Physicians underestimate the frequency of generic carbamazepine substitution: results of a survey and review of the problem

Abstract

Antiepileptic drugs (AEDs) possess a narrow therapeutic range, and generic substitution may lead to breakthrough seizures and adverse events. Prescribers of AEDs may be unaware how frequently generic substitution actually occurs. Surveys were administered to 845 physicians at the 2001 American Epilepsy Society (AES) meeting and the 2001 American Academy of Neurology (AAN) meeting. Two hundred fifty-eight physicians responded to the AES survey and 587 physicians to the AAN survey. Questions were multiple choice and displayed on a computer screen. Among other questions, physicians were asked: (1) What percentage of patients are substituted with a generic short-acting carbamazepine in the US annually? (2) Are you comfortable with patients receiving multiple formulations of generic carbamazepine? Responses to the first question were compared to the actual rate of generic substitution determined by an independent audit of 1,036,000 Tegretol prescriptions. In the AES survey, 10.9% of respondents estimated that 10% of patients had carbamazepine generic substitutions, 41.9% estimated a 30% substitution rate, 30.2% estimated a 50% rate, and 17.1% estimated a 70% rate. The AAN respondents had similar estimates: 17.5% guessed a 10% rate, 40.0% a 30% rate, 30.2% a 50% rate, and 12.3% a 70% rate. In the AES survey, 86.4% of respondents were not “comfortable with patients receiving multiple formulations of generic carbamazepine.” Similarly, in the AAN survey, 80.3% of respondents did not endorse generic substitution of carbamazepine. An independent audit of generic substitutions revealed that of 766,000 prescriptions for 200 mg of Tegretol, pharmacists substituted 551,000 (72%) with generic carbamazepine. Of 199,000 prescriptions for 100 mg of Tegretol, 140,000 (70%) were filled with a generic. Of 71,000 prescriptions for Tegretol 100 mg/5 ml suspension, 10,000 (14%) were filled with a generic. The overall substitution rate was 701,000/1,036,000 (68%), much higher than estimated by the majority of surveyed attendees. In conclusion, most surveyed physicians at the 2001 AES and AAN meetings significantly underestimated the number of generic substitutions that occur for brand name short-acting carbamazepine. Given the potential for breakthrough seizures and adverse events related to generic substitution, physicians need to be more vigilant in their prescription-writing practices to prevent unwarranted generic substitution.