The clinical practice guidelines of the U.S. Public Health Service have identified pharmacologic agents as either first-line or second-line treatment for tobacco use and dependence and as aids to smoking cessation.23
Since 2000, options for first-line pharmacotherapy have included nicotine-replacement therapy and sustained-release bupropion, with the addition of varenicline as a first-line agent in the 2008 guidelines.23
All first-line medications are approved by the Food and Drug Administration (FDA) for assistance with smoking cessation.
Varenicline can be chosen as a treatment for patients who have never received pharmacologic treatment for smoking cessation as well as for those in whom other treatments have not been successful. Candidates for treatment should show some evidence of motivation to quit smoking. Varenicline is contraindicated for use during pregnancy and lactation until evidence of its safety in pregnant and nursing women is available.
Clinicians prescribing varenicline should be mindful that treatment results in real-world clinical settings are likely not to be as good as those reported in the published clinical trials for two main reasons. First, the degree of behavioral support provided in the published studies is difficult to replicate in practice. Second, the subjects selected for inclusion in clinical trials are generally healthy and may not be representative of typical clinical populations.
For smokers starting varenicline therapy, a target quitting date should be set for 1 week after the initiation of treatment. Varenicline treatment should be initiated with a 1-week dose-adjustment period, with a dose of 0.5 mg once daily on days 1 through 3, 0.5 mg twice daily on days 4 through 7, and the target dose of 1.0 mg twice daily starting on day 8 (i.e., the target quitting date). The 1-week dose-adjustment period reduces nausea as compared with initial therapy at 1 mg twice daily.17
Patients should be advised to take each dose with food in order to reduce the risk of nausea. For problematic nausea, the dose may be reduced to 1 mg once daily. If nausea resolves at the lower dose, another attempt to increase the dose to the target of 1 mg twice daily is appropriate.
Since more than 80% of varenicline is excreted unchanged in the urine,24
no dose adjustments are required for hepatic impairment. In patients with severe renal impairment (estimated creatinine clearance, <30 ml per minute), a reduction in the dose to 0.5 mg daily is recommended. Varenicline is effectively removed with hemodialysis and may be used at a similar dose in patients undergoing thrice-weekly hemodialysis. Dose adjustments are not indicated in elderly patients, and no adjustments are required in patients with other coexisting medical illnesses. Because varenicline is minimally metabolized, no clinically meaningful drug–drug interactions have been described.
No special clinical laboratory monitoring is required for patients taking varenicline. Use of the drug has not been associated with any clinically important metabolic, hematologic, or electrocardiographic abnormalities (e.g., liver-test abnormalities, reductions in blood counts, or prolongation of the QT interval, respectively).
Continued therapy with varenicline may be indicated in smokers who have been unable to abstain from smoking after reaching the target quitting date and who are still motivated to quit. Evidence from clinical trials suggests a progressive increase in the 7-day point-prevalence rate of abstinence throughout 6 to 8 weeks of treatment.14,15
In patients who are unable to completely abstain from smoking and are not motivated to continue with a quitting plan, discontinuation of therapy is indicated before completion of a 12-week course. Therapy may be discontinued abruptly after 12 to 24 weeks, with no tapering required.
The average retail cost of varenicline at a dose of 1 mg twice daily is $3 to $4 per day. As with other medication, the retail cost may vary widely. Coverage by pharmacy plans and medical assistance plans is not uniform among states or regions.
Pharmacotherapy for smoking cessation is most effective with brief counseling at the initiation of treatment and periodically during follow-up. The U.S. Preventive Services Task Force has concluded that even “minimal counseling, lasting less than 3 minutes, has been shown to increase overall tobacco abstinence rates” and that “increasing session length and frequency increased efficacy in a dose–response manner.”25
Counseling by telephone may also be provided as an adjunct to pharmacotherapy.26