- First Online:
Varenicline is an orally administered small molecule with partial agonist activity at the α4β2 nicotinic acetylcholine receptor. Varenicline was approved by both the US FDA and the European Medicines Agency of the EU in 2006 as an aid to smoking cessation. Subsequently, varenicline has been approved in over 80 other countries.
Varenicline is almost entirely absorbed following oral administration, and absorption is unaffected by food, smoking or the time of day. Varenicline undergoes only minimal metabolism and approximately 90% of the drug is excreted in the urine unchanged. Varenicline has a mean elimination half-life after repeated administration of approximately 24 hours in smokers. The area under the plasma concentration-time curve is increased in patients with moderate or severe renal failure. No clinically relevant varenicline-drug interactions have been identified.
In two identical, randomized, double-blind, phase III clinical trials in healthy, motivated-to-quit, mainly Caucasian smokers aged 18–75 years in the US, 12 weeks of treatment with varenicline 1 mg twice daily was associated with significantly higher abstinence rates over weeks 9–12 than sustained-release bupropion 150 mg twice daily or placebo. In a separate phase III trial, an additional 12 weeks of treatment in smokers achieving abstinence in the first 12 weeks was associated with greater abstinence through to week 52 than placebo treatment. Varenicline treatment was also associated with significantly higher rates of abstinence than placebo treatment in randomized, double-blind, clinical trials in smokers in China, Japan, Korea, Singapore, Taiwan and Thailand. In a randomized, open-label, multi-national, phase III trial, varenicline treatment was associated with a significantly higher rate of abstinence than transdermal nicotine-replacement therapy. In these trials, varenicline treatment was associated with lower urge to smoke and satisfaction from smoking in relapsers than placebo or active comparators.
In the two US phase III trials, 12 weeks of treatment with varenicline 1 mg twice daily had an acceptable safety and tolerability profile. Nausea and abnormal dreams were the most common adverse events that occurred in more varenicline than placebo recipients. The incidence and prevalence of nausea were greatest in weeks 1 and 2 of treatment, and declined thereafter. The prevalence of early adverse effects can be reduced by individual dose titration. Adverse events associated with varenicline therapy have been reported in post-marketing surveillance, including neuropsychiatric events such as depressed mood, agitation, changes in behaviour, suicidal ideation and suicide. Currently, it is unclear whether the association of varenicline therapy with these adverse events is causal, coincidental or related to smoking cessation.
Given the greater efficacy of varenicline compared with other pharmacotherapies, and the high risk of morbidity and mortality associated with continued smoking, varenicline is a valuable pharmacological aid to smoking cessation.
- 5.Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev 2007 Jan 24; (1): CD000031Google Scholar
- 6.Stead L, Perera R, Bullen C, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev 2008 Jan 23; (1): CD000146Google Scholar
- 7.Cahill K, Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2007 Jan 24; (1): CD006103Google Scholar
- 8.US Department of Health and Human Services. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Rockville (MD): US Department of Health and Human Services, 1988Google Scholar
- 19.Pfizer Inc. Chantix (varenicline tartrate) US prescribing information [online]. Available from URL: http://www.chantix.com/content/Prescribing_Information.jsp [Accessed 2008 Nov 4]
- 25.Xiao Y, Lv Y, Zhang X, et al. The pharmacokinetic and tolerability profile of varenicline in healthy Chinese volunteers. Int J Clin Pharmacol 2009 Apr; 47(4): 246–54Google Scholar
- 26.Pfizer Inc. Chantix (varenicline tartrate) European prescribing information [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/champix/H-699-PI-en.pdf [Accessed 2008 Nov 4]
- 32.Nides M, Oncken C, Gonzales D, et al. Smoking cessation with varenicline, a selective α4β2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Arch Intern Med 2006 Aug 14–28; 166(15): 1561–8PubMedCrossRefGoogle Scholar
- 35.Nakamura M, Oshima A, Fujimoto Y, et al. Efficacy and tolerability of varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, in a 12-week, randomized, placebo-controlled, dose-response study with 40-week follow-up for smoking cessation in Japanese smokers. Clin Ther 2007 Jun; 29(6): 1040–56PubMedCrossRefGoogle Scholar
- 50.Parsons AC, Shraim M, Inglis J, et al. Interventions for preventing weight gain after smoking cessation. Cochrane Database Syst Rev (Online) 2009; (1): CD006219Google Scholar
- 51.US Food and Drug Administration. Information for healthcare professionals: Varenicline (marketed as Chantix) [online]. Available from URL: http://www.fda.gov/cder/drug/InfoSheets/HCP/vareniclineHCP.htm [Accessed 2008 Nov 4]
- 53.Pfizer Inc. Medication guide Chantix® (varenicline) tablets [online]. Available from URL: http://www.pfizer.com/files/products/ppi_chantix.pdf [Accessed 2009 Mar 26]
- 54.Tonstad S, Davies S, Flammer M, et al. Incidence of depression in randomized, double-blind, placebo-controlled varenicline clinical trials [abstract]. 10th Annual Conference of SRNT Europe; 2008 Sep 23–26; Rome. Available from URL: http://www.srnt.org/meeting/europdf/AbstractBookSRNTEurope2008.pdf [Accessed 2009 May 28]
- 55.Russ C, Davies S, Flammer M, et al. Incidence of psychiatric adverse events other than depression in randomized, double-blind, placebo-controlled varenicline clinical trials. 10th Annual Conference of SRNT Europe; 2008 Sep 23–26; Rome. Available from URL: http://www.srnt.org/meeting/europdf/AbstractBookSRNTEurope2008.pdf [Accessed 2009 May 28]
- 65.Moore TJ, Cohen MR, Furberg CD. Strong safety signal seen for new varenicline risks [online]. Available from URL: http://www.ismp.org/docs/vareniclineStudy.asp [Accessed 2008 Nov 4]
- 66.Hauben M, Wilson G, Reich L. A preliminary quantitative analysis of the spontaneous reporting of selected adverse events with chantix in the US FDA adverse event reporting system data base [abstract]. 10th Annual Conference of SRNT Europe; 2008 Sep 23–26; Rome. Available from URL: http://www.srnt.org/meeting/europdf/AbstractBookSRNTEurope2008.pdf [Accessed 2009 May 28]
- 67.American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1995Google Scholar