Table 4. Nicotine Patches continued...
Most studies included healthy smokers, i.e., those without significant comorbidities such as cardiovascular disease or psychiatric disease. One study evaluated varenicline in patients with chronic obstructive pulmonary disease, and another study focused on patients with stable cardiovascular disease. However, no studies have evaluated varenicline use in cancer populations.
More than 3,000 patients in clinical trials have received varenicline 1 mg twice a day for 12 to 24 weeks. The side effect profile across these 12 studies [2,4,5,6,7,8,9,10,11,12,13,14] was very consistent (although incidence varied) and comprised the following:
- Nausea (13%–52%).
- Insomnia (10%–35%).
- Headache (8%–24%).
- Abnormal dreams (6%–22%).
- Dyspepsia (6%–13%).
- Constipation (7%–12%).
- Flatulence (6%–12%).
- Fatigue or somnolence (6%–10%).
Cardiovascular events often occurred as frequently in the placebo and nicotine replacement arms as in the varenicline arm and overall were rare.
Only one study evaluated varenicline in patients with stable cardiovascular disease. At week 24, this study demonstrated 7-day abstinence rates of 34.9% for varenicline versus 15.9% for placebo (P < .0001); at week 52, these rates were 27.9% for varenicline and 15.9% for placebo (P = .0001). The prevalence of any adjudicated cardiovascular event was 7.1% in the varenicline arm and 5.7% in the placebo arm, for a difference of 1.4%.
The dose-finding trial and package insert provide evidence that the incidence of adverse events is somewhat dose dependent.[10,15] It is not known, however, whether cardiovascular risks—in particular, in patients with cardiac comorbidities—are dose related because the study that evaluated varenicline in patients with stable cardiovascular disease studied varenicline at only the dose of 1 mg twice a day. This is an area in need of investigation.
In June 2011, the FDA updated the prescribing information label for varenicline to warn that the drug may increase the risk of cardiovascular adverse events in patients who have cardiovascular disease. In December 2012, the FDA updated the drug safety information for varenicline to include the results of a large meta-analysis that evaluated cardiovascular adverse events in patients who received either varenicline or placebo. Although a higher occurrence of adverse cardiovascular events that was not statistically significant was reported, there was an increased risk in patients using varenicline over those treated with placebo.