Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial

Objective: To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies. Methods: This was a multinational, multicenter, post hoc analysis of frequently reported treatment-emergent AEs from a large, phase 4, double-blind, randomized, triple-dummy, placebo-controlled trial (EAGLES), conducted between November 30, 2011, and January 13, 2015, that included smokers with and without psychiatric disorders (N=8144). Treatments were varenicline 1 mg twice daily, bupropion sustained-release 150 mg twice daily, and nicotine patch 21 mg once daily with tapering (12-week treatment, 12-week nontreatment follow-up), with incidence, time to onset, and duration of frequently reported AEs (≥5% of participants in any treatment group) measured. Risk differences for AEs for varenicline and bupropion vs nicotine patch were compared. Results: Across frequently reported AEs, nausea, insomnia, abnormal dreams, anxiety, irritability, dry mouth, fatigue, and application site pruritus differed significantly in active treatment vs placebo groups. Risk differences were as follows: for nausea with varenicline vs nicotine patch, 15.50% (95% CI, 13.20% to 17.80%); for insomnia with bupropion vs nicotine patch, 2.58% (CI, 0.65% to 4.51%); and for abnormal dreams with varenicline and bupropion vs nicotine patch, –2.49% (CI, –4.35% to –0.64%) and –5.60% (CI, –7.27% to –3.93%), respectively. Frequently reported AEs of severe intensity and treatment discontinuation were experienced by less than 1.5% and less than 3% of participants across all groups, respectively. Conclusion: Active treatments were well tolerated with comparable AE profiles. Most AEs are not clinically important, and prescribers can reassure patients that those experienced will be manageable. Trial Registration: Clinicaltrials.gov Identifier: NCT01456936.