1. Varenicline (Chantix) in Smoking Cessation
Kendra Bailey
Advisor: Dr. Gurwell

2. 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
It is estimated that by 2015, 10% of deaths will be due to smoking.
You can also increase your lifespan by 7-8 years by quitting.
Nicotine has an affinity for many subtypes of neuronal nicotinic acetylcholine receptors located in the brain where is exhibits agonist effects and once these receptors are activated, dopamine is rapidly released and this elicits a pleasurable effect on the smoker which reinforces the addictive behavior (Rollema, 2007). This is the same modality used in other forms of substance abuse (Rollema, 2007) When the smoker attempts to quit, they experience withdrawal symptoms such as irritability, nausea, and headache, as well as the absence of the internal pleasure they received from smoking (Rollema, 2007).

3. 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
Patients need to be instructed on the proper way to chew the gum to avoid jaw soreness and GI effects caused by chewing too fast. Patients also don’t like that they have to avoid carbonated beverages for 15 minutes after chewing.

4. 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
Bupropion was discovered by coincidence when providers noticed that their smoking patients that they were treating for depression had decreased rates of smoking.
Bupropion was shown to be more effective if it was paired w/ a NRT such as a patch. However, this can cause compliance issues in patients and could also cause a financial burden.

5. 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

6. 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 hours
Only approximately 10% is metabolized by the liver.

7. 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%
If a patient relapses, studies show that it is best to talk to the patient and try to find a trigger for the relapse and address it to try to find a better coping mechanism or a way to avoid the trigger.
Studies have shown that patients on varenicline have a later relapse date than those on placebo with days 198 for varenicline and 87 w/ placebo.

8. Tolerability
Side effects very mild and include nausea, headache, vivid dreams, and weight gain
Average weight gain 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.
There was a case w/ a previously well controlled bipolar patient was given varenicline to replace their NRT and they experienced a manic episode one week later and the episode attributed to the dopamine release caused by the varenicline. In another incident, a well managed schizophrenic experienced psychosis after started varenicline and this was believed to be due to an increase in dopamine and norepinephrine caused by the drug. In these cases, a NRT or bupropion are more appropriate means of treatment.
In the renally impared, serum concentrations can have a 2.7 fold increase.
Patients that are diabetic and in HF would greatly benefit from this drug b/c they definitely do not need to smoke and this will not interfere w/ some common medications.

9. 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.
There haven’t been many direct studies comparing varenicline to other smoking cessation medications. This study consisted of patients w/ a mean age of and they had smoked for years. 80% had prior quit attempts. Another study using a similar patient population and methodology showed results w/ practically identical quit rates.
Since bupropion was show more effective than NRT, and varenicline more effective than bupropion, it can be reasonably assumed that varenicline is more effective than NRT

10. Limitations to Usage Cost!!
On average $ 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 effective
Cost benefit analysis show that varenicline gave employers $ in savings compared to $ 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%
There isn’t a lot of insurance coverage for varenicline, leaving the patient to pay out of pocket for treatment.
Studies are showing that there is an increasing rate of coverage for pharmacotherapy for smoking cessation, so maybe someday varenicline will be included in the coverage.

11. 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!
I would use varenicline in patients that can afford it and do not have any pre-existing mental conditions such as bipolar disorder or schizophrenia.
There aren’t a lot of direct studies that show varenicline’s success rates compared to other drugs. This, along w/ more cost benefit analyses, could result in more insurance coverage for varenicline.

12. References
Arneric SP, Holliday M, Williams M. Neuronal Nicotinic Receptors: A Perspective in Two Decades of Drug Discovery Research. Biochemical Pharmacology October 25; 74(8):
Cahill K, Stead LF, Lancaster T :Department of Primary Healthcare. Nicotine Receptor Partial Agonists for Smoking Cessation. Cochrane Database of Systemic Reviews January 24 .
Foulds J. The Neurological Basis for Partial Agonist Treatment of Nicotine Dependence: Varenicline. International Journal of Clinical Practice May; 60(5):
Foulds J, Steinburg MB, Williams JM, Ziedonis DM. Developments in Pharmacotherapy for Tobacco Dependence: Past, Present, and Future January; 25(1):
Freedman R. Exacerbation of Schizophrenia by Varenicline. American Journal of Psychiatry August; 164(8): 1269.
Frishman WH. Smoking Cessation Pharmacology-Nicotine and Non-nicotine Preparations. Preventive Cardiology 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 July 5: 296(1):
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] April [cited 2007 October30]; 49(4). Available from
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 July 5; 296 (1):
Keating GM, Siddiqui AA. Varenicline: A Review of its Uses as an Aid to Smoking Cessation Therapy. CNS Drugs ; 20(1):

13. References cont.
Kohen I, Kremen N. Varenicline-Induced Manic Episode in a Patient with Bipolar Disorder. American Journal of Psychiatry August; 164(8):
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 , May-June; 42(3):
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 July; 28(7):
Tobin ML. Why Chose Varenicline (Chantix) for Smoking Cessation Treatment? Issues in Mental Health Nursing June; 28(6):
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 July 5; 296(1):
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 April; 23(4):
Wu P, Wilson K, Dimoulas P, Mills EJ. Effectiveness of Smoking Cessation Therapies: A Systematic Review and Meta-analysis. BMC Public Health December 11; 6: 300