Nausea during the first few weeks of varenicline therapy may reduce adherence, a study from North America has found.

The authors analysed data on 870 adults receiving varenicline in two smoking cessation trials conducted at multiple sites in Canada and the United States. A total of 449 were taking part in the Quit2Live and 421 in the Pharmacogenetics of Nicotine Addiction Treatment (PNAT) trial. Information on nausea severity was self-reported and adherence to treatment was assessed by measuring plasma or salivary varenicline concentration. Smoking abstinence was confirmed with either cotinine or carbon monoxide testing at a range of study time points.

At week 12, of the 381 participants for whom full data were available in Quit2Live, 108 had stopped smoking and 273 were still smoking. Respective values for PNAT were 144 (of 376) and 232.

Early nausea was indirectly associated with lower cessation rates at multiple time points in Quit2Live; odds ratios (OR) ranging from 0.92 (95% CI: 0.83-0.99) to 0.94 (95% CI: 0.86–0.99). This relationship was associated with reduced varenicline adherence (assessed by plasma varenicline levels).

The relationship between nausea, adherence and cessation was similar in direction but weaker in effect size; ORs ranging from 0.98 (95% CI: 0.90-1.01) to 0.99 (95% CI: 0.95-1.03) in PNAT, where adherence was assessed using salivary varenicline levels.

Varenicline has been shown to be an effective pharmacotherapy in helping smokers achieve long-term cessation, significantly increasing stop rates compared with placebo. However up to half of smokers treated with varenicline fail to achieve abstinence,¹ and reduced medication adherence may be one factor contributing to failure to quit.

Previous studies have shown that a third of varenicline-treated smokers were non-adherent by the second treatment week (one week post-dose titration),¹ and non-adherent smokers are significantly less likely to be abstinent at a range of treatment time points. In surveys investigating discontinuation of, and non-adherence with, varenicline the most frequently cited reason was adverse events, the most common being nausea.¹ Nausea in varenicline treated patients is generally mild to moderate, starting in the first 2 weeks of treatment and diminishing over the course of treatment.

The authors say that better management of early nausea during varenicline treatment may improve smoking cessation success rates by increasing varenicline adherence. They suggest extending the varenicline titration period and/or allowing patients to control the rate of titration and using lower dose regimens (0.5 mg twice daily). Explaining to patients that nausea may occur in the early treatment stages, and that the effect lessens over time, and providing antiemetic medication during early treatment may also help improve adherence, they say.

Dr Jez Thompson