Pharmacologic Therapy for Tobacco Use & Dependence Nicotine Replacement Therapy (NRT) and Bupropion

Transcription

1 Pharmacologic Therapy for Tobacco Use & Dependence Nicotine Replacement Therapy (NRT) and Bupropion Jennifer Bluem Moran, MA, TTS Mayo Clinic Nicotine Dependence Center Rochester, MN 2013 MFMER slide-1

2 Learning Objectives Understand the evidence for expanded NRT dose ranges and combinations Develop detailed understanding of the side effects and important interactions of the NRT and bupropion Understand the most effective use of NRT and bupropion, and considerations in selected special populations Apply knowledge to patient cases 2013 MFMER slide-2

3 Pharmacologic Therapy for Tobacco Dependence Background Review specific medications NRT (patch and combinations) Bupropion SR Treatment of special populations 2013 MFMER slide-3

4 Trends in smoking prevalence MEN WOMEN % MFMER slide-4

5 MFMER slide-5

6 US smoking prevalence MFMER slide-6

7 Effectiveness and Abstinence Rates Compared With Placebo or Nicotine Patch at 6-Months Medication Arms Estimated abstinence rate (95% CI) Estimated OR vs Placebo (95% CI) Estimated OR vs Nicotine patch* (95% CI) Monotherapies Varenicline (2 mg/d) ( ) 3.1 ( ) 1.6 ( ) Nicotine nasal spray ( ) 2.3 ( ) 1.2 ( ) High-dose nicotine patch (>25 mg) (includes both standard or long-term duration) ( ) 2.3 ( ) 1.2 ( ) Long-term nicotine gum (>14 weeks) ( ) 2.2 ( ) 1.2 ( ) Varenicline (1 mg/d) ( ) 2.1 ( ) 1.1 ( ) Nicotine inhaler ( ) 2.1 ( ) 1.1 ( ) Bupropion SR ( ) 2.0 ( ) 1.0 ( ) Nicotine patch (6-14 weeks) ( ) 1.9 ( ) 1.0 Long-term nicotine patch (>14 weeks) ( ) 1.9 ( ) 1.0 ( ) Nortriptyline ( ) 1.8 ( ) 0.9 ( ) Nicotine gum (6-14 weeks) ( ) 1.5 ( ) 0.8 ( ) * Quit rates can double with medications 2013 MFMER slide-7

8 Relapse after cessation % abstinent weeks 2013 MFMER slide-8

9 Hardening through comorbidity As smoking prevalence falls the percent of smokers with Serious psychiatric disease Alcohol abuse Other drug abuse steadily rises 2013 MFMER slide-9

10 What new drug treatment approaches to try? Alternative dosing strategies Combination treatment using first-line medications Novel therapies 2013 MFMER slide-10

11 2013 MFMER slide-11

12 Optimizing Pharmacotherapy Goals of treatment Withdrawal symptom relief Control of cravings/urges Abstinence Modification of medication doses may be necessary to achieve these targets Higher doses Multi-drug regimens Longer course of treatment 2013 MFMER slide-12

13 Withdrawal Symptoms Depressed mood Insomnia Irritability, frustration or anger Anxiety Difficulty concentrating Restlessness Shakiness Increased appetite or weight gain American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.) 2013 MFMER slide-13

14 Nicotine Replacement Expanded treatment options 2013 MFMER slide-14

15 Nicotine Patch Standard: 21mg for 6 weeks, 14mg for 4 weeks, 7mg for 2 weeks Evidence for tapering or length of therapy is minimal Dose ranging studies suggest 50% of smokers are inadequately treated in this fashion 2013 MFMER slide-15

16 Dale, et al. JAMA, MFMER slide-16

17 Findings from Dose Ranging Study: Dose associated with 8 weeks (P =.007; OR 2.5; 95% CI: ) 8 weeks 6 months 1 year 11 mg 59% 59% 41% 22 mg 62% 54% 35% 44 mg 100% 78% 67% Dale, et al. JAMA, MFMER slide-17

