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

To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies.

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.

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.

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.

Clinicaltrials.gov Identifier: NCT01456936.