Quitting for Good: A Tobacco Treatment Workshop for Community Pharmacists

Transcription

1 Quitting for Good: A Tobacco Treatment Workshop for Community Pharmacists Robin L. Corelli, PharmD, TTS UCSF School of Pharmacy Karen S. Hudmon, DrPH, MS, RPh, TTS Purdue College of Pharmacy Annual Meeting & Exposition Seattle, Washington March 22 25

2 Disclosures Drs. Corelli and Hudmon declare no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria.

3 CPE Information Target Audience: Pharmacists ACPE#: L01 P Activity Type: Application based

4 Supporter This activity is supported by independent educational grants from Pfizer Inc. a

5 Learning Objectives At the completion of this application based activity, participants will be able to: 1. Summarize recent data regarding the efficacy and safety of available medications for treating tobacco use and dependence. 2. Develop a treatment regimen that incorporates effective medications for smoking cessation, including drug(s), dose(s), route(s), and frequency of administration. 3. Explain the role of electronic nicotine delivery systems in smoking cessation. 4. Discuss the significance of current statewide protocols allowing pharmacists to prescribe tobacco cessation products without obtaining a prescription from a medical prescriber.

6 Assessment Question #1 Ms. Lee, 67 yrs, requests help in selecting a medication for quitting. She currently smokes 20 cigarettes per day; the first one within 10 minutes of waking. She has dentures and is allergic to bandage adhesives (rash). Other medical problems include hypertension and eczema. She has never tried to quit before and likes the idea of an OTC nicotine replacement therapy product. Which of the following regimens is most appropriate during the first month of treatment? A. Nicotine patch 21 mg daily B. Nicotine gum 2 mg, 1 piece every 1 2 hours while awake C. Nicotine lozenge 4 mg, 1 piece every 1 2 hours while awake D. Nicotine inhaler, 1 cartridge every 1 2 hours while awake

7 Assessment Question #2 Which of the following statements is TRUE regarding electronic nicotine delivery systems (ENDS; e.g., e cigarettes)? A. ENDS are a safe alternative to cigarette smoking B. ENDS have lower exposure to carcinogens and toxins than tobacco smoke C. ENDS have a lower risk for nicotine dependence D. ENDS are more effective for cessation than nicotine replacement therapy

8 Assessment Question #3 Which of the following is TRUE based on outcomes of the FDA mandated EAGLES study? A. Combination nicotine replacement therapy was more effective than patch monotherapy for smoking cessation B. The boxed warning was removed from varenicline and bupropion SR for smoking cessation C. The placebo arm of the trial exhibited a significantly lower incidence of moderateto severe neuropsychiatric side effects than participants receiving bupropion SR or varenicline D. Participants with a mental health diagnosis had similar rates of neuropsychiatric events when compared to participants without a mental health diagnosis

9 Assessment Question #4 Which of the following is TRUE regarding the role of pharmacists in treating tobacco use and dependence? A. All states with prescriptive authority for tobacco cessation require pharmacists to complete relevant training. B. California was the first state to permit pharmacists to prescribe prescription medications for smoking cessation. C. Six month quit rates are 5 10% for patients who receive assistance from a pharmacist for quitting. D. Brief interventions are effective in helping patients quit.

10 The content for this session derives from the Rx for Change: Clinician Assisted Tobacco Cessation program. Copyright The Regents of the University of California. All rights reserved.

11 CIGARETTE SMOKING is the chief, single, avoidable cause of death in our society and the most important public health issue of our time. C. Everett Koop, M.D., former U.S. Surgeon General

12 TOBACCO DEPENDENCE: A 2 PART PROBLEM Tobacco Dependence Physiological The addiction to nicotine Treatment Behavioral The habit of using tobacco Treatment Medications for cessation Behavior change program Treatment should address the physiological and the behavioral aspects of dependence. 12

13 PHARMACOTHERAPY Clinicians should encourage all patients attempting to quit to use effective medications for tobacco dependence treatment, except where contraindicated or for specific populations* for which there is insufficient evidence of effectiveness. * Includes pregnant women, smokeless tobacco users, light smokers, and adolescents. Medications significantly improve success rates. Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

