1. Smoking Cessation: A Practical Overview of Pharmacotherapy Joseph Saseen, Pharm.D., FCCP, BCPS Professor University of Colorado Joseph.Saseen@ucdenver.edu

2. Learning Outcomes ● Apply recommendations from guidelines to customize clinical interventions to patients who use tobacco ● Compare and contrast advantages and disadvantages of various tobacco cessation pharmacotherapy products to

3. U.S. Department of Health and Human Services: Public Health Service (May 2008) Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

4. Potential Health Benefits of Smoking Cessation Time After Smoking 20 min BP, HR, peripheral circulation improve 24 hrs CO levels drop 48 hrs Nicotine eliminated; taste and smell improve 2-12 wks Lung function can improve 30% 3-9 mo SOB and coughing decrease 1 yr Risk of MI reduced 50% 10 yrs Risk of lung cancer reduced 50% 15 yrs Risk of MI and stroke reduce to level of nonsmoker

5. Nicotine Stimulates Dopamine Release ● High nicotine levels achived in 11 seconds from inhalation Nicotine and Tobacco Research 1999;1:s121-s125

6. 10 Key Guideline Recommendations 1.Repeated intervention and multiple attempts 2.Identify and document tobacco use status and treat every tobacco user 3.Treatments are effective: counseling and medications 4.Brief treatment is effective 5.Counseling is important: practical and social support http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

7. 10 Key Guideline Recommendations 6.Medications should be used whenever possible 7.Combination of counseling and medication more effective than either alone 8.Telephone quitline counseling is effective 9.Use motivational treatment if patients unwilling to quit 10. Insurance plans should include counseling and medication coverage http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

8. The “5 A’s” Model http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

9. Meta Analysis 2008 (n=18 studies) TreatmentArms (#) Estimated Odds Ration (95% CI) Estimated Abstinence Rates (95% CI) Medication Alone81.021.7 Medication and Counseling 391.4(1.2-1.6)27.6 (25.0-30.3) 0-1 Sessions plus Medication 131.021.8 2-3 Sessions plus Medication 61.4 (1.1-1.8)28.0 (23.0-33.6) 4-8 Sessions plus Medication 191.3 (1.1-1.5)26.9 (24.3-29.7) > 8 Sessions plus Medication 91.7 (1.3-2.2)32.5 (27.3-38.3) http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

10. First Line Medications Nicotine Replacement ●Nicotine gum ●Nicotine inhaler ●Nicotine lozenge ●Nicotine nasal spray ●Nicotine patch Oral Agents ●Bupropion SR ●Varenicline http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

11. Nicotine Gum Advantages ●May satisfy oral cravings ●May delay weight gain ●Patients can titrate therapy to manage withdrawal symptoms Disadvantages ●Gum chewing may not be socially acceptable ●May stick to dental work and dentures ●Proper chewing technique (Chew/Park) needed to minimize adverse effects ●Cannot eat or drink 15 minutes before or while using the nicotine gum

12. Nicotine Inhaler Advantages ●Patients can easily titrate therapy to manage withdrawal symptoms ●Mimics the hand-to- mouth ritual of smoking Disadvantages ●Initial throat or mouth irritation (in first week) ●Cartridges should not be stored in conditions >86 o F or <59 o F ●Patients with underlying bronchospastic conditions should use with caution

13. Nicotine Lozenge Advantages ●May satisfy oral cravings ●Easy to use and conceal ●Patients can titrate therapy to manage withdrawal symptoms Disadvantages ●Gastrointestinal side effects (nausea, hiccups, heartburn) may be bothersome ●Must allow slow dissolution for 20-30 minutes (no chewing) ●Should not eat or drink for 15 minutes before or while using the nicotine lozenge

14. Nicotine Nasal Spray Advantages ●Dose can be easily titrated to rapidly manage withdrawal symptoms Disadvantages ●Initial nasal or throat irritation can be bothersome (may last up to 3 weeks) ●Higher dependence potential relative to other NRT formulations ●Patients with chronic nasal disorders (e.g., rhinitis, polyps, sinusitis) or severe reactive airway disease should not use

15. Nicotine Patch Advantages ●Steady-state nicotine levels are achieved throughout the day ●Easy to use and conceal ●Fewer compliance issues are associated with the patch Disadvantages ●Patients cannot titrate dose ●Allergic reactions to the adhesive may occur ●Patients with underlying dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis) should not use the patch

16. Bupropion SR (Zyban) Advantages ●Oral formulation given BID that is easy to use ●May be beneficial for patients with coexisting depression ●Initiated before quit date ●No risk of nicotine toxicity if patient continues to smoke Disadvantages ●Increases seizure risk ●Several contraindications and precautions that may preclude use ●Side effects of insomnia and dry mouth

17. Varenicline (Chantix) Advantages ●Oral formulation given BID that is easy to use ●Initiate before quit date ●New mechanism of action for persons who previously failed using other medications Disadvantages ●May induce nausea in up 1/3 of patients (need to titrate) ●Post-marketing surveillance data stimulated FDA warning

18. Varenicline (Chantix): Package Insert Update WARNINGS and PRECAUTIONS Serious neuropsychiatric symptoms have occurred in patients being treated with CHANTIX. Some cases may have been complicated by the symptoms of nicotine withdrawal in patients who stopped smoking; however, some of these symptoms have occurred in patients who continued to smoke. All patients being treated with CHANTIX should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior.

