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Pfizer Inc's Chantix (varenicline tartrate), approved by the FDA in May 2006, helps cigarette smokers to quit smoking.1
Varenicline is a nonnicotinic drug with a dual mechanism of action (agonist and antagonistic activity). Normally, nicotine binds to the a4b2 neuronal nicotinic acetylcholine receptor subunit, which stimulates the central nervous mesolimbic dopamine system, the mechanism responsible for the reinforcement and reward experience associated with smoking.2 Varenicline, a partial agonist, has an affinity for the a4b2 subunit, stimulating receptor-mediated activity at a lower level than nicotine (agonistic activity). By binding to the a4b2 subunit, varenicline blocks nicotine binding, preventing stimulation of the central nervous mesolimbic dopamine system (antagonistic activity).2
About 92% of the drug is excreted unchanged in urine and primarily eliminated via glomerular filtration with active tubular secretion via the organic cation transporter.2 Dose adjustment is not necessary for mild renal impairment (creatinine clearance of ≥50 mL/min and ≤80 mL/min). There is a 1.5-and 2.1-fold increase in varenicline exposure in patients with moderate (≥30 mL/min and ≤50 mL/min) and severe creatinine clearance (≤30 mL/min), respectively. Varenicline undergoes minimal hepatic metabolism.2
The efficacy of Chantix was confirmed in 6 clinical studies all enrolling chronic cigarette smokers (10 cigarettes/ day). Abstinence from smoking was verified by patient self-report and measurement of exhaled carbon monoxide (CO; ≤10 ppm) at weekly visits.3
Two identical trials, both phase 3, double-blind, placebo-and active-controlled, parallel-group, multicenter studies randomized patients to receive Chantix, bupropion SR, or placebo.2,3 Patients who had used bupropion SR previously were excluded. Chantix was titrated according to the following schedule: 0.5 mg qd for 3 days; 0.5 mg bid daily for 4 days; then 1 mg bid. Titration of bupropion SR was 150 mg daily for 3 days, then 150 mg twice daily.
Patients were treated for 12 weeks total, including titration phase, and followed for 40 weeks posttreatment. A total of 2045 patients were enrolled in both studies (n = 1022 and n = 1023).4,5
In both studies, Chantix-treated patients had a higher superiority rate. In one study, Chantix had a CO-confirmed abstinence rate of 44% during weeks 9 through 12, compared with the other 2 arms (bupropion SR = 30%; placebo = 17%). Also, the Chantix group had a higher rate (29%) of being continuously abstinent from 1 week after the target quit date (TQD) to the end of treatment (EOT), compared with bupropion SR (23%) and placebo (12%).4,5 The second study also showed similar results where Chantix-treated patients had a higher superiority rate of CO-confirmed abstinence during weeks 9 through 12 (varenicline = 44%; bupropion SR = 30%; placebo = 18%). Continuous abstinent percentage from 1 week after TQD through the EOT was also similar to the first study (Chantix = 29%; bupropion = 21%; placebo = 11%).2
A study designed to assess longterm abstinence with Chantix therapy versus placebo demonstrated Chantix superiority rate in maintaining smoking cessation. Patients received open-label Chantix 1 mg bid for 12 weeks, then were randomized to active or placebo for the next 12 weeks.2,3 The Chantix group had a higher continuous abstinence rate (70%) versus placebo (50%). During posttreatment follow-up, superiority of Chantix (54%) was maintained, compared with placebo (39%).2,3
Most frequently reported side effects of Chantix were nausea, insomnia, abnormal dreams, headache, dyspepsia, constipation, and flatulence.2 The incidence of nausea was dose-related and categorized as mild to moderate. If nausea is intolerable, a lower dose should be considered.3
Patients should be advised to set a TQD, and treatment should begin 1 week prior to that date. Dose should be titrated to 1 mg bid following a titration schedule of 0.5 mg qd for 3 days; 0.5 mg bid on days 4-7.2 Chantix should be taken after a meal with a full glass of water. Chantix treatment should be supported with counseling and educational materials on smoking cessation.2
Manufacturer recommendation for storage is at room temperature up to 77°F. Each strength, 0.5 and 1 mg, is available in cards and in bulk bottles of 56 tablets.2 Chantix is classified as in pregnancy category C and is not recommended for use in children under the age of 18.
Ms. Domenici and Dr. Patel are both pharmacists at Brigham and Women's Hospital, Boston, Mass.
1. The FDA Approves New Drug for Smoking Cessation. FDA Consumer magazine. July-August 2006. Available at: www.fda.gov/fdac/features/2006/406_smoking.html. Accessed January 8, 2007.
2. Chantix [package insert]. New York, NY: Pfizer Inc; 2006.
3. Pfizer "Dear Healthcare Professional Letter" (overall safety and efficacy). January 10, 2007.