Tolerability
Overall, varenicline was safe and well tolerated in clinical trials.
Nausea was the most commonly reported adverse event in fixed-dose, placebo-controlled studies.6 Although approximately 3% of patients stopped varenicline prematurely because of upset stomach,6 most rated their nausea as mild to moderate and reported reduced nausea with continued varenicline use. For patients with intolerable nausea, consider reducing the dosage.
Sleep disturbance, constipation, flatulence, and vomiting were twice as prevalent among the varenicline groups compared with placebo.6 Overall treatment discontinuation rates were similar with varenicline, 1 mg bid, and placebo (12% vs. 10%) in 12-week phase-2 and phase-3 clinical trials.6
To improve tolerability, the FDA recommends splitting varenicline into twice-daily doses.6,13
Dosing
Start varenicline at 0.5 mg/d for 3 days, 0.5 mg bid for the next 4 days, then 1 mg bid through week 12. To improve tolerability, advise patients to take varenicline after eating and with a full glass of water.
Setting a target quit date (TQD) is a critical element of smoking cessation treatment. Schedule the TQD for the same day the patient begins 1 mg bid varenicline dosing so that the medication is approaching maximal steady-state concentrations during the quit attempt to help counter withdrawal. Allow patients to continue smoking during the 1-week titration period, but stress the importance of trying to quit on the TQD.
Because varenicline is primarily eliminated through the kidneys, limit dosages to 0.5 mg bid in patients with severe renal impairment (estimated creatinine clearance 6,13
Varenicline has not been studied in patients with substance use and other psychiatric disorders—patients who account for most of a psychiatrist’s caseload and whose nicotine dependence is difficult to treat. Even so, the medication’s lack of discernible drug-drug interactions and selectivity of α4β2 nAChR action make varenicline worth considering for these patients.
Varenicline also has not been tested or approved for use in adolescent or pregnant smokers; research is needed on how the medication works in these patients.
Role of behavioral treatment
The Clinical Practice Guideline, Treating Tobacco Use and Dependence12 suggests combining antismoking pharmacotherapy with counseling to maximize outcome. To that end, varenicline’s manufacturer has developed a personalized behavioral support program for patients taking the medication.14 Adjunctive therapy via the Internet, telephone, or direct mail can complement other extra-treatment supports—such as toll-free quit lines and classes offered through health organizations—and more-formal, intensive behavioral interventions.
Related resources
- Varenicline Web site. www.chantix.com.
- World Health Organization. Causes of death. In: Epidemiology and burden of disease. Geneva: World Health Organization, 2003.
- Fiore MC, Bailey WC, Cohen SJ, et al. Clinical practice guideline. Treating tobacco use and dependence. Rockville, MD: U.S. Department of Health and Human Services, 2000. www.surgeongeneral.gov/tobacco/treating_tobacco_use.pdf.
Drug brand names
- Bupropion SR • Wellbutrin, Zyban
- Varenicline • Chantix
Disclosures
Dr. Anthenelli is a consultant for Alkermes and Cephalon and a speaker and consultant for Pfizer and sanofi-aventis.
The Tri-State Tobacco and Alcohol Research Center receives research grants from Addex, Ortho-McNeil Neurologics, and sanofi-aventis.
Dr. Anthenelli and the Tri-State Tobacco and Alcohol Research Center were members of the Varenicline Study Group.
Acknowledgments
The writing of this article was supported in part by National Institutes of Health Grant Awards Nos. AA013957 and AA013307.
The author thanks Reene Cantwell for her technical assistance in preparing this article.