Please Circulate to All Prescribers and Pharmacists

Dear Health Care Provider:

As you know, the recent listing of warfarin sodium products with AB equivalence ratings in the Orange Book has been followed by a great deal of public controversy. In addition, misinformation has circulated concerning the Massachusetts state formulary. The controversy and misinformation have raised the concerns of prescribers, pharmacists, and patients regarding the interchange of these products. This letter is intended to clarify the issues and provide correct information concerning the state formulary.

Pharmaceutical and medical expertise at the state and federal levels ensures that safe and effective equivalent drug products are available for patients. The U.S. Food and Drug Administration (FDA) stated on March 26, 1997 that Warfarin Sodium Tablets manufactured by Barr Laboratories, Inc. are "bioequivalent and therefore, therapeutically equivalent to the listed drug (Coumadin® Tablets)" manufactured by DuPont Merck Pharmaceutical Co. On the matter of equivalence determinations for drugs with narrow therapeutic ratio, FDA has stated that "because of FDA's strict bioequivalence criteria, we believe that drugs do not fall into discrete groups that would allow one to consider NTI [narrow therapeutic index] drugs as being clearly different from other drugs for purposes of therapeutic substitution." The FDA has also stated that "if one therapeutically equivalent drug is substituted for another, the physician, pharmacist and patient have FDA's assurance that the physician should see the same clinical results and safety profile."

In addition to the FDA's analysis, the Drug Formulary Commission is charged by state law with evaluating bioequivalence and therapeutic equivalence of drug products. The Commission meets as needed to consider petitions to add or remove products from the formulary and to review formulary matters. Concerning drug products with narrow therapeutic ratios, the Commission has not removed any federally "A"-rated products. Ultimately, health care providers are responsible for using sound professional judgment in selecting the appropriate drug product for each patient. Prescribers in their professional judgment may specify "no substitution" on a prescription. And for an interchangeable drug, pharmacists use their professional judgment in dispensing a prescription and in communicating with the prescriber about cases of midstream interchange.

For information on interchange and state formulary laws, regulations, policies, procedures, and other matters please contact the Drug Control Program directly at (617) 983-6700 or visit the Program's Website at www.state.ma.us/dph/dcp.


This information is provided by the Drug Control Program within the Department of Public Health.