warfarinfo

Warfarin Institute of America

DEDICATED TO YOUR HEALTH SINCE 2000

COUMADIN OR GENERIC WARFARIN, IS THERE A DIFFERENCE?

For more than forty years, Coumadin was the only brand of warfarin marketed in the United States. When generic equivalents of many drugs began coming to market in the 1970s, the technology did not exist to make a generic warfarin that was the equal of Coumadin. The various companies that owned the brand name Coumadin over the years needed to do little to market the product. Mostly they just proclaimed (rightly) that it was a drug that needed to be maintained in a narrow therapeutic range so there was no reason to even seek a generic equivalent. However, in the 1990s, when it became apparent that a generic that was as good as Coumadin, was likely to become a reality, DuPont Pharma vastly increased its sales and legal staffs and speakers bureau. The often repeated message was to not take a chance with a "Narrow Therapeutic Index" drug.

Trouble began to appear when the United States Food an Drug Administration in its "Orange Book" gave the generic products an AB equivalence rating. This meant that laboratory studies were unable to distinguish any difference between Coumadin and generics. Now there were differences of opinion between DuPont's people and laboratory staffs. What happened when there were head-to-head studies in real patients between the two products?

At a 1998 meeting of the American Society of Health-system Pharmacists, Swenson and Fundak on a group of 210 patients who were divided into two groups. One-half switched to generic warfarin and the others remained on Coumadin. The before-and-after differences in INR between the groups were small and of no clinical significance. This was of particular importance to the HMO doing the study since they were responsible for the entire health-care costs of the patients. Had there been any increase in laboratory testing, Emergency Room visits, etc it would have been to their economic disadvantage. By the time they published their report in 2000, the HMO had switched approximately 4,400 patients to generic warfarin with a 97% success rate. Neutel and Smith conducted another study about this same time that concluded that the products could be safely interchanged. This author reported on these two studies in a review article in 1999 and to date (3-15-03), I know of no challenge to their results.

In 2002, Milligan et al reported on another study of switching between products by an HMO. Their method was slightly different. They switched 182 people from Coumadin to generic warfarin. At then end of the study they collected data from eight months prior to the switch until ten months after the switch. The data included INR control, frequency of testing, the number of times that doses had to be changed, rate of thrombotic events and rate of hemorrhagic events. There were no statistically significant differences.

Witt et al reported on the largest warfarin switch study to date. At their HMO, 2,299 patients were followed after switching from Coumadin to generic. In the control period before the switch, 65.9% of the people had INRs in the therapeutic range. In the study period after the switch, 63.3% of the people had INRs in the therapeutic range. This was not considered a clinically significant difference. (By comparison, this Mr. Lodwick's clinic typically has about 60% of patients in the therapeutic range each month.) The authors conclude that supplemental INR monitoring is warranted when one product is substituted for another to allow for timely detection of those patients who experience significant changes in anticoagulation response.

Are there any studies that show that Coumadin is better than generic warfarin? A search of Medline for articles published between January 1, 1996 to March 15, 2003 (limited to humans and with abstracts) containing the search words "warfarin AND generic" did not show any.

There are some case reports in the peer-reviewed literature uncovered by the above search described above. Wagner and Dent reported on a 61-year-old man switched from Coumadin to generic who suffered epistaxis. When the epistaxis occurred, the patient was on vacation. It is this authors impression that going on vacation and having houseguests are the two most common life-style changes leading to INRs out of range. Hope and Havrda reported on two cases of patients with INRs below the therapeutic range after switching to generic. There is no doubt that some patients will experience problems. Careful monitoring is justified.

Is there a difference between Coumadin and generic warfarin? DuPont agreed to a $44.5 million settlement for overly aggressively marketing Coumadin after the FDA found that there was generic equivalence. Henderson and Esham concluded, "misinformation and myths persists regarding the adequacy and proven reliability of the FDA's determination of bioequivalence of these products."

Here is the latest episode. Everyone using the national health service of Israel was required to switch from branded to the same generic version of warfarin. Halkin et al studied the warfarin dosing requirements of 975 people. They found that after the switch people required warfarin doses that averaged 26.5% higher. But there were no excess hospital admissions for these people. What was not given in the abstract of this article that I read was whether or not the generic and the brand were manufactured under the same set of standards. If they were, was there actual testing of the tablets, as they were marketed, to prove that they were meeting those standards?

The most definitive study that will ever be done on this took place in the province of Ontario, Canada and was reported by Paterson et al.. On June 7, 2001 everyone in the province taking Coumadin was switched to generic warfarin (except for about 10% of the people who had to pay 70% more to continue on the branded product). A study of 22,926 people on Coumadin during the forty months prior to the switch and 36,724 people in the nine months after the switch found no changes in the rate of INR testing, no changes in the rate of hospitalizations for major bleeding and no changes in the rate of hospitalizations for clotting-type strokes. IN THE OPINION OF THIS EDITOR, AFTER THE DATE OF PUBLICATION OF THE STUDY BY PATERSON IN 2006, ANYONE WHO CLAIMS THAT THERE IS A DIFFERENCE BETWEEN COUMADIN AND GENERIC WARFARIN SIMPLY DOES NOT KNOW WHAT THEY ARE TALKING ABOUT.

References:

Swenson CN, Fundak G. Observational cohort study of switching warfarin sodium products in a managed care organization. Am J Health-syst Pharm 2000;57:452-5.

Neutel JM, Smith DHG. A randomized, crossover study to compare the efficacy and tolerability of Barr warfarin sodium to the currently available Coumadin©. Cardiovascular Reviews and Reports 1998;19:49

Lodwick A. Warfarin Therapy: A Review of the Literature since the Fifth American College of Chest Physicians' Consensus Conference on Antithrombotic Therapy. Clin Appl Thrombosis/Hemostasis 1999;5:208-15.

Milligan PE et al Substution of generic warfarin for Coumadin in an HMO setting. Ann Pharmacother 2002;36:764-8.

Witt DM et al Evaluation of the clinical and economic impact of a brand name-to-generic warfarin sodium conversion program. Pharmacotherapy 2003;23:360-8

Wagner JL, Dent LA. Epistaxis associated with elevation of INR in a patient switched to generic warfarin. Pharmacotherapy 2000;20:240-3.

Hope, KA, Havrda DE. Subtherapeutic INR values associated with a switch to generic warfarin. Ann Pharmacother 2001;35:183-7

Henderson JD, Esham RH. Generic substitution: issues for problematic drugs. South Med J 2001;94:1235.

Halkin H, et al. Increased warfarin doses and decreased international normalized ratio response after nationwide generic switching. Clin Pharmacol Ther. 2003;74:215-221.

Paterson et al. Clinical consequences of generic warfarin substitution. JAMA. 2006;296:1967-71.

SEE A CATALOG OF PUBLICATIONS AVAILABLE FROM LODWICK CREATIONS, LLC.

LEARN HOW YOU CAN BECOME LISTED ON THE HONOR ROLL OF SUPPORTERS AND TAKE ADVANTAGE OF THE BENEFITS

REQUEST A MEDICATION CONSULTATION

IF YOU HAVE FOUND THE INFORMATION ON THIS PAGE USEFUL, PLEASE HELP ASSURE ITS CONTINUED AVAILABILITY.

Home Back to interactions list

Contact Mr. Lodwick at allodwick@earthlink.net

Last updated February 18, 2007