Chantix (varenicline)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved May 2006

Specific Treatments:

Smoking Cessation

Therapeutic Areas

General Information

Chantix (varenicline) is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain.

Chantix is specifically indicated for use as an aid in smoking cessation.

Chantix is supplied as a capsule for oral administration. The recommended initial regimen utilizes a 1-week dosing titration: 0.5 mg once daily on days 1-3, and 0.5 mg twice daily on days 4-7, followed by 1 mg twice daily for 12 weeks, with responders receiving an additional 12-week treatment course to promote long-term abstinence.

Clinical Results

FDA Approval
Approval of Chantix was based on six clinical trials, which enrolled a combined 3659 chronic smokers (at least 10 cigarettes per day).

Study 1
This dose-ranging placebo-controlled phase II study was designed to investigate the optimum treatment regimen for the drug. Data from the study indicated that total doses of 1 mg or 2 mg daily both promoted successful smoking cessation.

Study 2
This placebo controlled study enrolled 627 patients, who received 0.5 mg or 1 mg Chantix or placebo twice daily for 12 weeks (both with and without initial 1-week dose titration), with subsequent 40 week observational follow-up. Trial data indicated that 45% of subjects in the low-dose group and 51% in the high dose group had CO-confirmed continuous abstinence from weeks 9 to 12, vs. 12% for placebo. Further, 31% of subjects in each group achieved continuous abstinence from 1 week after the initiation of dosing through the end of treatment, vs. 8% for placebo.

Study 3
This placebo-controlled flexible dosing study enrolled 312 subjects, to investigate the effects of a patient-directed dosing strategy. Subjects received an initial regimen of 0.5 mg twice daily, followed by a patient-adjusted schedule of 0.5 mg once or twice daily (freely adjusted). 69% of subjects titrated to the higher dose at some point during the study; the higher dose was modal for 44% of subjects. 40% of subjects had CO-confirmed continuous abstinence for weeks 9-12, vs. 15% for placebo, and 29% maintained continuous abstinence from the 2 weeks after treatment initiation through the end of treatment, vs. 9% for placebo.

Studies 4 & 5
These identical, active- and placebo-controlled studies enrolled 1022 (Study 4) and 1023 (Study 5) subjects, who received 1 mg Chantix twice daily, 150 mg of the approved smoking cessation aid bupropion sustained-release twice daily, or placebo, for 12 weeks, with subsequent 40 week observational follow-up. In Study 4, subjects receiving Chantix achieved superior CO-confirmed smoking abstinence for weeks 9 through 12 (44%), vs. either bupropion (30%) or placebo (17%). Smoking-abstinence rate for bupropion was superior to placebo. 29% of subjects receiving Chantix were continuously smoking-abstinent from week 2 through the end of treatment, vs. 23% for bupropion and 12% for placebo. In Study 5, superior abstinence for weeks 9-12 was achieved with Chantix (44%), vs. 30% for bupropion and 18% for placebo (bupropion was again superior to placebo). 29% of Chantix subjects maintained abstinence for week 2 through the end of treatment, vs. 21% for bupropion and 11% for placebo.

Long-Term Follow-up
Studies 1-5 all included 40 week follow-up periods, which investigated long-term abstinence rates following a course of treatment. For all studies, subjects receiving Chantix were more likely to maintain abstinence than subjects receiving placebo (Study 2: 19% low dose, 23% high dose, vs. 4% placebo; Study 3: 22% flex. dose, vs. 8% placebo; Study 4: 21% high dose, 16% bupropion, vs. 8% placebo; Study 5: 22% high dose, 14% bupropion, vs. 10% placebo). Abstinence rates were not significantly different for Chantix and bupropion.

Study 6
This open label study enrolled 1927 chronic smokers, and was designed to investigate the efficacy of the drug on promoting long-term smoking abstinence. Subjects received 1 mg Chantix twice daily for 12 weeks in a run-in period; subjects achiving abstinence at the end of this regimen were randomized to a double-blind regimens of either continued Chantix therapy (1 mg twice daily) or placebo for an additional 12 weeks, with subsequent 28 week follow-up. Trial data indicated that continuous abstinence for weeks 13 through 24 was higher for subjects receiving continued Chantix therapy (70%) than for placebo (50%); this superiority was maintained through 28 weeks post treatment (54% vs. 39%).

Ongoing Study Commitments

  • Pfizer comits to conduct a study to determine the multiple-dose pharmacokinetics of varenicline in pediatric patients in order to determine the appropriate doses for efficacy and safety evaluations in adolescent smokers, ages 12 through 16, inclusive, to determine the adverse event profile in adolescent patients, and to establish whether there is any age group (or weight group) for whom varenicline is so poorly tolerated that its utility as an aid to smoking cessation treatment should not be evaluated in that group.
    Final Report Submission: by November 10, 2007
  • Pfizer commits to conduct a study to determine whether varenicline, as part of an overall smoking cessation program, is effective in achieving and maintaining smoking cessation in tobacco-addicted adolescents, ages 12 through 16, inclusive, to determine a safe and effective dose, and to document the ability of treating physicians to select appropriate patients. You will need to develop a means for determining reliable criteria for appropriate patient selection of tobacco-addicted teens so that teenage smokers who are not addicted will not be recruited, and so that labeling can convey these criteria to physicians who may wish to use the drug in adolescents.
    Final Report Submission: by May 10, 2011
  • Pfizer commits to conduct a prospective epidemiologic cohort study in pregnant women who are smokers and who are exposed to varenicline at the time of conception or any time during pregnancy. This information will be used to assess the potential risk to the fetus and/or live born infant.
    Protocol Submission: by November 10, 2006
    Study Start: by May 10, 2007
    Final Report Submission: by May 10, 2011

Side Effects

Adverse events associated with the use of Chantix may include, but are not limited to, the following:

  • Nausea
  • Insomnia
  • Headache
  • Abnormal Dreams
  • Abdominal Pain
  • Fatigue/Malaise/Asthenia
  • Upper Respiratory Tract Disorder
  • Flatulence
  • Dry Mouth

Mechanism of Action

Chantix is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms.

Literature References

Foulds J The neurobiological basis for partial agonist treatment of nicotine dependence: varenicline International Journal of Clinical Practice 2006 May;60(5):571-6

Neuropharmacology and potential efficacy of new treatments for tobacco dependence. Expert Opinion on Investigational Drugs 2006 Feb;15(2):107-16

Obach RS, Reed-Hagen AE, Krueger SS, Obach BJ, O'Connell TN, Zandi KS, Miller S, Coe JW Metabolism and disposition of varenicline, a selective alpha4beta2 acetylcholine receptor partial agonist, in vivo and in vitro. Drug Metabolism and Disposition 2006 Jan;34(1):121-30. Epub 2005 Oct 12

Coe JW, Brooks PR, Vetelino MG, Wirtz MC, Arnold EP, Huang J, Sands SB, Davis TI, Lebel LA, Fox CB, Shrikhande A, Heym JH, Schaeffer E, Rollema H, Lu Y, Mansbach RS, Chambers LK, Rovetti CC, Schulz DW, Tingley FD 3rd, O'Neill BT Varenicline: an alpha4beta2 nicotinic receptor partial agonist for smoking cessation Journal of Medicinal Chemistry 2005 May 19;48(10):3474-7

Additional Information

For additional information regarding Chantix or Smoking Cessation, please visit the Chantix web page.


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