Temporal decline in filling prescriptions for terfenadine closely in time with those for either ketoconazole or erythromycin*

Abstract

Temporal changes in the rates of filling terfenadine prescriptions within 2 days of those for either oral erythromycin or oral ketoconazole were described with use of paid pharmacy claims data from 1988 through 1994 in state Medicaid programs from Michigan and Ohio and in a large health maintenance organization. There were rapid and significant declines in the rates of filling prescriptions for either erythromycin or ketoconazole within 2 days of prescriptions for terfenadine in all three databases that coincided with 1992 publicity about the cardiovascular risk of terfenadine. These findings suggest that the use of terfenadine with contraindicated medications has declined in response to relabeling and publicity concerning the safe use of terfenadine. Further study is necessary to estimate the absolute level of concurrent use of terfenadine with contraindicated medications.

Impact of FDA Drug Risk Communications on Health Care Utilization and Health Behaviors

“…For example, several studies suggested the largest declines in cisapride co-prescribing occurred following the FDA’s third such warning (20–23), although not all studies indicated such a change (24). Declines in terfenadine co-prescribing also occurred although the largest effects were not observed until 18 months or more following the initial warnings (25–27). Only one study concluded there was an increase in terfenadine co-prescribing between 1991 and 1992, although the authors examined absolute rather than relative co-prescribing events (28).…”

Drug-Induced Prolongation of the QT Interval

“…However, multiple attempts by regulatory agencies and drug companies to limit the administration of dangerous combinations, such as cisapride and erythromycin, have been only transiently successful. [75][76][77] Prescribers should recognize that most drugs have multiple, and often unanticipated, actions. In addition, even drugs that are designed to interact with a single molecular target act in a complex biologic milieu.…”

Drug-Induced Long QT Syndrome

“…The identification of a very small number of cases of diLQTS, however, markedly upset the risk-benefit calculations for the drug: the publically promulgated regulatory view was that the drug was prescribed for a nonlethal indication (allergies) and that even a small risk of a fatal adverse drug reaction was therefore unacceptable. Attempts by regulatory authorities (Burkhart et al, 1997) to make physicians and the public aware of the dangers of drug interactions with terfenadine, including black box warnings and educational programs, were ultimately unsuccessful (Cavuto et al, 1996;Thompson and Oster, 1996;Woosley, 2000) and when fexofenadine was approved for therapy, terfenadine was withdrawn.…”