Transcript Document 7883247

Kendra Bailey
Advisor: Dr. Gurwell
Importance to Practice
 1.3 billion smokers world wide
 20.9% in the United States
 Obvious Health Risks
 Leading cause of preventable death
 Cardiovascular Disease

70% higher chance of dying from coronary artery disease
 Lung Disease
 Very difficult to quit
 Up to 60% relapse within first year
 Due to addictive nature of nicotine
Nicotine Replacement Therapy
 Nicotine Patches-FDA
approved in 1991
 Maintain 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 1984
 Nicotine 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:
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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
Varenicline
 Non-nicotine replacement therapy
 Received FDA approval in 2006
 Discovered while attempting to develop a transdermal
patch for Alzheimer's Disease
 Was shown to have smoking cessation properties, but
was dismissed until Pfizer picked up on the research
Pharmacology of Varenicline
 MOA: partial nicotinic acetylcholine receptor agonist,
binding specifically to the alpha 1 beta 2 receptor
 Stimulates dopamine release-pleasurable effects of
nicotine, decrease in withdrawal
 Declined sense of satisfaction with smoking
 Oral administration, essentially total bioavailabilty
 Half life of 17-30 hours
Dosing
 Days 1-3: 0.5 mg once daily
 Days 4-7: 0.5 mg twice daily
 Week 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 trials
 Studies show that as dosage increased, quit rates
increased
 37.3% quit rate with 1 mg once daily, and 48.0% quit rate
with 1 mg twice daily compared to placebo’s 17.1%
Tolerability
 Side effects very mild and include nausea, headache,
vivid dreams, and weight gain
 Average weight gain 2.37-2.89 kg in 12 weeks
 Rare psychiatric side effects including mood swings,
agitation, and aggression have been reported
 Varenicline not advised in patients with bipolar disorder
or schizophrenia
 Use with caution in patients w/ renal impairment
 Cimetidine can cause increase in systemic exposure
 Does not effect digoxin, metformin, or warfarin.
Varenicline vs. other treatment
options
 Varenicline 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 NRT
 Bupropion 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 Usage
 Cost!!
 On average $268.80 for 84 days of treatment

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With counseling and other maintenance, $638.80
Bupropion $227 for 60 tablets
 Although high initial cost, studies have shown varenicline
to be more cost effective
 Cost 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%
Conclusions
 Would I use varenicline in my practice?
 Yes….when appropriate
 There needs to be more research!
 Direct studies vs. other treatments
 Remember: The patient needs to be willing to quit,
otherwise the best drug in the world won’t work!
References
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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):
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Frishman WH. Smoking Cessation Pharmacology-Nicotine and Non-nicotine Preparations. Preventive Cardiology.
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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:
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Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, a alpha-4-beta-2 nicotinic acetylcholine receptor partial
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Keating GM, Siddiqui AA. Varenicline: A Review of its Uses as an Aid to Smoking Cessation Therapy. CNS Drugs.
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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