Varenicline is an effective smoking cessation drug that works by partially activating and blocking nicotine receptors in the brain. The usual dosage is to titrate up to 1mg twice daily, starting varenicline one week before the target quit date. Common side effects include nausea, vomiting, and headaches. Counseling should encourage patients to follow the dosage schedule, try lowering the dose if side effects are intolerable, and not be discouraged by relapse.

1. Chantix ® (varenicline) for Smoking Cessation A presentation put together by myself and several pharmacy students. Posted with permission.

2. Learning Outcomes Recognize the epidemiology of tobacco use and its consequences. Know the nicotine pharmacology and its role in tobacco addiction. Identify some non-pharmacotherapies and pharmacotherapies used in nicotine addiction Know varenicline’s MOA, and dosage forms. Identify common and serious side effects, and precautions associated with the use of varenicline Evaluate efficacy of varenicline alone and compared to bupropion Provide counseling points for patients taking varenicline

3. Smoking Facts Cigarette smoking is responsible for 1 in every 5 deaths in the United States each year and it is the leading preventable cause of death It is estimated that 20.9% of all adults smoke cigarettes in the United States Cigarette smoking is more common among men (23.9%) than women (18.1% ) Cigarette smoking is more common among adults living below the poverty level (29.9%) compared to those living at or above the poverty level (20.6%) The largest number of smoking-related deaths are due to: lung cancer, heart disease, and the chronic lung diseases of emphysema, bronchitis, and chronic airway obstruction There are benefits to quit smoking at any age!!!

4. Pharmacology of Nicotine Nicotine binds to receptors in the brain, cardiovascular system and other parts of the body Cholinergic receptor agonist. Ach, NE  arousal Glutamate  learning, memory enhancement Beta-endorphin, GABA  reduce anxiety DA (cause of addiction)  pleasure, reward Withdrawal Symptoms: Anger/irritability Hunger/Weight gain Restlessness Sleep disturbances Cravings Difficulty concentrating

5. Methods for Assisting Smoking Cessation Non-pharmacological: behavioral cessation therapies individual, group, or telephone counseling are all effective Pharmacological: nicotine replacement therapy: transdermal, nasal spray, inhaler, gum, lozenges Bupropion SR (Zyban®) Chantix ® Clonidine: transdermal, oral Nortripyline (Pamelor ®) Anxiolytic agents

6. Varenicline MOA Nicotine activates the α 4 β 2 receptors This stimulates CNS mesolimbic dopamine system responsible for the reinforcement and reward experience associated with smoking. Varenicline binds to these receptors with high affinity as an agonist The agonistic effects are significantly less than those of nicotine The high affinity allows for competitive blocking of nicotine’s ability to stimulate the α 4 β 2 receptor

7. Efficacy of varenicline Varenicline has been found to be significantly more effective than placebo as a smoking cessation aid In one study those titrated to 1mg BID, had continuous quit rates of 54.6% at the end of treatment (9 to 12 weeks) compared to 11.6% in the placebo group (p<0.001) From weeks 9 to 52 the abstinence rate of these patients was 25.4% compared to 3.9% in the group receiving placebo (p<0.001) All groups also received smoking cessation counseling

8. Efficacy of varenicline compared to bupropion SR In another study, varenicline was shown to be significantly more effective than bupropion SR 43.9% abstinence in the varenicline group at the end of treatment (weeks 9-12) compared to 29.8% in the bupropion SR group (p<0.001) After 52 weeks 23% of the varenicline group remained abstinent compared to 14.6% of the bupropion SR group (p=0.004) All groups received brief ( < 10 min.) counseling for smoking cessation

9. Unique Dosing Information Days 1 – 3: 0.5 mg once daily Days 4 – 7: 0.5 mg twice daily Day 8 – End of treatment: 1 mg twice daily Patients should be treated with Chantix for 12 weeks Patients who cannot tolerate adverse effects may have the dose lowered temporarily or permanently. An additional 12 week period may be considered in an effort to enhance their long-term success Patients who are unsuccessful during the 12 weeks of initial therapy should be encouraged to make another attempt No need to adjust dose in mild to moderate renal impairment, hepatic impairment, or elderly (65-75 years)

10. Warnings and Precautions Use with caution in patients with severe renal dysfunction. Dosage adjustment is required when CrCl <30 mL/minute Initial 0.5 mg daily, max dose 0.5 mg BID Hemodialysis and ESRD: max dose 0.5mg daily Pregnancy category C Not recommended for patients < 18 years (safety and efficacy not established in this age group) Side effects are increased when used concurrently with other nicotine replacement therapy

11. Adverse Effects GI related side effects Nausea (30%) Abdominal pain Constipation Flatulence Vomiting CNS Insomnia Headache Somnolence Abnormal dreams Nightmare Others: rash, dyspnea, rhinorrhea, xerostomia Discontinuations due to adverse events were 8.6% for varenicline. Compared to 15.2% for bupropion SR and 9.0% for placebo.

12. Special Counseling Tips Set a target quit date Begin taking Chantix 1 week before quit date Take Chantix with food and water to decrease gastric upset Follow initial dose titration as laid out on packaging If adverse effects are intolerable or persistent, lowering the dose may be beneficial

13. More Counseling Tips Dosages of other medications may need to be adjusted, let your doctor or pharmacist know about all your medications Do not be discouraged by failed attempts, identify factors contributing to relapse and try again once they are addressed Consider signing up for Pfizer’s GETQUIT support program to receive daily updates by email or phone, activities, and a personal page aimed to help you quit and keep track of your progress www.get-quit.com

14. Summary Smoking is deadly Varenicline is a new safe and effective choice to help people quit The usual dosage is titrated to 1mg BID The major side effects of varenicline are nausea, vomiting, and headache Patients should take varenicline for a week before they quit smoking

15. References Centers for Disease Control and Prevention. Tobacco Use Among Adults—United States,2005. Morbidity and Mortality Weekly Report [serial online]. 2006;55(42):1145–1148 [cited 2006 Oct 30]. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5542a1.htm . Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing C, et al. Efficacy and Safety of the Novel Selective Nicotinic Acetylcholine Receptor Partial Agonist, Varenicline, for Smoking Cessation. Arch Intern Med. 2006 Aug;166:1571-7. Jorenby D, Hays J, Rigotti N, Azoulay S, Watsky E, Williams K, et al. Efficacy of Varencicline, an α 4 β 2 Nicotinic Acetylcholine Receptor Partial Agonist, vs Placebo or Sustained-Release Bupropion for Smoking Cessation. JAMA. 2006 July;296(1):56-63 Chantix ® (varenicline) Tablets [product information]. New York (NY):Pfizer, May 2006. Facts and comparisons online [monograph on the internet]. Wolters Kluwer Health Inc.; 2007 [cited 2007 Apr. 30]. Available from: http://online.factsandcomparisons.com . Koda-Kimble MA, Young LY, Krajan WA et. al. Applied Therapeutics: The clinical use of drugs. In: Corelli RL, Hudmon KS, editors. Tobacco use and dependence. Lippincott Williams and Wilkins, 2004. p 85(1-27).