14 FIRST LINE PHARMACOTHERAPIES Nicotine gum Nicorette (OTC) Generic nicotine gum (OTC) Nicotine lozenge Nicorette / Nicorette Mini (OTC) Generic nicotine lozenge (OTC) Transdermal nicotine patch NicoDerm CQ (OTC) Generic nicotine patches (OTC) Nicotine oral inhaler Nicotrol (Rx) Nicotine nasal spray Nicotrol NS (Rx) Bupropion SR tablets Zyban (Rx) Generic (Rx) Varenicline tablets Chantix (Rx) These are the only medications approved by the FDA for smoking cessation. 14

15 NICOTINE GUM and LOZENGE Available: 2 mg, 4 mg; various flavors (OTC) Pros: Oral substitute for tobacco Can titrate to manage withdrawal symptoms Might delay weight gain Used in combination with other agents to manage situational urges Relatively inexpensive Cons: Frequent dosing = poor adherence Gastrointestinal side effects might be bothersome Dental work/jaw issues (gum only) Proper chewing technique is necessary (gum only) Gum chewing might not be acceptable/desirable

16 TRANSDERMAL NICOTINE PATCH Available: 21 mg, 14 mg, 7 mg (OTC) Pros: Once daily dosing Can use in combination with other agents; delivers consistent nicotine levels over 24 hours Of all nicotine replacement products, use is least obvious Relatively inexpensive Cons: Cannot be titrated to acutely manage withdrawal symptoms Not recommended for use with dermatologic conditions

17 NICOTINE ORAL INHALER Available: 10 mg cartridge delivers 4 mg inhaled vapor for absorption across buccal mucosa (Rx) Pros: Oral substitute Can titrate to manage withdrawal symptoms Mimics hand to mouth ritual of smoking Can use in combination with other agents to manage situational urges Cons: Frequent dosing = poor adherence Cartridges might be less effective in cold environments ( 60 F) Cost of treatment

18 NICOTINE NASAL SPRAY Available: 10 ml bottle; 0.5 mg per spray (Rx) Pros: Can titrate to more closely manage withdrawal symptoms Can use in combination with other agents to manage situational urges Cons: Frequent dosing = poor adherence Nasal administration; nasal irritation often problematic Not recommended for use with chronic nasal disorders or severe reactive airway disease Cost of treatment

19 BUPROPION SR Available: 150 mg tablets (Rx) Pros: Twice daily oral dosing Might be beneficial in patients with depression Can use in combination with NRT Relatively inexpensive (generic formulations) Cons: Seizure risk is increased Several contraindications and precautions / more extensive screening Patients must be monitored for potential neuropsychiatric symptoms

20 VARENICLINE Available: 0.5 mg and 1.0 mg tablets (Rx) Pros: Twice daily oral dosing Offers a different mechanism of action Most effective agent for cessation when used as monotherapy Cons: Nausea (28%): take after eating and with a full glass of water Insomnia/sleep disturbances Patients must be monitored for potential neuropsychiatric symptoms Cost of treatment

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24 Patient Encounter #1

25 ASKING ABOUT TOBACCO USE ASK about tobacco use with a tone that conveys sensitivity, concern, and is non judgmental Do you smoke or use other types of tobacco or nicotine, such as e cigarettes? It s important for us to have this information so we can check for any potential interactions with tobacco smoke and your other medicines. We ask all of our patients, because tobacco smoke can affect how well some medicines work. We care about your health, and we have resources to help our patients quit smoking. Has there been any change in your smoking status?

26 PHARMACOKINETIC DRUG INTERACTIONS with TOBACCO SMOKE Drugs that may have a decreased effect due to induction of CYP1A2: Bendamustine Haloperidol Tasimelteon Caffeine Olanzapine Theophylline Clozapine Erlotinib Fluvoxamine Pirfenidone Riociguat Ropinirole Irinotecan (clearance increased due to increased glucuronidation of active metabolite) Smoking cessation will reverse these effects. Kroon LA. Am J Health-Syst Pharm 2007;64:

27 PHARMACODYNAMIC DRUG INTERACTIONS with TOBACCO SMOKE Smokers who use combined hormonal contraceptives have an increased risk of serious cardiovascular adverse effects: Stroke Myocardial infarction Thromboembolism This interaction does not decrease the efficacy of hormonal contraceptives. Women who are 35 years of age or older AND smoke at least 15 cigarettes per day are at significantly elevated risk. 27

28 DRUG INTERACTIONS with TOBACCO SMOKE: SUMMARY Clinicians should be aware of patients tobacco use status: Clinically significant interactions result from the combustion products of tobacco smoke, not from nicotine. Constituents in tobacco smoke (e.g., polycyclic aromatic hydrocarbons) may enhance the metabolism of other drugs, resulting in an altered pharmacologic response. Changes in smoking status might alter the clinical response to the treatment of a wide variety of conditions. Drug interactions with smoking should be considered when patients start smoking, quit smoking, or markedly alter their levels of smoking.