19. Varenicline (Chantix): FDA Alert February 1, 2008 Recommendations and Considerations for Healthcare Professionals ● Monitor all patients taking Chantix for serious neuropsychiatric symptoms ● Serious psychiatric illness (e.g., schizophrenia, bipolar, major depressive disorder) may worsen ● Consider these safety concerns and alert patients about these risks http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm106540.htm

20. Varenicline (Chantix): FDA Alert February 1, 2008 Information for the patient ● Report any history of psychiatric illness prior to starting Chantix ● Be alert to changes in mood and behavior ● Immediately report changes in mood and behavior ● Vivid, unusual, or strange dreams may occur Medication Guide (5/16/08) ● http://www.fda.gov/downloads/Drugs/DrugSafety/UCM088569.pdf http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm106540.htm

21. Monotherapy TreatmentArms (#) Estimated Odds Ratio (95% CI) Estimated Abstinence Rates (95% CI) Placebo801.013.8 Nicotine Gum 6-14 wks > 14 wks 15 6 1.5 (1.2-1.7) 2.2 (1.5-3.2) 19.0 (16.5-21.9) 26.1 (19.7-33.6) Nicotine Inhaler62.1 (1.5-2.9)24.8 (19.1-31.6) Nicotine Nasal42.3 (1.7-3.0)26.7 (21.5-32.7) Nicotine Patch 6-14 wks >14 wks High-dose (>25mg) 32 10 4 1.9 (1.7-2.2) 1.9 (1.7-2.3) 2.3 (1.7-3.0) 23.4 (21.3-25.8) 23.7 (21.0-26.6) 26.5 (21.3-32.5) Bupropion SR262.0 (1.8-2.2)24.2 (22.2-26.4) Varenicline (2 mg/d)53.1 (2.5-3.8)33.2 (28.9-37.8) http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

22. Combination Pharmacotherapy TreatmentArms (#) Estimated Odds Ratio (95% CI) Estimated Abstinence Rates (95% CI) Nicotine Patch (>14 wk) + ad lib Nicotine Gum/Spray 33.6 (2.5-5.2)36.5 (28.6-45.3) Nicotine Patch + Nicotine Inhaler 22.2 (1.3-3.6)25.8 (17.4-36.5) Nicotine Patch + Bupropion SR 32.5 (1.9-3.4)28.9 (23.5-35.1) ●These combinations are considered “effective” according to guidelines http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

23. Cost of Pharmacotherapy http://www.drugstore.com

24. Bottom Line: Pharmacotherapy for Smoking Cessation All smokers trying to quit should be offered medication…. except when contraindicated or for specific populations for which there is insufficient evidence of effectiveness: Pregnant women Smokeless tobacco users Light smokers Adolescents http://www.surgeongeneral.gov/tobacco/treating_tobacco_use08.pd f

25. Plethora of Resources ● CO Quitline (www.coquitline.org)www.coquitline.org ● Fixnixer (www.fixnixer.com)www.fixnixer.com ● Become an Ex (www.becomeanex.com)www.becomeanex.com ● My Last Dip (www.mylastdip.com)www.mylastdip.com ● Cigarette is Dead (www.thecigaretteisdeadtimeline.com)www.thecigaretteisdeadtimeline.com ● Quit Doing it Labs (www.quitdoingitlabs.com)www.quitdoingitlabs.com ● Raise Smoke Free Kids (www.raisesmokefreekids.com)www.raisesmokefreekids.com

26. Quit Tips ●Make a quit plan. Pick a date and make a list of reasons you want to quit. ●Prepare for your quit date. This means getting rid of all tobacco-related items, such as ashtrays, lighters and matches. ●Ask your family and friends to support you in your quit attempt. Tell them your quit date and ask them to be supportive and understanding. ●Keep a picture of your loved ones. Tape a message to the picture that reminds you that you are quitting for them. Look at the picture and read the message anytime you have an urge to smoke. ●When you feel an urge to reach for a cigarette, try taking a walk, playing with your kids or running up and down the stairs instead of lighting up. ●For the first few days after you quit smoking, spend as much free time as possible in public places where smoking is not allowed. ●Reward yourself when you reach milestones in your quit attempt, such as buying yourself a new book or treating yourself to a nice dinner with a supportive friend. ●Keep healthy snacks, gum, mints and toothpicks around, and drink plenty of water. ●Try to avoid people, places or other trigger habits you typically associate with smoking. ●Take deep, slow breaths and imagine your lungs filling with clean, fresh air. ●Create a smoke-free rule for your home and car. Smoke-free environments can support you in the quitting process. ●Don´t give up. Most people have to try several times to quit smoking. You can do it. www.myquitpath.com