Evaluation of the safety of bupropion (Zyban) for smoking cessation from experience gained in general practice use in England in 2000.

Background: Bupropion (Zyban) is the first new pharmacological treatment for smoking cessation to be introduced since nicotine replacement therapy. In smoking cessation trials, it has been associated with minimal side effects. A range of suspected adverse drug reactions (ADRs) were reported via the spontaneous reporting system following its use in smoking cessation.

Aim: To examine the safety of bupropion used in general medical practice in England as a treatment for cessation of smoking.

Objectives: To quantify the incidence of events that were reported for patients prescribed bupropion; and to identify any previously unrecognised ADRs.

Methods: A post-marketing observational cohort study was conducted using the methodology of prescription-event monitoring (PEM). Exposure data were derived from the first prescription dispensed for patients whose prescription details were processed by the Prescription Pricing Authority in August 2000. Outcome data were derived from 'green form' questionnaires (GFs) sent to general practitioners (GPs) at least 6 months following the first prescription issued. Incidence densities (IDs) were calculated for events reported per 1000 weeks of patient treatment and ID differences between time periods analysed. Events of interest were followed up by postal questionnaire sent to GPs. All-cause and condition-specific mortality up to 12 weeks after starting bupropion were compared through indirect standardisation between the PEM cohort and Cancer Prevention Study-II (USA) (CPS-II) data.

Results: GF response rate was 48.1%, with 11,735 GFs containing useful data - of these patients, 5695 (48.5%) were male (median age 47 years, range 16-88 years) and 6009 (51.2%) were female (median age 47 years, range 16-87 years). Age was recorded for 4092 (34.9%) of the cohort of 11,735 after follow-up. There were 566 events in 350 patients reported by GPs as ADRs to bupropion. GPs reported 10,200 reasons for stopping bupropion among 9056 patients. The highest ranked clinical events (by ID for weeks 1-6 of treatment) were; 'insomnia' ( n=308), 'nausea/vomiting' ( n=243) and 'dizziness' ( n=185). Bupropion was taken in the first trimester of 12 pregnancies and the outcome ascertained in eight cases - five live births (no congenital abnormalities reported), two therapeutic terminations and one intrauterine death (no further details). The standardised mortality ratio (SMR) for all-cause mortality up to 12 weeks after starting bupropion was 0.77 (95% CI: 0.42, 1.28).

Conclusion: This study describes the safety profile of bupropion (Zyban) as used in the community; a small number of adverse events were reported that were not included on the SmPC. For many events, nicotine withdrawal was a confounding factor. SMR calculations did not provide evidence for a higher rate of mortality (either all-cause or condition-specific) in the PEM cohort relative to smokers from the CPS-II cohort in the USA. While reassuring, the SMR should be interpreted in context with results from other studies on bupropion when used for smoking cessation.