Amfebutamone/bupropion for smoking cessation: new preparation. Nicotine replacement therapy is safer.

(1) For smokers who want to quit and who qualify for pharmacological support, the various forms of nicotine replacement therapy available in France yield a one-year cessation rate of about 14-18%, compared to about 10% with placebo. (2) Amfebutamone (also known as bupropion) is structurally related to an amphetamine psychostimulant. (3) The clinical file mainly contains data from a dose-finding study, two placebo-controlled trials, and a trial comparing amfebutamone + transdermal nicotine with amfebutamone + transdermal placebo. (4) It has not yet been shown that the approved dose regimen of 300 mg/day is more effective than 150 mg/day, or that the treatment period of 7-9 weeks is optimal. (5) Compared to placebo, the one-year cessation rate was only about 13% higher (absolute value) in one trial, much less in the dose-finding study (3%), and not determined in the other two trials. The trial comparing amfebutamone with nicotine suffers from too many methodological weaknesses to show any difference in the efficacy of the two drugs. There has been no specific assessment of amfebutamone in patients with coronary heart disease. (6) There is no basis for combining amfebutamone with nicotine replacement therapy, as there is no evidence of higher efficacy. Furthermore, cardiovascular risk may be increased. (7) Amfebutamone can have serious adverse effects: the estimated risk is approximately 0.1% for convulsions and 3% for potentially severe hypersensitivity reactions. The adverse effects seem to be similar to those of appetite-suppressant amphetamines, including insomnia, weight loss and hypertension. The possible risk of heart valve disease has not been ruled out, because echocardiographic follow-up studies have not been done. (8) Potential adverse effects and drug interactions should contraindicate the use of amfebutamone by patients with a history of cardiovascular, neurological or psychiatric disorders. (9) In practice, when someone needs drug support to quit smoking, nicotine replacement therapy should be tried first.