18 Dose-effect of hi-dose NP Percent point-prevalence abstinent mg/d X 4 wks 44 mg/d X 4 wks 22 mg/d X 4 wks m/d X 4 wks NP22 NP44 0 EOT-1 EOT-2 26WKS 8 weeks of blinded therapy Jorenby, et al. JAMA 1995;274: MFMER slide-18

19 Higher Dose Nicotine Patch There is a dose-response effect Long-term abstinence improved; RR of 1.15 (95% CI: 1.01 to 1.30)* Treatment-related AE s are uncommon Withdrawal symptoms less with higher dose NRT *Cochrane Database of Systematic Reviews MFMER slide-19

20 Percentage Replacement Case Case example 52 yo accountant who smokes CPD Baseline cotinine = 293 ng/ml What nicotine patch dose would you advise? 2013 MFMER slide-20

21 Percentage Replacement Case Received NP 42mg/day Steady state cotinine= 292 ng/ml Percent replacement= 100% 2013 MFMER slide-21

22 Patch Dosing 40 cpd or greater = 42 mg/day cpd = mg/day cpd = mg/day 10 cpd or less = 14 mg/day * If a dose >42 mg/day may be indicated, contact the patient s prescriber 2013 MFMER slide-22

23 Patch Dosing Schedule Use initial dose for 4-6 weeks After 4-6 weeks of smoking abstinence, taper 7-14mg steps every 2-4 wks Length of therapy varies based on patient response Withdrawal symptoms while tapering are mild to nonexistent Advise using overnight 2013 MFMER slide-23

24 Length of Therapy Optimal length of treatment not established for most NRT Patients and providers under-treat Minimum 8 weeks Evidence supports 6 months or more Rationale: reduce relapse, harm reduction Risk: dependence, long-term side effects 2013 MFMER slide-24

25 Adherence to NRT Treatment Balmford J, et al. Nicotine & Tobacco Research 2011;13: Only 28.6% of NRT users completed the recommended 8 weeks of treatment Most quit prematurely because they believed the medication was not working, had unwanted side effects or believed that they no longer needed treatment MFMER slide-25

26 Nicotine Patch 8 wk vs. 24 wk Treatment Schnoll R A et al. Ann Intern Med 2010;152: MFMER slide-26

27 2013 MFMER slide-27

28 Combination NRT Nicotine patch plus immediate release NRT 2013 MFMER slide-28

29 Combination NRT rationale Combine long-acting patch with ad libitum short-acting medication (gum, lozenge, inhaler, nasal spray) Encourages patient to be in control of cravings and withdrawal symptoms, while keeping a consistent baseline Improves compliance with treatment plan Achieves higher drug concentrations Allows further dose adjustments Replace tactile stimulus by mimicking smoking 2013 MFMER slide-29

30 Medication: Effects Stop on Date Withdrawal & Urges Intensity Without Medication Intensity With Medication TIME 2013 MFMER slide-30

31 Immediate-release NRTs Nicotine gum, lozenge and inhaler Buccal mucosal absorption Affected by ph Technique important with NG, NL Peak absorption in min. Nicotine nasal spray peak absorption in 5-10 min MFMER slide-31

32 2013 MFMER slide-32

33 Smoking produces much higher nicotine levels and much more rapidly than NRT Increase in nicotine concentration ( ng/ml ) Cigarette Gum 4 mg Gum 2 mg Patch 42 mg Inhaler Nasal spray Patch 21 mg Minutes Source: Balfour DJ & Fagerström KO. Pharmacol Ther : MFMER slide-33

34 Nicotine Gum OTC: 2 mg and 4 mg Regular, Mint, Orange, other flavors Chew and Park Avoid acidic beverages Monotherapy: 10-15/day initially; use 4 mg if first cig. in a.m. is within 30 min. Most often used in combination with other NRT 2013 MFMER slide-34

35 Nicotine Lozenge OTC: 2 mg and 4 mg Regular, Mini, Mint, Cherry, other flavors Dissolves in mouth over minutes Avoid acidic beverages Not to be chewed or swallowed whole Delivers 25% more nicotine than the gum 2013 MFMER slide-35

