Assisting a Quitter – The Medications Used in Smoking Cessation

1. Jim Thigpen, PharmD, BCPS ETSU Bill Gatton College of Pharmacy Assisting a Quitter – The Medications Used in Smoking Cessation

2. Learning Outcomes • Describe the pharmacotherapy used in smoking cessation • Determine the appropriate therapy to recommend for a specific patient • Describe patient expectations when using smoking cessation products

3. A Pediatric Disease1…. • Extent of harms to children caused by tobacco use and secondhand smoke exposure • Relationship of pediatric tobacco use and exposure to adult tobacco use • Existence of effective interventions to reduce the use • Documented underuse of those interventions Policy Statement – Tobacco Use: A Pediatric Disease, Pediatrics 124(5), Nov 2009

4. The role of Pediatricians…. • Provide counseling to expectant parents to quit using tobacco products and avoid SHS exposure during and after pregnancy • Assist new parents in their efforts to continue their tobacco use-abstinence or –cessation efforts after delivery • Counsel parents to reduce or eliminate children’s exposure to SHS • Counsel preadolescents and adolescents to prevent initiation • Counsel adolescents and parents to quit using tobacco

5. The role of Pediatricians…. • 85% of parents who smoke consider it acceptable for their child’s pediatrician to prescribe a smoking-cessation medication for them1 • In 2005, the American Medical Association adopted a policy statement supporting the practice of pediatricians addressing parental smoking2 American Medical Association H-490.917 Physician Responsibilities for Tobacco Cessation. Adopted June 2005, Chicago IL

6. What should you expect? • 18.4% will quit if you do nothing • 23.1% will quit if you intervene • Families with children ages 4-17 more likely • Interventions whose primary goal was cessation • Interventions that offered medications • Interventions with high follow-up rates Rosen LJ, Noach MB et al. Parental smoking cessation to protect young children: a systematic review and meta-analysis. Pediatrics 129(1) Jan 2012

7. Strategies and Evidence • Cessation rates are ↑ when smokers attended two or more sessions of ≥ 20 minutes • Motivating the unwilling patient • The five Rs • Relevant reasons to quit • Risks associated with continued smoking • Rewards for quitting • Roadblocks to successful quitting • Repetition of the counseling of subsequent visits

8. Counseling • There is a consistent relationship between more intensive counseling and abstinence from smoking • No counseling (11%) • 1 – 3 minutes (14%) • 4 – 30 minutes (19%) • 31 – 90 minutes (27%) • Counseling should be sympathetic and supportive, not confrontational • 1-800-QUIT-NOW (1-800-784-8669

9. Nonpharmacologic • Cold turkey • 5% success • Unassisted tapering • 5% success • Assisted tapering • QuitKey® • Computer-assisted behavior modification • 19-24% abstinence rate 1 year after quitting Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

10. Some basic pharmacology3…. • Nicotine is carried by tar particles to the lung alveoli and then to the brain • Nicotine binds with to nicotinic cholinergic receptors in the brain, leading to neurotransmitter release • Tolerance develops with chronic smoking, resulting in the proliferation of nicotine receptors and permitting higher levels of self-administration of nicotine • A lack of binding to these receptors due to decreased smoking results in withdrawal symptoms • About half of phenotypic variance in tobacco dependence is attributable to genetic influence Fiore MC, Baker TB. Treating smokers in the health care setting NEJM 2011;365:1222-31

11. Pharmacologic Methods • Three general classes of FDA-approved drugs for smoking cessation: • Nicotine Replacement Therapy (NRT) • Gum, patch, lozenge, nasal spray, inhaler • Psychotropics • Sustained-release bupropion (Zyban®) • Partial nicotinic receptor agonist • Varenicline (Chantix®)

12. Pharmacotherapy - Pregnancy • The clinical practice guideline states that pregnant smokers should be encouraged to quit without medication based on insufficient evidence of effectiveness and hypothetical concerns • NRT products are category D • Bupropion is category C • Varenicline is category C

13. PharmacotherapyNot recommended for….. • Smokeless tobacco users • No FDA indication • Individuals smoking < 10 cigarettes per day • Adolescents • OTC sales are restricted to ≥ 18 • NRT use in minors requires a prescription

14. NRT: Rationale for Use • Reduces physical withdrawal from nicotine • Eliminates the immediate, reinforcing effects of nicotine that is rapidly absorbed via tobacco smoke • Allows patient to focus on behavioral and psychological aspects of tobacco cessation • Use of NRT approximately doubles long-term quit rates relative to placebo Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

15. NRT Products • Polacrilex gum • Nicorette®, generics • Lozenge • Nicorette® Lozenge • Nicorette ® Mini Lozenge • Generics • Transdermal Patch • Nicoderm CQ ® • Generics • Nasal Spray • Nicotrol ® NS • Inhaler • Nicotrol ® Patients should stop using all forms of tobacco upon initiation of NRT

16. NRT Precautions • Patients with underlying cardiovascular disease • Recent myocardial infarction • Serious arrhythmias • Serious or worsening angina NRT products may be appropriate for these patients if they are under medical supervision

17. Nicotine GumNicorette® (GSK); generics • Resin complex • Nicotine • Polacrilin • Sugar-free chewing gum base • Contains buffering agents to enhance buccal absorption of nicotine • Available in 2mg, 4mg; original, cinnamon, fruit, mint (various), and orange flavors

18. Nicotine Gum Dosage based on current smoking patterns: Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

19. Nicotine Gum – Directions • Chew each piece slowly several times • Stop chewing at first sign of peppery taste • “park” gum between cheek and gum • Resume chewing when taste or tingle fades • Return to “park” when taste or tingle resumes • Repeat chew/park until most of the nicotine is gone (≈ 30 minutes) Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