29 BRIEF COUNSELING: ASK, ADVISE, REFER ASK ADVISE REFER about tobacco USE tobacco users to QUIT to other resources Patient receives assistance from other resources, with follow-up counseling arranged ASSIST ARRANGE

30 BRIEF COUNSELING: ASK, ADVISE, REFER Brief interventions have been shown to be effective* In the absence of time or expertise: Ask, advise and refer to other resources, such as local group programs or the toll free quitline QUIT NOW This brief intervention can be implemented in less than 1 minute. *Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

31 REFERRAL RESOURCES: TOBACCO QUITLINES Tobacco cessation counseling, provided at no cost via telephone to all Americans Staffed by highly trained specialists Up to 4 6 personalized sessions (varies by state) Tobacco quitlines in some states offer pharmacotherapy at no cost (or at a reduced cost) 28.1% success rate for patients who use the quitline and a medication for cessation (vs 12.7% for quitline use alone)* Most health-care providers, and most patients, are not familiar with tobacco quitline services. *Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

32 TOBACCO QUITLINES: WHEN a PATIENT CALLS the QUITLINE Caller is routed to language appropriate staff Brief Questionnaire Contact and demographic information Smoking behavior Choice of services Individualized telephone counseling Quitting literature mailed within 24 hours Referral to local programs, as appropriate Quitlines have broad reach and are recommended as an effective strategy in the Clinical Practice Guideline. 32

33 REFERRAL RESOURCES: ON LINE TOBACCO ASSISTANCE Quitnet.com* Operated by MeYou Health; longest running web based tobacco cessation program (since 1995) Active community of registered participants; provides 24/7/365 social support Becomeanex.org Operated by Truth Initiative and Mayo Clinic Nicotine Dependence Center More than 800,000 registered participants; provides 24/7/365 social support Smokefree.gov* Created by National Cancer Institute Tailored programs for veterans, women, teens and adults >60 years of age Free evidence-based resources to develop a personalized quit plan * Mobile app version also available.

34 ASK ADVISE REFER PHARMACY PRACTICE MODEL 2 ADVISE to quit (pharmacist or technician) 3a 3b If NOT ready to quit in next 30 days If ready to quit in next 30 days Establish as a resource for quitting; passive referral to quitline Time 1 ASK all patients about tobacco use (pharmacist or technician) 4 SELECT and COUNSEL on appropriate use of pharmacotherapy (pharmacist) 5 REFER to other resources (pharmacist or technician) Hudmon KS, Corelli RL, et al. J Am Pharm Assoc 2018;58:

35 Patient Encounter #2

36 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 1: ASK What medications have you tried in the past? For each medication, ask about: Strength and dosage Frequency of administration Duration of therapy Adverse effects experienced

37 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 1: ASK (cont d) Did you receive any professional advice or enroll in a quitting support program? If yes: Tell me what you liked, or didn t like, about the assistance you received. If no: What was your reasoning for not seeking advice or enrolling in a program?

38 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 2: ADVISE The best way to quit is to combine a smoking cessation medication with a support program. Would it be helpful to discuss the medication options that would be appropriate for you? If yes, then review: Current level and patterns of tobacco use Contraindications/precautions for use Advantages/disadvantages Personal preference and cost considerations

39 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 2: ADVISE (cont d) Considerations in patients with previous failed quit attempts using medication(s) for cessation If prior medication was used correctly, was well tolerated, and appeared to have been effective: Consider repeating same medication in combination with an enhanced behavioral support program If prior medication was used incorrectly: Carefully review usage instructions Emphasize adherence (e.g., daily use and full duration of treatment regimen)

40 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 2: ADVISE (cont d) If prior medication was used correctly but did not control withdrawal, symptoms, or If the patient prefers a different medication: Review other options, including single agent and combination therapy Re emphasize importance of the behavioral aspects of quitting

41 TOBACCO DEPENDENCE: A 2 PART PROBLEM Tobacco Dependence Physiological The addiction to nicotine Treatment Behavioral The habit of using tobacco Treatment Medications for cessation Behavior change program Treatment should address the physiological and the behavioral aspects of dependence. 41

