Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study.

BACKGROUND: Varenicline tartrate (Champix), a new smoking cessation medicine, was launched in the UK in December 2006. Varenicline is a highly selective partial agonist of the alpha(4)beta(2) nicotinic acetylcholine receptor (alpha(4)beta(2) receptor). The partial agonistic binding leads to alleviation of symptoms of craving and withdrawal, and simultaneously prevents nicotine from binding to the alpha(4)beta(2) receptor thereby causing reduction in the rewarding and reinforcing effects of smoking. Regulatory concerns have arisen about psychiatric events associated with varenicline, including depression, suicidal ideation and changes in behaviour/emotion. AIM: To present the interim results of an ongoing study by the Drug Safety Research Unit (DSRU) monitoring the safety of varenicline.
METHODS: The observational cohort study is being conducted to study the postmarketing safety of varenicline, using modified prescription-event monitoring (PEM) methodology. Patients are identified from dispensed prescriptions issued by general practitioners (GPs) from December 2006. Demographic, clinical event (during the course and 1 month after stopping varenicline, reasons for discontinuing and suspected adverse drug reactions [ADRs] to varenicline) and drug utilization data are collected from detailed study-specific questionnaires posted to GPs at least 4 months after the date of first prescription for each patient. Event incidence densities (IDs; number of first reports of an event/1000 patient-months of exposure) are calculated.
RESULTS: The interim cohort comprises 2,682 patients: median age 47 years (interquartile range [IQR] 38-56), 60.7% females (n = 1627). Nausea/vomiting was the most frequent clinical reason for stopping varenicline (n = 91; 35.3% of clinical reasons) and the most frequently reported suspected ADR to varenicline (n = 60, 50.9% of patients for whom an ADR was reported). The most frequently reported psychiatric events (causality not implied) during treatment included (n; % of cohort): sleep disorder (43; 1.6%), anxiety (33; 1.2%), depression (29; 1.1%), abnormal dreams (26; 1.0%) and mood change (17; 0.6%). Two cases of attempted suicide were reported during treatment with varenicline (one patient took an overdose of a benzodiazepine with alcohol, the other slashed their wrist). Both these patients had previous history of psychiatric illness and precipitating factors for the event.
CONCLUSION: This study reflects 'real life' use of varenicline. Nausea/vomiting - the event most frequently reported as an ADR and as reason for stopping treatment - is listed in the UK Summary of Product Characteristics (SPC). The most frequently reported psychiatric events are listed in the UK SPC. All patients with suicidal events either had a past medical history of psychiatric illness prior to starting varenicline and/or a precipitating factor for the event. Clinicians should closely monitor patients with pre-existing psychiatric illness who are taking varenicline. Further evaluation of events of interest including psychiatric events is ongoing. Results presented are expected to change as the cohort size increases. Results of this study should be taken into account together with other clinical and pharmacoepidemiological studies.