid possible variations in anticoagulant status.

V. Williams
Haematology Department
R. Vining
Pharmacy Department
Women's and Children's Hospital
Adelaide, S.A.


  1. Healy DF. Warfarin tablets [letter]. Aust Prescr 1996;19:6-7.
  2. Fry FK. Warfarin tablets [letter]. Aust Prescr 1997;20:33.
  3. Muller FO, Steyn JM, Hundt HK, Luus HG. Warfarin bio-availability: a comparison of 4 products. S Afr Med J 1988;74:566-7.
  4. Richton-Hewett S, Foster E, Apstein CS. Medical and economic consequences of a blinded oral anticoagulant brand change at a municipal hospital. Arch Intern Med 1988;148:806-8.