Kendra BaileyAdvisor: Dr. Gurwell

Importance to Practice1.3 billion smokers world wide

20.9% in the United StatesObvious Health Risks

Leading cause of preventable deathCardiovascular Disease

70% higher chance of dying from coronary artery disease

Lung DiseaseVery difficult to quit

Up to 60% relapse within first yearDue to addictive nature of nicotine

Nicotine Replacement TherapyNicotine Patches-FDA

approved in 1991Maintain nicotine levels

lower than that achieved by smoking

Quit rates 2.8 times higher than placebo

Risk of nicotine toxicity if patient smokes while wearing the patch

Nicotine Gum-FDA approved in 1984Nicotine levels lower

than with cigarettes and patches

Poor compliance

Non-Nicotine Replacement Bupropion

Atypical anti-depressant that agonizes dopamine and adrenergic receptors and antagonizes nicotine receptors

Effective in those patients who are resistant to NRT and preferred in patients with some mental disorders

Compared to placebo (quit rate 19.05%), quit rates were: 100 mg: 28.5% 150 mg: 28.6% 300 mg : 44.2%

Total treatment time is 7-12 weeks, but can be extended up to one year

VareniclineNon-nicotine replacement therapyReceived FDA approval in 2006Discovered while attempting to develop a

transdermal patch for Alzheimer's DiseaseWas shown to have smoking cessation

properties, but was dismissed until Pfizer picked up on the research

Pharmacology of VareniclineMOA: partial nicotinic acetylcholine receptor

agonist, binding specifically to the alpha 1 beta 2 receptorStimulates dopamine release-pleasurable

effects of nicotine, decrease in withdrawalDeclined sense of satisfaction with smoking

Oral administration, essentially total bioavailabilty

Half life of 17-30 hours

DosingDays 1-3: 0.5 mg once dailyDays 4-7: 0.5 mg twice dailyWeek 2-12: 1 mg twice daily

Patient can receive an additional 12 weeks of treatment if smoking cessation not obtained or danger of relapse

Determined using Phase III trialsStudies show that as dosage increased, quit rates

increased37.3% quit rate with 1 mg once daily, and 48.0% quit

rate with 1 mg twice daily compared to placebo’s 17.1%

TolerabilitySide effects very mild and include nausea,

headache, vivid dreams, and weight gainAverage weight gain 2.37-2.89 kg in 12 weeks

Rare psychiatric side effects including mood swings, agitation, and aggression have been reportedVarenicline not advised in patients with bipolar

disorder or schizophreniaUse with caution in patients w/ renal impairmentCimetidine can cause increase in systemic

exposureDoes not effect digoxin, metformin, or warfarin.

Varenicline vs. other treatment optionsVarenicline vs. SR bupropion

Quit rates at weeks 9-12 were 44.0% for varenicline, 29.5% bupropion, and 16.6% placebo

Quit rates at weeks 24 and 52 continued to show varenicline more effective

Varenicline vs bupropion, bupropion vs NRTBupropion was found to be more effective than

NRT at the 3 month and 1 year mark.Varenicline was found to be more effective than

bupropion at the 3 month and 1 year mark.

Limitations to UsageCost!!

On average $268.80 for 84 days of treatment With counseling and other maintenance, $638.80 Bupropion $227 for 60 tablets

Although high initial cost, studies have shown varenicline to be more cost effectiveCost benefit analysis show that varenicline gave

employers $540.60 in savings compared to $269.80 by bupropion

For bupropion to be more cost effective, cost for varenicline would have to exceed $616 and quit rates would have to be less than the reported 16.9%

ConclusionsWould I use varenicline in my practice?

Yes….when appropriateThere needs to be more research!

Direct studies vs. other treatmentsRemember: The patient needs to be willing to

quit, otherwise the best drug in the world won’t work!

References Arneric SP, Holliday M, Williams M. Neuronal Nicotinic Receptors: A Perspective in Two Decades

of Drug Discovery Research. Biochemical Pharmacology. 2007 October 25; 74(8): 1092-1101. Cahill K, Stead LF, Lancaster T :Department of Primary Healthcare. Nicotine Receptor Partial

Agonists for Smoking Cessation. Cochrane Database of Systemic Reviews. 2007 January 24 . Foulds J. The Neurological Basis for Partial Agonist Treatment of Nicotine Dependence:

Varenicline. International Journal of Clinical Practice. 2006 May; 60(5): 571-561. Foulds J, Steinburg MB, Williams JM, Ziedonis DM. Developments in Pharmacotherapy for Tobacco

Dependence: Past, Present, and Future. 2006 January; 25(1): 59-71. Freedman R. Exacerbation of Schizophrenia by Varenicline. American Journal of Psychiatry. 2007

August; 164(8): 1269. Frishman WH. Smoking Cessation Pharmacology-Nicotine and Non-nicotine Preparations.

Preventive Cardiology. 2007 Spring; 10(2 Supp 1):10-22. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha-4-beta-2 nicotinic acetylcholine

receptor partial agonist, vs. placebo or sustained-released bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006 July 5: 296(1): 47-55.

Jackson KC, Nahoopii R, Said Q, Dirani R, Brixner D. An Employer-Based Cost Benefit Analysis of a Novel Pharmacotherapy Agent for Smoking Cessation. Journal of Occupational and Environmental Medicine [serial on the internet]. 2007 April [cited 2007 October30]; 49(4). Available from http://www.mdconsult.com.ezproxy.uky.edu/das/article/body/80843863-3/jorg=journal&source=MI&sp=19393825&sid=638804506/N/578545/1.html.

Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, a alpha-4-beta-2 nicotinic acetylcholine receptor partial agonist, vs. sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006 July 5; 296 (1): 56-63.

Keating GM, Siddiqui AA. Varenicline: A Review of its Uses as an Aid to Smoking Cessation Therapy. CNS Drugs. 2006; 20(1): 945-960.

References cont. Kohen I, Kremen N. Varenicline-Induced Manic Episode in a Patient with

Bipolar Disorder. American Journal of Psychiatry. 2007 August; 164(8): 1269-1270.

Leeman RF, Huffman CJ, O'Malley SS. Alcohol History and Smoking Cessation in Nicotine Replacement Therapy, Bupropion Sustained Release and Varenicline Trials: A Review. Alcohol and Alcoholism. 2007, May-June; 42(3): 196-206.

Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE. Rationale, Pharmacology and Clinical Efficacy of Partial Agonists of Alpha4Beta2 nACh Receptors for Smoking Cessation. Trends in Pharmacological Science. 2007 July; 28(7): 316-325

Tobin ML. Why Chose Varenicline (Chantix) for Smoking Cessation Treatment? Issues in Mental Health Nursing. 2007 June; 28(6): 663-667.

Tonstad S, Tønnesen P, Hajek P, Williams KE, Billing CB, Reeves KR. Effect of Maintenance Therapy With Varenicline on Smoking Cessation: a Randomized Controlled Trial. JAMA. 2006 July 5; 296(1): 64-71.

Williams KE, Reeves KR, Billing CB Jr, Pennington AM, Gong J. A Double-Blind Study Evaluating the Long-Term Safety of Varenicline for Smoking Cessation. Current Medical Research and Development. 2007 April; 23(4): 793-801.

Wu P, Wilson K, Dimoulas P, Mills EJ. Effectiveness of Smoking Cessation Therapies: A Systematic Review and Meta-analysis. BMC Public Health. 2006 December 11; 6: 300