Nicotine Replacement Therapy Bupropion SR Nicotine Nasal Spray MOA - PDF document

9/28/15 ¡ Learning Objectives ¨ Given a patient scenario, identify appropriate TOBACCO CESSATION: pharmacological smoking cessation aids INCORPORATING MOTIVATIONAL INTERVIEWING AND EXAMINING THE ¨ Discuss the efficacy and safety of E-cigarettes ROLE OF E-CIGS in the literature ¨ Apply the spirit of motivational interviewing to Cheyenne Newsome, PharmD patient interactions PGY2 Ambulatory Care Resident University of New Mexico College of Pharmacy Nicotine Replacement Products FDA Approved Tobacco Cessation Therapies ¨ Nicotine Replacement Therapy ¨ Nicotine Patch ¤ Dose ¤ OTC: patch, gum, lozenge n 21mg/day patch if >10 cigarettes per day ¤ Rx only: inhaler, nasal spray n 14mg patch if <10 cigarettes per day or <45 kg ¨ Varenicline ¤ Counseling ¨ Bupropion SR n Apply on hairless area, rotate sites n May remove before bed if vivid dreams occur n Do not cut patch Nicotine Replacement Products Nicotine Replacement Therapy ¨ Nicotine Gum ¨ Nicotine Inhaler ¤ 2mg if smoke < 25 cigarettes/day ¤ Inhale deeply into the ¤ 4mg if smoke > 25 cigarettes/day back of throat or puff in ¤ 1 piece Q1-2 hours, NTE 24 pieces/day short breaths ¤ Chew and park method ¤ Initial dosing: ¨ Nicotine Lozenge n 6-16 cartridges per day ¤ 2mg smoke > 30 minutes of wakening ¤ 1 cartridge =2 cigarettes ¤ 4mg smoke within 30 minutes of wakening ¤ 1 lozenge Q1-2 hours, NTE 20 lozenges/day ¤ Rotate lozenge around mouth to decrease irritation Nicotrol Inhaler [prescribing information]. New York, NY: Pfizer Inc; 2008. 1 ¡

9/28/15 ¡ Nicotine Replacement Therapy Bupropion SR ¨ Nicotine Nasal Spray ¨ MOA ¤ Block reuptake of dopamine and norepinephrine ¤ 10mg/mL, 10 mL (200 sprays/unit) ¨ Dosing ¤ Each spray delivers 0.5mg nicotine ¤ Initiate at least 1 week before quit date ¤ Initial dose is 1-2 sprays IEN per hour ¤ 150mg x 3days, then 150mg BID thereafter ¤ NTE 80 sprays/24 hours ¤ Take in AM and early afternoon to reduce insomnia ¤ Prime before first use and if not used >24 hours ¨ Contraindicated in patients with seizure or eating ¤ Nasal irritation: 94% at 2 days, 81% at 3 weeks disorder ¨ Can delay or lessen weight gain Nicotrol Nasal Spray [prescribing information]. New York, NY: Pfizer Inc; 2010. Varenicline Varenicline- Conflicting Psychiatric ADEs ¨ MOA: ¨ FDA Adverse Event Reporting System from 1998 to ¤ Partial agonist of nicotinic acetylcholine receptor 2010 identified 3249 of suicidal behavoir +/- ¨ Dosing: depression in patients treated for smoking cessation ¤ Initiate 7-35 days before quit date ¤ 90% of events associated with varenicline ¤ 0.5mgx3 days, 0.5mg BIDx4 days, then 1mg BID ¨ Meta Analysis of 39 RCTs (10,761patients) found thereafter no evidence of increased risk of suicide attempt, ¨ Can minimize nausea by taking with food and a full suicidal ideation, depression, or death glass of water ¤ Varenicline was associated with an increased risk of ¨ Can cause vivid nightmares sleep disorders (OR 1.63) and abnormal dreams (OR ¨ Concerns in psychiatric conditions and 2.38) cardiovascular disease FDA Drug Safety Newsletter 2009; 2:1. Thomas KH et al. BMJ . 2015. 350:h1109. Varenicline- Concerns in CVD RCT of Comparative Efficacy ¨ Trial of 700 patients with stable CVD ¨ Population: 1504 adult smokers motivated to quit ¤ Patients treated with varenicline had numerically more ¨ Intervention: randomized to 1 of 6 treatments non-fatal MI (2 vs 0.9%) and need for coronary ¤ 1. nicotine lozenge revasculartization (0.6 vs 1.4%) ¤ 2. nicotine patch ¨ Nationwide cohort study in Denmark ¤ 3. bupropion SR ¤ 35,852 patients on varenicline or bupropion ¤ 4. nicotine patch +lozenge ¤ 57 MACE in varenicline vs 60 in buproprion (HR 0.96 CI ¤ 5. bupropion +nicotine lozenge 0.67-1.39) ¤ 6. placebo ¤ Subgroup analysis of patients with PMH CVD did not ¨ Outcome: Tobacco abstinence at 1 week, 8 weeks, significantly differ (HR 1.24 CI 0.72-2.12) and 6 months Rigotti NA. Circulation . 2010; 121(2) :221-9. Svanstrom H. BMJ . 2012;345:e7176. Piper ME et al. Arch Gen Psychiatry. 2009;66(11):1253-62 2 ¡