42 SMOKERS WHO HAVE RELAPSED AFTER USING MEDICATIONS Step 3: REFER to a behavior change program Here are some suggestions. Which do you think would work best for you? QUIT NOW, national toll free telephone quitline All products include free access to a behavior change program; refer to instructions for enrollment procedures Hospital based or other local resources (e.g., a group program) On line cessation programs Local provider specializing in cessation

43 IDENTIFY KEY ISSUES to STREAMLINE PRODUCT SELECTION* Do you prefer a prescription or nonprescription medication? Would it be a challenge for you to take a medication frequently throughout the day (e.g., a minimum of 9 times)? With the exception of the nicotine patch, bupropion, and varenicline, all other smoking cessation medications require frequent dosing throughout the day. If patient is unable to adhere to the recommended dosing, short acting NRT products should be ruled out as monotherapy because they will be ineffective Asking these two questions will significantly reduce the time required for product selection. *Product-specific screening for warnings, precautions, contraindications, and personal preferences is also essential.

44 COMBINATION PHARMACOTHERAPY Regimens with enough evidence to be recommended first line Combination NRT Long acting formulation (patch) Produces relatively constant levels of nicotine PLUS Short acting formulation (gum, inhaler, lozenge, nasal spray) Allows for acute dose titration as needed for nicotine withdrawal symptoms Bupropion SR + Nicotine Patch

45 PLASMA NICOTINE CONCENTRATIONS for NICOTINE CONTAINING PRODUCTS 25 Cigarette 20 Cigarette Moist snuff Moist snuff Plasma nicotine (mcg/l) Nasal spray Inhaler Lozenge (2mg) Gum (2mg) 0 1/0/ /10/ /20/1900 1/30/1900 2/9/ /19/ /29/ Time (minutes) Patch NRT products should be taken to PREVENT withdrawal.

46 COMPARING MEDICATION TREATMENT OPTIONS Multiple Treatment Comparison Meta-Analysis Comparison Odds ratio (95% CI) Nicotine gum vs Placebo 1.7 (1.5, 1.9) Bupropion SR vs Placebo 1.9 (1.6, 2.1) Nicotine patch vs Placebo 1.9 (1.7, 2.1) Other NRT* vs Placebo 2.0 (1.8, 2.4) Combination NRT vs Placebo 2.7 (2.1, 3.7) Varenicline vs Placebo 2.9 (2.4, 3.5) *Includes nicotine nasal spray, lozenge, and inhaler Cahill et al. (2013). Cochrane Database Syst Rev 5:CD

47 COMPARATIVE DAILY COSTS OF THERAPY $/day $18 $16 $14 $12 $10 $8 $6 $4 $2 Average $/pack of cigarettes, $6.26 $0 Bupropion Gum Lozenge Patch Nasal spray Inhaler SR Varenicline Trade $5.49 $4.23 $3.49 $8.75 $14.95 $8.25 $15.90 Generic $1.90 $3.33 $1.52 $2.58 *Wholesale acquisition cost from Red Book Online. Thomson Reuters, January 2019.

48 PATIENT CASE: ANDY Andy, 53 yo male with hypertension, hyperlipidemia, depression, chronic rhinitis Current medications: Amlodipine 10 mg daily for hypertension Atorvastatin 20 mg daily for hyperlipidemia Bupropion XL 300 mg daily for depression Triamcinolone (55 mcg/spray), 1 spray in each nostril daily for rhinitis Wants to quit in the next month What questions do you want to ask Andy?

49 KEY CONSIDERATIONS for ANDY Tobacco use history Current use: 1 pack per day x 35 years; smokes within 10 min of waking Prior quit attempts: many ; longest duration tobacco free = 1 week Never received counseling; does not like idea of a group program Triggers to smoke: after waking; drinking coffee/alcohol, stress, other smokers Reasons for relapse: felt on edge, couldn t concentrate, stress, other smokers Key issues for upcoming quit attempt Reasons, motivation for wanting to quit: wants to prevent stroke/mi Readiness (9/10); Importance (10/10); Confidence (6 7/10) Other concerns: withdrawal symptoms during past quit attempt, being around other smokers, cost of treatment What additional questions do you want to ask Andy?

