Fenfluramine Anorexients and Anesthesia

Abstract

Nearly one out of every three adults in the United States is obese and the prevalence is increasing according to a 1995 report by the Institute of Medicine (1). Obesity, in combination with other risk factors, is responsible for the deaths of an estimated 300,000 Americans each year (2). Similar trends have been noted worldwide (3). The mainstay for weight reduction is diet modification and exercise. Appetite suppressant drugs (anorexients) are considered adjuncts to diet and behavior modification and exercise, and have traditionally been indicated only for short term use (4). Recently however, controlled clinical trials have demonstrated longer term weight reduction when anorexient medications are used in conjunction with diet modification and exercise (5,6). News of this data, along with the marketing of the newest prescription anorexient dexfenfluramine (Redux® Wyeth-Ayerst Laboratories), will undoubtedly cause a resurgence in the use of diet pills. Anesthesiology practitioners are likely to encounter a increasing number of patients who are taking anorexients and therefore need to be knowledgeable about the potential risks of anesthesia in patients taking these agents. Fenfluramine (Pondimin®AH Robins) and dexfenfluramine are anorexients that induce the release and inhibit the reuptake of serotonin (7,8). Elevated brain serotonin levels are associated with early satiety and appetite suppression. Fenfluramine, is a racemate of the dextro-and levo-rotatory isomers of fenfluramine and is a commonly prescribed anorexient. According to the manufacturer’s prescribing information the drug is contraindicated in patients undergoing general anesthesia because of a possible interaction with halogenated anesthetics. Because the halflife is 20 hours, the drug should be discontinued at least 5 days prior to the administration of anesthesia. Dexfenfluramine, the biologically active dextro-rotatory stereoisomer of fenfluramine, has been available in Europe for many years and was recently approved by the FDA in the United States (9). Unlike fenfluramine however, dexfenfluramine is not contraindicated in patients undergoing anesthesia. The manufacturer’s prescribing information advises that fenfluramine is contraindicated in patients undergoing general anesthesia because of a single case report of a fatal cardiac arrest following the induction of anesthesia with halothane in a patient who had been taking fenfluramine prior to surgery (10)(12). It was postulated that fenfluramine may have had a catecholamine-depleting effect that may have led to cardiovascular collapse upon exposure to halothane. In vivo experiments in rabbits receiving fenfluramine and halothane seemed to be consistent with this hypothesis (10). However, neither the clinical information presented in the case report nor the design of the drug interaction experiment were adequate to answer the question of whether or not a interaction exists (11). Nevertheless, the manufacturer recommends that potent anesthetic agents be administered with caution to patients taking fenfluramine and if general anesthesia cannot be avoided, full cardiac monitoring and facilities for instant resuscitation measures are a minimum necessity (12). More recently, a letter from the Texas Society of Anesthesiologists concerning the administration of anesthesia to patients taking fenfluramine warned of the potential medical-legal risks (13). Since the initial case report by Bennett and Eltringham however, there have been no further reports of adverse events related to a anesthetic interaction with either fenfluramine or dexfenfluramine and unfortunately no definitive drug interaction studies have been conducted. Information obtained under the Freedom of Information Act from the U.S. Food and Drug Administration also failed to reveal any additional Fenfluramine Anorexients and Anesthesia 2 of 5 reports of adverse events related to the use of fenfluramine and anesthesia. Thus the question remains: Is there a drug interaction between fenfluramine and anesthetic