Critical Therapeutic Categories: a Contraindication to Generic Substitution?

All 50 states either permit or require a pharmacist to substitute a generic drug for a prescribed brand-name drug unless the physician specifically notes on the prescription form that substitution is not to be made. In certain critical therapeutic categories and for certain patient populations, each substitution poses the risks of treatment failure and of increased toxicity. The therapeutic categories include cardiovascular drugs, psychotropic agents, and anticonvulsants. Additional potential therapeutic categories include cardiovascular drugs, psychotropic agents, and anticonvulsants. Additional potential therapeutic categories include low-dose oral contraceptives, bronchodilating agents, oral diuretics, and oral anticoagulants. The populations at risk include debilitated or elderly patients with abnormal gastrointestinal, renal, or hepatic function. The FDA's approach to approval of generic drugs, based primarily on the demonstration of bioequivalence, is considered by many professionals as likely to result in excessive variability among treated patients. Depending on the particular rule defining bioequivalence, indiscriminate switching among generic versions of a brand-name drug potentially could result in 40% to 60% differences in rate or extent of absorption. For drugs that require careful titration to assure efficacy and lack of toxicity, such variability can have important consequences. The FDA is now reviewing its policies for approval of generic drugs. Until the matter is resolved, however, caution should be exercised when prescribing or dispensing drugs that can be substituted. Indiscriminate switching among generic products should be avoided, especially for drugs in the critical therapeutic categories and for drugs prescribed for elderly or debilitated patients.