9/28/15 ¡ RCT of Comparative Efficacy Patient Case 1 ¨ Results: Abstinence at 6 months (OR vs placebo) ¨ 59 year old female Odds Ratio P-value ¨ PMH: diabetes, MI in 2007 s/p stent Lozenge 1.76 0.01 ¨ Meds: metoprolol, lisinopril, insulin glargine, Patch 1.83 0.006 aspirin Patch +lozenge 2.34 <0.01 ¨ Social hx: smoking 1 ppd x30 years Bupropion 1.63 0.025 Bupropion +lozenge 1.74 0.011 ¨ Presents to the pharmacy expressing interest in ¨ Combination NRT more effective than monotherapy tobacco cessation, wondering what options are NRT Piper ME et al. Arch Gen Psychiatry. 2009;66(11):1253-62 Patient Case 1 Patient Case 1 ¨ Questions for patient: ¨ Options: ¤ What has she tried in the past? ¤ NRT ¤ Does she have any dental work? n Combination of long and short acting ¤ Does she have any psychiatric conditions? ¤ Bupropion ¤ Other medications? ¤ Varenicline n Likely safe as patient has stable CVD n Benefits outweigh risks Requirements Requirements for Pharmacists Prescribing ¨ Complete training course approved by NMBOP Tobacco Cessation Therapy ¨ 0.2 CEU of live ACPE tobacco cessation therapy every 2 years New Mexico Pharmacy Rules and Laws ¨ Prescriptive authority for FDA approved tobacco 16.19.26 cessation drug therapy ¤ Both prescription and OTC ¨ Obtain informed consent from patient ¨ Pharmacist inform PCP of tobacco cessation therapy 3 ¡

9/28/15 ¡ Origin of E-cigs Electronic Cigarettes Patterns of E-cig Use E-cig Device and Use Adults (multimodal) Adults (web) High School Students Middle School Students 16 Percentage of e-cig ever use 14 12 10 8 6 4 2 0 2010 2011 2012 2013 2014 King BA et al. Nicotine Tob Res. 2015; 17:219. McMillen RC et al. Nicotine Tob Res. 2014. Arrazola RA et al. Morb Mortal Wkly Rep 2015; 64:381. UPToDate. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep 2013; 62:729. Potential Benefit ¨ Reduce prevalence of tobacco use as a tobacco cessation aid Benefits and Risks of E-cigs 4 ¡

9/28/15 ¡ Benefit: E-Cig for Smoking Cessation Benefit: E-Cig for Smoking Cessation ¨ Population: ¨ Results: ¤ 657 adult smokers motivated to quit Abstinence Rates at 6 months Nicotine E-cig: 7.3% ¨ Intervention: 4:4:1 randomization to Nicotine Patches: 5.8% ¤ 16mg nicotine e-cigarette Nicotine free E-cig: 4.1% ¤ 21mg/day nicotine patch ¤ Nicotine free e-cigarette ¨ Outcome: ¤ Biochemically verified abstinence at 6 months Bullen C et al. Lancet . 2013;382(9905):1629-37 Bullen C et al. Lancet . 2013;382(9905):1629-37 Potential Harms Harm: E-cig use in Adolescents ¨ E-cig use in adolescents ¨ Study found use of electronic cigarettes significantly increased likelihood of initiation of ¨ Accidental Ingestion combustible tobacco smoking (25.2% vs 9.3%) ¨ Health effects of vapor ¨ Evidence suggests nicotine exposure during adolescence may have lasting consequences on brain development ¨ Potential to renormalize combustible cigarettes Leventhal AM et al. AMA. 2015 Aug 18;314(7):700-7. US Department of HHS. Atlanta (GA): Centers for Disease Control and Prevention (US); 2014. Harm: Accidental Ingestion Harm: Safety of Vapor Exposure ¨ There is no data examining long-term effects of e-cigarettes ¨ Some reports have identified carcinogenic compounds in e-cigarettes ¨ Pulmonary effects of inhaling propylene glycol or glycerin are unknown Cheng T. Tob Control . 2014;23 (Suppl 2):ii2-ii17. CDC. Morbidity and Mortality Weekly Report 5 ¡

9/28/15 ¡ E-cig Federal Regulations E-cig State Regulations ¨ April 2014 ¨ April 2015 ¤ Sale of e-cigarettes ¤ FDA proposed to extend tobacco and nicotine cartridges authority to E-cigs to minors prohibited in ¤ If passed, would require E-cigarettes to: New Mexico n Register with FDA and report product ¤ Requires nicotine ingredients cartridges to be sold n Requirements to include health warnings in child resistant n Only market products after FDA review packaging US Preventative Task Force Summary of E-cigs ¨ September 2015 ¨ Not regulated by FDA ¨ Consensus is that e-cigarettes are likely safer ¤ Current evidence is insufficient to than combustible tobacco products recommend e-cigs for tobacco cessation in adults ¨ Long term health risks still not known ¤ Recommend clinicians direct patients who ¨ Encourage patients on their interest in smoking smoke tobacco to other cessation cessation interventions with established effectivenes ¨ Recommend FDA approved agent for smoking and safety. cessation therapy Origin of Motivational Interviewing Motivational Interviewing William R. Miller Professor of Psychology and Psychiatry at UNM since 1976 6 ¡