36 Nicotine Lozenge and Gum Dosing Based on time to first cigarette < 30 minutes = 4 mg > 30 minutes = 2 mg Based on cpd >20 cpd = 4 mg <20 cpd = 2 mg Monotherapy: 1-2 pieces every 1-2 hours Minimum of 9 lozenge/day or gum/day Taper over 12 weeks (or as tolerated) Consider in Combination with other NRT (Use 2 mg lozenge or gum) 2013 MFMER slide-36

37 Nicotine Nasal Spray 1 dose = 1 spray in each nostril Starting dose: 1 dose 1-2 times/hr, Up to 5 times/hr or 40 times/day Most average doses/day initially Length of Rx: 12 weeks but can be shorter Can taper or stop abruptly, as tolerated 2013 MFMER slide-37

38 Nicotine Nasal Spray Side Effects - moderate to severe nasal irritation (81-94%) nasal congestion transient change in sense of smell/taste Dependency profile between other NRT and cigarettes Contraindication - severe reactive airway disease 2013 MFMER slide-38

39 Nicotine Inhaler Porous plug saturated with nicotine Delivers vaporized nicotine to oral cavity--not the lungs Average nicotine level = 6.3 ng/ml (29% replacement) Provides withdrawal symptom relief 2013 MFMER slide-39

40 Nicotine Inhaler Dose Instruction Puff on inhaler several times a minute Each cartridge will last about 30 minutes of active puffing 1 cartridge = as much nicotine as 2-3 cigarettes Monotherapy: At least 6 cartridges each day, up to 16/day Can be used alone or in combination with other NRT 2013 MFMER slide-40

41 Nicotine Inhaler: Side Effects local irritation throat/mouth (40%) coughing (32%) rhinitis (23%) puff not inhale 2013 MFMER slide-41

42 Combination NRT Compared With Single Agent NRT Nicotine patch + short-acting NRT Patch provides steady baseline NG, NL NNS, NI respond to urges Withdrawal may be improved Overall abstinence rates at 6 mos. better OR 1.35 (95% CI )* *Cochrane Database of Systematic Reviews MFMER slide-42

43 COMBINATION THERAPY RCT of 1504 smokers in a research clinic Received 1 of 6 treatments for 8 weeks 6 brief counseling sessions 7-day point prevalence abstinence at 8 wks and 6 months Piper M, et al. Arch Gen Psychiat 2009;66: MFMER slide-43

44 COMBINATION THERAPY RCT of 1346 smokers recruited from 12 primary care clinics in Wisconsin Received 1 of 5 active treatments for 8 weeks Referred for counseling via telephone quitline 7-day point prevalence at 8 wks and 6 months Smith SS, et al. Arch Intern Med 2009;169: MFMER slide-44

45 TRIPLE COMBINATION THERAPY Steinberg MB, et al. Annals Intern Med 2009; 150: RCT of 127 smokers with known CVD, COPD, cancer, diabetes Compared triple combination (patch + bupropion + nicotine inhaler) to patch alone; no placebo treatment Triple therapy stopped based on symptoms (mean treatment duration 89 days); patch alone to taper and stop after 10 weeks (mean treatment duration 35 days) At 6 months 7 day point prevalence abstinence: Triple Rx 35% Patch 19% (OR 2.57, 95% CI 1.05 to 6.32, p-value 0.04) 2013 MFMER slide-45

46 How to use Combination Rx Use NP at dose adjusted for CPD Assess patient preference for immediaterelease NRT Use IR NRT scheduled or ad lib Every 1-2 hours while awake In response to urges to smoke Taper NP as usual Taper IR NRT after 12 weeks 2013 MFMER slide-46

47 Bupropion SR Wellbutrin Zyban 2013 MFMER slide-47

48 Mechanism of Action Blocks reuptake of NE and DA Increased DA in the mesolimbic reward center mimics nicotine Uncertain of NE role in smoking cessation May act as a nicotinic receptor blocker 2013 MFMER slide-48

49 Bupropion SR (Zyban) Point-prevalence smoking cessation (%) (Placebo vs 150 mg and 300 mg p<0.02 at all points) Placebo 100 mg 150 mg 300 mg 0 6 wk 12 wk 24 wk 52 wk 2013 MFMER slide-49