50 MEDICATION SELECTION for ANDY Key considerations for medication selection: Previous failed quit attempts with monotherapy (patch, gum) Challenges adhering with complex regimens Currently taking bupropion XL 300 mg daily for depression Concerned about cost of therapy Chronic rhinitis

51 AUDIENCE POLL & DISCUSSION Which of the following treatment options is most appropriate for Andy for the initial month of therapy? (select all that apply) A. Nicotine patch 21 mg daily B. Nicotine gum 4 mg every 1 2 hours while awake C. Nicotine inhaler, 1 cartridge every 1 2 hours while awake D. Nicotine nasal spray, 1 spray each nostril every 1 2 hours while awake E. Bupropion SR 150 mg twice daily F. Varenicline 1 mg twice daily G. Nicotine patch 21 mg daily + nicotine lozenge 4 mg every 1 2 hours prn H. I don t know

52 TOBACCO DEPENDENCE: A 2 PART PROBLEM Tobacco Dependence Physiological Behavioral The addiction to nicotine Treatment The habit of using tobacco Treatment Medications for cessation Behavior change program Readiness (9/10) Importance (10/10) Confidence (6 7/10)

53 Patient Encounter #3

54 ELECTRONIC NICOTINE DELIVERY SYSTEMS (ENDS): BACKGROUND Devices similar in appearance to cigarettes, cigars, pipes, or pens Battery operated devices that vaporize liquid formulations of nicotine for inhalation Simulates smoking but does not involve combustion of tobacco Also known as: E cigarette E hookah, Hookah pen Vapes, Vape pen, Vape pipe Electronic nicotine delivery system Image from: cigarettes under aliases elude the authorities.html

55 ENDS: DEVICE VARIABILITY Product Disposable Rechargeable Pen style Tank style Characteristics Cigarette shaped; battery + cartridge with atomizer; not rechargeable Cigarette shaped; rechargeable battery connects to atomizer; often contains element to regulate inhalations Larger device, often with higher capacity battery; refillable cartridge; manual switch to regulate inhalations Much larger; higher capacity battery; large refillable cartridge; easily modified Images from Grana et al.,

56 NICOTINE SOLUTIONS (E JUICE) CONSTITUENTS Solutions generally contain: Propylene glycol (PG) Vegetable glycerin (VG) Flavorings (>7,000 available) Nicotine (0 36 mg/ml)

57 NICOTINE POD SYSTEMS Do not resemble cigarettes Nicotine liquid stored in small plastic cartridges (aka pod ) Produce less vapor compared to tank models JUUL Sourin Bo PHIX Images from: juul.com; suorinusa.com; bovaping.com; phixvapor.com

58 COMPARATIVE PLASMA NICOTINE CONCENTRATIONS: CIGARETTE vs JUUL During , ENDS use among high school students increased by 78% (from 11.7% to 20.8%; p<0.001) 1 1 Cullen et al., MMWR Morb Mortal Wkly Rep 2018;67: Graph from cigarettes 2/tobacco youth/

59 ENDS for SMOKING CESSATION RANDOMIZED CONTROLLED TRIAL In smokers motivated to quit, are ENDS efficacious for smoking cessation? Characteristic Bullen et al., 2013 Study population Sample size 657 Intervention arms Behavioral support Period of intervention Duration of follow up Primary outcome Motivated to quit 16 mg e cig 21 mg nicotine patch 0 mg e cig Minimal 13 weeks 6 months Continuous abstinence at 6 months, verified by expired carbon monoxide Bullen et al., Lancet 2013;382:

60 ENDS for SMOKING CESSATION RANDOMIZED CONTROLLED TRIAL Results: Continuous Abstinence Nicotine e cigarette vs Nicotine transdermal patch vs Placebo e cigarette 16 mg e cigarette (n=289) 21mg nicotine patch (n=295) Placebo e cigarette (n=73) 6 months 21 (7.3%) 17 (5.8%) 3 (4.1%) No significant differences Bullen et al., Lancet 2013;382:

61 ENDS for SMOKING CESSATION RANDOMIZED CONTROLLED TRIAL ENDS can reduce the desire to smoke and reduce nicotine withdrawal symptoms Using ENDS, some smokers reduced the number of cigarettes smoked or quit smoking Adverse effects: No serious events reported No significant differences between nicotine patch and ENDS Bullen et al., Lancet 2013;382:

62 ENDS for SMOKING CESSATION RANDOMIZED CONTROLLED TRIAL Strengths Large trial Randomized design with comparison groups Verified continuous abstinence at 6 months Limitations First generation ENDS formulation; now antiquated Low adherence in nicotine patch arm Differential methods for receiving patch vs ENDS products High loss to follow up; higher in patch vs ENDS group Little behavioral support Underpowered Bullen et al., Lancet 2013;382:

63 ENDS for CESSATION RECOMMENDATIONS FOR CLINICIANS Assess ENDS use when screening for tobacco use Actively discourage use of ENDS with current non smokers Until more is known about the potential risks, ENDS should not be promoted as a safe alternative to smoking ENDS have not been proven to be effective for cessation Until long term efficacy data are available, clinicians should recommend evidence based, FDA approved treatments for smoking cessation

64 ENDS for CESSATION RECOMMENDATIONS FOR CLINICIANS (cont d) Evidence suggests that ENDS use is less harmful than smoking Increased risks with dual use (tobacco + ENDS) ENDS might have a role for patients who are unable to quit smoking using proven methods Weigh risks and benefits on a case by case basis Currently, ENDS are unregulated; most contain low toxic constituents (in lower concentrations compared to tobacco smoke) Advise patients to quit smoking entirely even low levels of smoking impose significant health risks

65 ENDS: HEALTH RISKS OF DUAL USE with CIGARETTES Health Consequences of Light Smoking Smoking 1 4 cigarettes/day is associated with significantly higher risk of dying from ischemic heart disease (both sexes) and lung cancer (females) 1 Light and intermittent smoking is associated with comparable risk for cardiovascular disease as daily smoking 2 Light smokers (1 10 cigarettes/day) have higher all cause mortality risk than do never smokers 3 There is no risk free level of exposure to tobacco smoke 1 Bjartveir & Tverdal, Tobacco Control 2005;14: Schane et al., Circulation 2010;121: Inoue Choi et al., JAMA Int Med 2017;177:87 95.

66 ENDS for CESSATION: U.S. POSITION The current evidence is insufficient to recommend electronic nicotine delivery systems (ENDS) for tobacco cessation. Clinicians should direct patients who smoke tobacco to other cessation interventions with established effectiveness and safety. Siu AL; for the U.S. Preventive Service Task Force Ann Int Med 2015;163:

67 Patient Encounter #4

68 BUPROPION SR and VARENICLINE: WARNINGS AND PRECAUTIONS Neuropsychiatric symptoms and suicide risk Changes in mood (including depression and mania) Psychosis/hallucinations/paranoia/delusions Homicidal ideation Aggression/hostility/anxiety/panic Suicidal ideation, suicide attempt, completed suicide FDA boxed warning removed Dec 2016 Advise patients to stop taking bupropion SR or varenicline and contact a health care provider immediately if symptoms such as agitation, depressed mood, or changes in behavior or thinking that are not typical are observed or if the patient develops 68 suicidal ideation or suicidal behavior.

69 Anthenelli RM et al. Lancet 2016;387:

70 THE EAGLES STUDY FDA mandated clinical trial 8,144 participants (4,116 with a psychiatric disorder; 4,028 without) 140 multinational centers 24 week, double blind; active and placebo controlled: Varenicline: standard dosing, 12 weeks Bupropion SR: standard dosing, 12 weeks Nicotine patch: 21 mg/day with standard taper, 12 weeks Placebo: 12 weeks All arms: 13 counseling visits, 11 telephone calls Follow up through 24 weeks Primary outcome: continuous abstinence EAGLES = Evaluating Adverse Events in a Global Smoking Cessation Study Anthenelli RM et al. Lancet 2016;387:

71 THE EAGLES STUDY: Efficacy Data % achieving continuous abstinence, weeks 9 24 Patient cohort Varenicline Bupropion SR Nicotine patch Placebo Non psychiatric (n=4,116) Psychiatric (n=4,028) 25% 19% 18% 11% 18% 14% 13% 8% Highest efficacy with varenicline 71 Anthenelli RM et al. Lancet 2016;387:

72 Patient Encounter #5

73 THE EAGLES STUDY: Neuropsychiatric Safety Data Incidence of moderate or severe neuropsychiatric adverse events Patient cohort Varenicline Bupropion SR Nicotine patch Placebo Non psychiatric (n=4,116) Psychiatric (n=4,028) 1.3% 2.2% 2.5% 2.4% 6.5% 6.7% 5.2% 4.9% No significant differences in neuropsychiatric events by treatment arm 73 Anthenelli RM et al. Lancet 2016;387:

74 FDA Statement

75 CARDIOVASCULAR RISKS of SMOKING CESSATION MEDICATIONS Concern: Risk of myocardial infarction if a patient smokes while using NRT NRT is a safe treatment for smokers with cardiovascular disease (CVD) Concern: Bupropion increases blood pressure; package insert includes precautions about hypertension Clinical trials with participants who smoke: no increased incidence of cardiovascular adverse events Concern: Cardiovascular events in patients taking varenicline Package insert warns about possibility of increased rate of CV events in smokers with established CVD Benowitz NL et al. JAMA Int Med 2018;1;178(5):

76 Study Objective: To compare the relative cardiovascular safety risk of smoking cessation treatments Benowitz NL et al. JAMA Int Med 2018;1;178(5):

77 THE EAGLES STUDY: Cardiovascular Safety Data* Primary endpoint: Major adverse cardiovascular event (MACE): Time to development of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke during treatment Secondary endpoints: Occurrence of MACE or other pertinent cardiovascular events: e.g., new onset or worsening peripheral vascular disease requiring intervention, coronary revascularization, or hospitalization for unstable angina (MACE+) * Included participants in the EAGLES study (24 weeks), plus a subset of 4,595 who agreed to an additional 28 weeks of follow up (total, 52 weeks). Benowitz NL et al. JAMA Int Med 2018;1;178(5):

78 THE EAGLES STUDY: Cardiovascular Safety Data Incidence of MACE Time period Varenicline n=2,016 Bupropion SR n=2,006 Nicotine patch n=2,022 Placebo n=2,014 During treatment day follow up End of study* * Last visit in the EAGLES study or the EAGLES extension trial (an additional 28 weeks of treatment). Incidence of MACE was low; no significant differences between psychiatric/non-psychiatric cohorts or by treatment arm Benowitz NL et al. JAMA Internal Medicine 2018;1;178(5):

79 THE EAGLES STUDY: Cardiovascular Safety Data Incidence of MACE+ Time period Varenicline n=2,016 Bupropion SR n=2,006 Nicotine patch n=2,022 Placebo n=2,014 During treatment day follow up End of study* * Last visit in the EAGLES study or the EAGLES extension trial (an additional 28 weeks of treatment). Incidence of MACE+ was low; no significant differences between psychiatric/non-psychiatric cohorts or by treatment arm 79 Anthenelli RM et al. Lancet 2016;387:

80 THE EAGLES STUDY: Cardiovascular Safety Summary No evidence that cessation medications increase risk for serious cardiovascular disease or cardiovascular adverse events Did not include patients with acute or unstable cardiovascular disease In the general population of individuals who smoke, the benefit of improved cardiovascular health from pharmacotherapy assisted smoking cessation exceeds any risk of medication induced cardiovascular harm. Benowitz NL et al. JAMA Internal Medicine 2018;1;178(5):

81 Patient Encounter #6 INSERT BRIEF VIDEO SINCE WHEN DID PHARMACISTS START ASKING PATIENTS WHETHER THEY SMOKE?

82 THE EXPANDING ROLE of the PHARMACIST in TOBACCO CESSATION 1999 present: Integration of tobacco cessation into pharmacy school curricula 2004: New Mexico becomes the first state to permit pharmacists to prescribe all cessation medications No negative reports related to pharmacists prescribing 6 month quit rates are estimated at 18% 1 to 25% 2 Comparable to other interventions Most commonly prescribed medications: nicotine replacement therapy (38.4%), varenicline (30.7%) 1 35% of patients assisted were non white (21% Hispanic); 53% had no health insurance 1 1 Shen Z et al. Journal of Managed Care Pharmacy 2014;20(6): Khan N et al. Drug, Alcohol, and Substance Abuse 2012;46:

83 THE EXPANDING ROLE of the PHARMACIST in TOBACCO CESSATION 2017: To address public health challenges, the Center for Medicaid Services recommends that states allow pharmacists to prescribe medications such as smoking cessation medications, naloxone, and vaccinations Prescriptive authority strategies for cessation: Collaborative practice agreements (CPAs) Autonomous models of prescribing: Independent prescribing (Idaho) Statewide protocol (others) National Alliance of State Pharmacy Associations web site: cessation/

