Varenicline

Drug for Smoking cessation

1. VARENICLINE Dr. Subodh Sharma Resident (First Year) Department of Psychiatry NMCTH, Birgunj , Nepal

2. Introduction It is a high-affinity  partial agonist  for the α4β2  nicotinic acetylcholine receptor  subtype ( nACh ) Used as pharmacotherapeutic agent for smoking cessation. Non nicotine drugs for smoking.

3. Approved by FDA in 2006 Use of  Cytisus plants as a smoking substitutes during  World War II  led to extraction of cytisine .  Cytisine   analogs  led to varenicline at  Pfizer.

4. Available options for Smoking Cessation Non pharmacological Behavior therapy (individual / group/ telephone quit line) Clinical counselling Pharmacological Nicotine replacement (patches/ gums/lozenges) Bupropion Varenicline

5. Studies on Varenicline A meta-analysis of randomized trials found that varenicline was more effective for smoking cessation than placebo (RR 2.27, 95% CI 2.02-2.55) Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev 2013; :CD009329. In another meta-analysis of randomized controlled trials, more patients were abstinent at 24 weeks with varenicline compared with both placebo and  nicotine  patch (RR 2.24, 95% CI 2.06-2.43; and RR 1.25, 95% CI 1.14-1.37 respectively) Cahill K, Lindson -Hawley N, Thomas KH, et al. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2016; :CD006103.

6. H ead-to-head double-blinded randomized controlled trial comparing multiple agents (varenicline, bupropion, nicotine patch) and placebo, varenicline was more effective in producing six months of tobacco abstinence than other drugs or placebo. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomized, placebo-controlled clinical trial . Varenicline is safe for use by tobacco users with chronic obstructive pulmonary disease (COPD) Tashkin DP, Rennard S, Hays JT, et al. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest 2011; 139:591.

7. Nonpharmacologic methods Method Versus minimal or usual care unless otherwise noted Risk ratio (95% CI) Behavioral counseling Individual counseling 1.57 (1.40-1.77) Group counseling 1.88 (1.52-2.33) Telephone quit line counseling 1.38 (1.19-1.61) Clinician counseling Brief advice 1.66 (1.42-1.94) Brief counseling 1.86 (1.60-2.15) Brief counseling (versus brief advice) 1.37 (1.20-1.56)

8. Pharmacologic methods Method (number of trials) Versus placebo unless otherwise noted Risk ratio (95% CI) First-line pharmacotherapies * Nicotine replacement [5] All types combined 1.55 (1.49-1.61) Combination [versus individual products] 1.25 (1.15-1.36) Patch (43) 1.64 (1.53-1.75) Gum (56) 1.49 (1.40-1.60) Lozenge (7) 1.52 (1.32-1.74) Inhaler (4) 1.90 (1.36-2.67) Nasal spray (4) 2.02 (1.49-2.73) Varenicline (27) 2.24 (2.06-2.43) Bupropion SR (46) 1.64 (1.52-1.77)

9. Mechanism of Action

10. Pharmacokinetics and Pharmacodynamics

11. Dosing Initial: Days 1 to 3: 0.5 mg once daily. (after food) Days 4 to 7: 0.5 mg twice daily. Maintenance (day 8 and later): 1 mg twice daily; may consider a temporary or permanent dose reduction if usual dose is not tolerated. Duration: Continue maintenance dose for at least 11 weeks (for a total of at least 12 weeks of treatment). May consider extended maintenance therapy based on individual patient risk : benefit; evidence suggests relapse prevention benefits with continuing therapy for up to 1 year.

12. Adverse effects Nausea: Dose-dependent nausea may occur; both transient and persistent nausea has been reported. Dosage reduction may be considered for intolerable nausea Neuropsychiatric effects: Post marketing cases of serious neuropsychiatric events (including depression, suicidal thoughts, and suicide) have been reported in patients with or without preexisting psychiatric disease Somnambulism: Cases of somnambulism, involving harmful behavior to self, others, or property, have been reported. Discontinue treatment if somnambulism occurs

13. Side effects Cardiovascular : Angina pectoris (4%), chest pain (3%), peripheral edema (2%) Central nervous system: Headache (12% to 19%), insomnia (9% to 19%), abnormal dreams (8% to 13%), irritability (11%), suicidal ideation (11%), depression (4% to 11%) Anxiety (8%), sleep disorder (3% to 5%) Gastrointestinal: Nausea (16% to 40%), vomiting (5% to 11%) Flatulence (6% to 9%), constipation (5% to 8%), diarrhea (6%), increased appetite (3% to 4%)

14. Use in Pregnancy FDA Category C Available data have not suggested increased risk for major birth defects as compared with women who smoke Studies are not conclusive of whether quitting smoking with varenicline reduses the risk of birth defects which are the result of smoking.

15. Cost A one-month supply of varenicline will cost approximately  $120  for the maintenance dose. Not available in Nepal Used and available in India as Varni 0.5mg tablet

16. References T. Varenicline.  Drugs Jiménez-Ruiz, C., Berlin, I. & Hering   Effect of Maintenance Therapy With Varenicline on Smoking CessationA Randomized Controlled Trial Serena Tonstad , MD, PhD ;  Philip Tønnesen , MD, PhD Varenicline ; A Review of its Use as an Aid to Smoking Cessation Therapy Gillian M. Keating & M. Asif A. Siddiqui  Varenicline for Tobacco Dependence J. Taylor Hays, M.D., and Jon O. Ebbert , M.D. UpToDate

17. Thank You !