Serious Adverse Reactions of Bupropion for Smoking Cessation: Analysis of the French Pharmacovigilance Database from 2001 to 2004

• Published in: Drug safety 2008-01, Vol.31 (11), p.1017-1026
• Main Authors: Beyens, Marie-Nöelle, Guy, Claire, Mounier, Genevieve, Laporte, Sylvie, Ollagnier, Michel
• Format: Article
• Language: English
• Subjects: 2001 AD; Adolescent; Adult; Adverse and side effects; Aged; Analysis; Angioedema - chemically induced; Angioedema - epidemiology; Antidepressive Agents, Second-Generation - adverse effects; Antidepressive Agents, Second-Generation - therapeutic use; Biological and medical sciences; Bupropion; Bupropion - adverse effects; Bupropion - therapeutic use; Cerebrovascular Disorders - chemically induced; Cerebrovascular Disorders - epidemiology; Clinical trial. Drug monitoring; Complications and side effects; Databases, Factual; Death, Sudden, Cardiac - epidemiology; Depression, Mental; Drug Eruptions - epidemiology; Drug Overdose - epidemiology; Drug Safety and Pharmacovigilance; Drug therapy; Drugs; Female; France - epidemiology; General pharmacology; Humans; Male; Medical sciences; Medicine; Medicine & Public Health; Mental Disorders - chemically induced; Mental Disorders - epidemiology; Mental Disorders - psychology; Middle Aged; Myocardial Ischemia - chemically induced; Myocardial Ischemia - epidemiology; Nervous System Diseases - chemically induced; Nervous System Diseases - epidemiology; Original Research Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Product Surveillance, Postmarketing; Risk Factors; Seizures - chemically induced; Seizures - epidemiology; Serum Sickness - chemically induced; Serum Sickness - epidemiology; Smoking Cessation; Smoking cessation programs; Suicide - statistics & numerical data; Suicide, Attempted - statistics & numerical data; Tobacco, tobacco smoking; Toxicology; Young Adult
• ISSN: 0114-5916; 1179-1942
• DOI: 10.2165/00002018-200831110-00006

Background: Bupropion was the first alternative to nicotine replacement therapy in the pharmacological treatment for smoking cessation. Its safety profile has been monitored in France via spontaneous reporting. Objective: To describe all serious adverse reactions (SARs) reported in France since the marketing authorization for bupropion in September 2001, and to analyse risk factors for these SARs. Design: We collected all spontaneous reports of adverse reactions to bupropion received by all French Regional Pharmacovigilance Centres and by GlaxoSmith-Kline, the manufacturer of bupropion, during the first 3 years of marketing of this agent. We identified the characteristics of the population to whom bupropion was prescribed from the Thales database, which contains information obtained from a representative sample of general practitioners in France. We then compared the population with SARs with the population prescribed the drug (exposed population) to identify possible risk factors such as sex, age and daily dose for the most frequent SARs. Results: Bupropion was prescribed to 698 000 patients during the first 3 years of marketing in France. In these patients, 1682 cases of adverse reactions were reported; 28% of these involved SARs, mainly cutaneous or allergic reactions (31.2%), including angioedema and serum sickness-like reactions. Serious neurological reactions were frequent (22.5%), mostly comprising seizures; however, questioning revealed that almost half of these patients had a history of seizures or other risk factors. Of the serious neuropsychiatric adverse events reported (17.3%), suicide attempts/suicides were a cause for concern, although risk factors (history of depression, suicide attempts, etc.) were described for 66% of patients experiencing these events. Patients reporting angioedema and serum sickness-like reactions, and those involved in suicide attempts/suicides, were significantly younger than the exposed population. A dose-dependent effect was also apparent for angioedema and for seizures. Cardiovascular SARs, such as ischaemic heart disease (10.1%) or sudden death (2.3%), were very often associated with preexisting coronary artery disease induced by smoking. All these SARs occurred within a median of 12–14 days after drug initiation. Conclusion: To ensure safer use of bupropion, health professionals must respect the strict contraindications and warnings about use of this drug in patients with a history of seizures. Seizures, angioede