84 THE EXPANDING ROLE of the PHARMACIST in TOBACCO CESSATION State OTC NRT Prescription NRT Varenicline and bupropion SR Required hours of training Arizona 2 hours every 2 years California 2 hours; then 1 hour every 2 years Colorado Required; # of hours not specified Idaho Required; # of hours not specified Indiana None / PENDING final signature by State Kentucky Required; # of hours not specified Maine Not described New Mexico 2 hours every 2 years In process: AR, CT, IA, IL, MA, MD, MN, MO, OR, PA, RI, TX, VA, VT Updated and adapted from: Adams AJ, Hudmon KS. J Am Pharm Assoc 2018;58:

85 ASK ADVISE REFER Accessible, extended hours/weekends/holidays 1 Dispensing medications to treat tobacco related diseases / immunizations Enhanced access to uninsured/underinsured, rural areas Decisions to quit are often spontaneous Medications are safe and effective / patients need more timely access to the most effective cessation modalities Comparable efficacy as other interventions Team with tobacco quitline (1 800 QUIT NOW) Implementing Ask Advise Refer (without prescribing) in community pharmacies results in meaningful increases in the number of patients who call the quitline 2 1 Adams AJ, Hudmon KS. J Am Pharm Assoc 2018;58: Hudmon KS, Corelli RL, et al. J Am Pharm Assoc 2018;58:

86 ASK ADVISE REFER PHARMACY PRACTICE MODEL 2 ADVISE to quit (pharmacist or technician) 3a 3b If NOT ready to quit in next 30 days If ready to quit in next 30 days Establish as a resource for quitting; passive referral to quitline Time 1 ASK all patients about tobacco use (pharmacist or technician) 4 SELECT and COUNSEL on appropriate use of pharmacotherapy (pharmacist) 5 REFER to other resources (pharmacist or technician) Hudmon KS, Corelli RL, et al. J Am Pharm Assoc 2018;58:

87 CLOSING REMARKS / CONCLUSIONS Quitting smoking has immediate as well as long term benefits Medication(s) + behavioral counseling is the most effective approach Behavioral counseling: one on one counseling, quitline, group program, web based program Medications/ENDS: Highest quit rates observed with varenicline OR combination NRT Efficacy and safety well established, compared to risks of smoking Currently, evidence is insufficient to recommend ENDS for tobacco cessation Pharmacy based interventions are effective for cessation Brief interventions are effective, when time or expertise are limited Legislative advances provide pharmacists with prescriptive authority

88 Assessment Question #1 Ms. Lee, 67 yrs, requests help in selecting a medication for quitting. She currently smokes 20 cigarettes per day; the first one within 10 minutes of waking. She has dentures and is allergic to bandage adhesives (rash). Other medical problems include hypertension and eczema. She has never tried to quit before and likes the idea of an OTC nicotine replacement therapy product. Which of the following regimens is most appropriate during the first month of treatment? A. Nicotine patch 21 mg daily B. Nicotine gum 2 mg, 1 piece every 1 2 hours while awake C. Nicotine lozenge 4 mg, 1 piece every 1 2 hours while awake D. Nicotine inhaler, 1 cartridge every 1 2 hours while awake

89 Assessment Question #2 Which of the following statements is TRUE regarding electronic nicotine delivery systems (ENDS; e.g., e cigarettes)? A. ENDS are a safe alternative to cigarette smoking B. ENDS have lower exposure to carcinogens and toxins than tobacco smoke C. ENDS have a lower risk for nicotine dependence D. ENDS are more effective for cessation than nicotine replacement therapy

90 Assessment Question #3 Which of the following is TRUE based on outcomes of the FDA mandated EAGLES study? A. Combination nicotine replacement therapy was more effective than patch monotherapy for smoking cessation B. The boxed warning was removed from varenicline and bupropion SR for smoking cessation C. The placebo arm of the trial exhibited a significantly lower incidence of moderateto severe neuropsychiatric side effects than participants receiving bupropion SR or varenicline D. Participants with a mental health diagnosis had similar rates of neuropsychiatric events when compared to participants without a mental health diagnosis

91 Assessment Question #4 Which of the following is TRUE regarding the role of pharmacists in treating tobacco use and dependence? A. All states with prescriptive authority for tobacco cessation require pharmacists to complete relevant training. B. California was the first state to permit pharmacists to prescribe prescription medications for smoking cessation. C. Six month quit rates are 5 10% for patients who receive assistance from a pharmacist for quitting. D. Brief interventions are effective in helping patients quit.

92 QUESTIONS? Robin Corelli Karen Hudmon Annual Meeting & Exposition Seattle, Washington March 22 25