50 Bupropion: Relapse prevention Point-prevalence abstinence (%) Time(wk) 12* 24* 52* 104 Placebo mg *p<0.05 for placebo vs active 2013 MFMER slide-50

51 Weight Gain in Abstainers Time (wk) bupropion control p<0.05 at all times (weight in kg) 2013 MFMER slide-51

52 Bupropion SR prescribing Set target quit date 1 week from start of medication Begin with 150 mg daily for 3 days Increase to 150 mg twice daily at least 8 hrs apart Evening dose before 6PM Treat for 8-52 weeks 2013 MFMER slide-52

53 Common adverse events reported in 40 controlled clinical trials of bupropion SR AE Mean % Range Studies Insomnia 32.3 (10 to 53) 25 Dry mouth 23.9 (6 to62) 17 Headache 21.5 (6 to 56) 9 Diarrhea 17.5 (6 to 50) 5 Anxiety 20.3 (10 to 31) 4 Nausea 19.8 (10 to 44) MFMER slide-53

54 Serious adverse effects with bupropion SR Seizure rate about 1/1000 treated 7/6409 subjects on active therapy in RCT s Post marketing studies show seizures in people with known predisposition Contraindications: known seizure (ever); structural brain abnormality; serious closed head injury Hypersensitivity (about 1%) Hives, urticaria, angioedema Neuropsychiatric symptoms 2013 MFMER slide-54

55 Bupropion: Seizure Screen Known seizure history: epilepsy, febrile seizure, withdrawal seizure Structural brain lesion: tumor, stroke, previous brain surgery Drugs that lower seizure threshold: phenothiazines, benzodiazepines, theophyline, ethanol Anorexia/Bulimia Significant head trauma: prolonged LOC, skull fracture, intracranial bleeding 2013 MFMER slide-55

56 Bupropion: Boxed Warning (July 2009) Serious neuropsychiatric events, including depression, suicidal ideation, suicide attempt, and completed suicide, have been reported in patients with and without pre-existing psychiatric disease who were taking bupropion for smoking cessation; some experienced worsening of their psychiatric illnesses. All patients should be observed for changes in behavior, hostility, agitation, depressed mood, and suiciderelated events, including ideation, behavior, and attempted suicide. The patient should stop taking bupropion and contact a healthcare provider immediately if any neuropsychiatric behavior that is not typical for the patient is observed, or if the patient develops suicidal ideation or suicidal behavior. This risk should be weighed against the benefits of its use MFMER slide-56

57 Bupropion/Patch Combination Abstinence at 12 mos Placebo 15.6% NP alone 16.4% Bupropion 30.3% Bupropion plus NP 35.5% 2013 MFMER slide-57

58 Bupropion SR plus Patch Begin NP on quit date Match NP dose to CPD or cotinine Begin bupropion 1 week prior to quit date Ramp up bupropion from 150mg to 300mg per day after 3 days Treatment duration based on patient response Often weeks ± Combination with NRT 2013 MFMER slide-58

59 Nicotine replacement and CVD Joseph,et al NEJM 1996;335: subjects with CVD (8 women) RCT of nicotine patch for 10 wks Primary end points (14 wks f/u) Death, MI, arrest Hospitalized for increased CVD Secondary end points 2013 MFMER slide-59

60 Nicotine replacement and CVD Joseph, et al study results... End point NRT PBO Primary: 5.4 % 7.9% Secondary: 11.9% 9.7% Total : 16.3% 16.2% Death(no.): MFMER slide-60

61 Smoking and Pregnancy Counsel regarding risks to self and developing fetus Pharmacologic treatment if needed NRT pregnancy category D Bupropion SR is category C Postpartum relapse common Stress continuing benefits to infant and mother 2013 MFMER slide-61

62 Drug Risks in Pregnancy C :Animal studies have shown significant adverse fetal effects, but no controlled studies are available in women D :Positive evidence of human fetal risk exists, but benefits in certain situations may make use acceptable despite risks 2013 MFMER slide-62