20. Nicotine Gum • Use at least nine pieces per day • Do not eat or drink anything for 15 minutes before or while using nicotine gum • Nicotine polacrilex is buffered to pH 8.5 • Acidic beverages may reduce the pH of the saliva, reducing the buccal absorption of nicotine • Coffee, wine, juices, soft drinks • Chewing gum too rapidly can cause excessive nicotine release • Lightheadedness, N/V, irritation, hiccups, reflux Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

21. Nicotine Gum • Advantages • Satisfy oral cravings • Might delay weight gain (4 mg) • Therapy can be titrated to manage withdrawal symptoms • Flavors • Disadvantages • Need for frequent dosing • Dental work • Must use proper technique • Gum might not be socially acceptable

22. Nicotine Lozenge • Dosage is based on “time to first cigarette” as an indicator of nicotine dependence • Use the 2 mg strength if you smoke the first cigarette more than 30 minutes after waking • Use the 4 mg strength if you smoke the first cigarette less than 30 minutes after waking • Use is essentially identical to gum • Dosing intervals, titration, use, etc

23. Transdermal nicotine patchNicoderm® CQ, generics • Nicotine is well absorbed across the skin • Delivery to systemic circulation avoids hepatic first pass effect • Plasma nicotine levels are lower and fluctuate less than with smoking

24. Transdermal nicotine patch

25. Transdermal nicotine patch • Choose an area of skin on the upper body or upper outer part of the arm • Make sure the skin is clean, dry, hairless, and not irritated • Apply patch to different area each day • Do not use same area again for at least 1 week

26. Transdermal nicotine patch • Side effects to expect in first hour: • Mild itching • Burning • Tingling • Additional possible side effects: • Vivid dreams or sleep disturbances • Headache • Up to 50% will have local skin reactions

27. Nicotine nasal sprayNicotrol® NS (Pfizer) • Aqueous solution of nicotine (10 ml) • Each metered dose delivers • 50 mcl spray • 0.5 mg nicotine • ≈ 100 doses/bottle • Rapid absorption across nasal mucosa • More rapid onset compared to gum, patch, or inhaler • 26.7% 6-month abstinence rate

28. Nicotine nasal spray • One dose = 1 mg nicotine • (2 sprays, one 0.5 mg spray in each nostril) • Start with 1-2 doses per hour • Increase prn to maximum dosage of 5 doses per hour or 40 mg (80 sprays; ½ bottle) daily • For best results, patients should use at least 8 doses daily for the first 6-8 weeks • Gradual tapering over an additional 4-6 weeks

29. Nicotine inhaler • Start with at least 6 cartridges/day during the first 3-6 weeks of treatment • Increase to a maximum of 16 cartridges per day • In general, use 1 cartridge every 1-2 hours • Recommended duration of therapy is 3 months • Gradually reduce daily dosage over the following 6-12 weeks

30. Nicotine inhaler • During inhalation, nicotine is vaporized and absorbed across oropharyngeal mucosa • Inhale into back of throat or puff in short breaths • Nicotine in cartridges is depleted after about 20 minutes of active puffing • Cartridge does not have to be used all at once • Open cartridge retains potency for 24 hours • Mouthpiece is reusable; clean regularly

31. Nicotine inhaler • Side effects associated with the nicotine inhaler include: • Mild irritation of mouth or throat • Cough • Headache • Rhinitis • Dyspepsia • Severity generally rated as mild, and frequency of symptoms declined with use

32. Bupropion SRZyban®, generics • Non-nicotine • Sustained release antidepressant • Oral only • Estimated abstinence rate is 24.2%

33. Bupropion • Atypical antidepressant thought to affect levels of dopamine and norepinephrine • Clinical effects • ↓ craving for cigarettes • ↓ symptoms of nicotine withdrawal Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

34. Bupropion • Contraindications/Precautions • History of epilepsy • Other sources of bupropion (Wellbutrin®) • MAO inhibitors in preceding 14 days • Prior diagnosis of anorexia, bulemia, other psychiatric disorders (suicide risk) • Abrupt discontinuation of benzodiazepines, sedatives, or alcohol (↑ seizure risk) • Hepatic disease

35. Bupropion • Patients should begin therapy 1 – 2 weeks prior to their quit date to ensure target plasma levels • 150 mg once daily for 3 days, then BID • Duration is 7-12 weeks • Common side effects include: • Insomnia, dry mouth • Less common • Tremor, skin rash

36. Varenicline (Chantix®) • Binds with high affinity and selectivity to α4β2 neuronal nicotinic acetylcholine receptors • Stimulates low-level agonist activity • Competitively inhibits binding of nicotine • Clinical effects • ↓ symptoms of nicotine withdrawal • Blocks dopaminergic stimulation responsible for reinforcement & reward associated with smoking

37. Varenicline • Neurophychiatric symptoms and suicidality • Changes in mood • Psychosis/hallucinations/paranoia/delusions • Homicial ideation/hostility • Agitation/anxiety/panic • Suicidal ideation or attempts • Completed suicide

38. Varenicline • Patients should begin therapy 1 week prior to their quit date

39. Verenicline • Adverse Effects (> 5% and x2 higher than placebo) • Nausea • Sleep disturbances • Constipation • Flatulance • Vomiting • Vivid dreams (< 5%)

40. Second-line therapies • Clonidine • α2-adrenergic agonist that reduces sympathetic outflow that reduces the autonomic symptoms of withdrawal • May be beneficial • Nortriptyline • TCA • May be beneficial

41. Long-term (> 6 month) quit rates Nasal Spray Bupropion Patch

42. Combination Pharmacotherapy • Combination NRT • Patch + gum/inhaler/nasal spray • Bupropion + Nicotine patch

43. Comparative Daily Costs