Varenicline

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). There have been postmarketing reports of traffic accidents, near-miss incidents in traffic, or other accidental injuries in patients taking varenicline.

Postmarketing reports of hypersensitivity reactions (including angioedema) and rare cases of serious skin reactions (including Stevens-Johnson syndrome and erythema multiforme) have been reported. Patients should be instructed to discontinue use and contact healthcare provider if signs/symptoms occur.

Dose-dependent nausea may occur; both transient and persistent nausea has been reported. Dosage reduction may be considered for intolerable nausea.

Post-marketing cases of serious neuropsychiatric events (including depression, suicidal thoughts, and suicide) have been reported in patients with or without preexisting psychiatric disease; some cases may have been complicated by symptoms of nicotine withdrawal following smoking cessation. Subsequent controlled trials in patients with or without psychiatric disorders; however, have not identified significant differences in neuropsychiatric effects for patients taking varenicline, bupropion, nicotine patches, or placebo (Anthenelli 2013; Anthenelli 2016; Gibbons 2013; Thomas 2015). Monitor all patients for behavioral changes and psychiatric symptoms (eg, agitation, depression, suicidal behavior, suicidal ideation); inform patients to discontinue treatment and contact their health care provider immediately if they experience any behavioral and/or mood changes. Of post-marketing cases, many resolved following therapy discontinuation.

Cases of somnambulism, involving harmful behavior to self, others or property, have been reported. Discontinue treatment if somnambulism occurs. Disease-related concerns:

Treatment may increase risk of cardiovascular events. A meta-analysis of 15 clinical trials, including a placebo-controlled trial in patients with stable cardiovascular disease, showed an increased incidence of major cardiovascular events (combined outcome of cardiovascular-related death, nonfatal MI, nonfatal stroke) in patients using varenicline compared with placebo. Cardiovascular events were uncommon in both the varenicline and placebo groups. These findings did not reach statistical significance, although data was consistent. Events occurred primarily in patients with known cardiovascular disease. The meta-analysis also showed a lower incidence of all-cause and cardiovascular mortality in varenicline-treated patients, although this was not statistically significant either.

Use with caution in patients with renal impairment; dosage adjustment required with severe impairment.

Seizures have been reported in patients with or without a history of seizures. Seizures generally occurred within the first month of therapy. Consider the risks against the benefits before initiating in patients with a history of seizures or other factors that can lower the seizure threshold; discontinue use if seizures occur during therapy. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.