Gastrointestinal adverse effects of varenicline at maintenance dose: a meta-analysis

BACKGROUND: Tobacco smoking remains the leading modifiable health hazard and varenicline is amongst the most popular pharmacological options for smoking cessation. The purpose of this study is to critically evaluate the extent of gastrointestinal adverse effects of varenicline when used at maintenance dose (1 mg twice a day) for smoking cessation. METHODS: We conducted a meta-analysis of randomised controlled trials published in PUBMED and EMBASE according to the PRISMA guidelines. Selected studies satisfied the following criteria: (i) duration of at least 6 weeks, (ii) titrated dose of varenicline for 7 days then a maintenance dose of 1 mg twice-per-day, (iii) randomized placebo-controlled design, (iv) extractable data on adverse event - nausea, constipation or flatulence. Data was synthesized into pooled odd ratios (OR) basing on random effects model. Quality of studies was also rated as per Cochrane risk-of-bias assessment. Number need to harm (NNH) was calculated for each adverse effect. RESULTS: 98 potentially relevant studies were identified, 12 of which met the final inclusion criteria (n = 5114). All 12 studies reported adverse events on nausea, which led to an OR of 4.45 (95% CI = 3.79-5.23, p < 0.001; I(2 )= 0.06%, CI = 0%-58.34%) and a NNH of 5. Eight studies (n = 3539) contain data on constipation pooled into an OR of 2.45 (95% CI = 1.61-3.72, p < 0.001; I(2 )= 34.09%, CI = 0%-70.81%) with a NNH of 24. Finally, five studies (n = 2516) reported adverse events of flatulence, which pooled an OR of 1.74 (95% CI = 1.23-2.48, p = 0.002; I(2 )= 0%, CI = 0%- 79.2%) with a NNH of 35. CONCLUSIONS: Use of varenicline at maintenance dose of 1 mg twice a day for longer than 6 weeks is associated with adverse gastrointestinal effects. In realistic terms, for every 5 treated subjects, there will be an event of nausea, and for every 24 and 35 treated subjects, we will expect an event of constipation and flatulence respectively. Family physicians should counsel patients of such risks accordingly during their maintenance therapy with varenicline.