63 Tobacco dependence treatment in pregnancy Recommendation: Because of the serious risks of smoking to the pregnant smoker and the fetus, whenever possible pregnant smokers should be offered person-to-person psychosocial interventions that exceed minimal advice to quit. (Strength of Evidence = A) Recommendation: Although abstinence early in pregnancy will produce the greatest benefits to the fetus and expectant mother, quitting at any point in pregnancy can yield benefits. Therefore, clinicians should offer effective tobacco dependence interventions to pregnant smokers at the first prenatal visit as well as throughout the course of pregnancy. (Strength of Evidence = B) 2013 MFMER slide-63

64 Tobacco dependence treatment in pregnancy For women who are not able to quit successfully with behavioral treatment alone Short acting oral NRT ad lib Nicotine patch in lowest effective dose if oral NRT is ineffective Combination NRT if needed Bupropion alone or added to NRT if needed No data on varenicline safety 2013 MFMER slide-64

65 Varenicline Chantix 2013 MFMER slide-65

66 Abstinence: The Effects of Treatment* Spontaneous 1-2% Advice to quit 3-5% Advice plus NRT 6-12% Counseling + Rx# 15-20% Clinical trials 20-25% Residential treatment 45-50% * 12 month abstinence rates; # Rx= tailored pharmacotherapy 2013 MFMER slide-66

67 History of Pharmacotherapy Nicotine polacrilex (gum) 1982 Nicotine patch 1992 Nicotine patch and gum OTC 1996 Bupropion SR 1997 Nicotine lozenge OTC 2002 Varenicline MFMER slide-67

68 Need for New Therapy Long-term abstinence disappointingly low Current therapy available years New therapeutic options may motivate hardened smokers New therapeutic targets to be exploited 2013 MFMER slide-68

69 Varenicline Mode of Action: Partial Agonist α4β2 nach receptor To provide relief from craving and withdrawal agonist effect Block satisfaction and rewarding effects of nicotine antagonist effect Coe JW, et.al. J Med Chem. 2005;48:

70 The nachr Pentameric receptors throughout the brain and composed of alpha and beta subunits Highest concentration of nachr s is in the mesolimbic dopaminergic system ( reward center ) The high affinity nachr is the α4β2 Stimulation of the α4β2 nachr causes DA release in the reward center 2013 MFMER slide-70

71 Varenicline Mechanism of Action Varenicline targets the nicotinic acetylcholine receptor (nachr) in a unique fashion Partial agonist with specificity for the high-affininty α4β2 nachr Agonist -- stimulates the receptor to decrease craving and withdrawal Antagonist blocks the receptor to decrease the reinforcement associated with smoking No clinically relevant drug-drug interactions NH N N 2013 MFMER slide-71

72 Varenicline Dosing Taken with full glass of water after eating Start one week prior to Target Quit Date Days 1-3: 0.5 mg once daily Days 4-7: 0.5 mg twice a day (morning and evening) Day 8 and for 11 weeks: 1.0 mg twice daily If abstinent at 12 weeks, continue twice daily for an additional 12 weeks 2013 MFMER slide-72

73 Precautions Renal Failure Severe (CrCl < 30 ml/min): 0.5 mg twice daily Hemodialysis patients: 0.5 mg daily Pregnancy: Not recommended Lactation: Not recommended Adolescents: Untested 2013 MFMER slide-73

74 Conclusions from Varenicline Phase 2 Trials Most efficacious dose is 1 mg twice daily There is a dose response from 0.5 mg per day to 2 mg per day Initial dose titration (ramp-up) reduces nausea compared with non-titration Self-titration may be an alternative to fixed dose approach 2013 MFMER slide-74

75 Varenicline for Relapse Prevention Smokers who have risk factors for relapse Heavier smokers Other smokers in household Comorbid mental health conditions Past substance abuse Late quitters (smokers quitting well after their target quit date) 2013 MFMER slide-75

76 Varenicline Prescribing and Safety 2013 MFMER slide-76

77 Common Adverse Events in Clinical Trials (%) Varenicline Placebo Nausea Insomnia Abnl dreams Headache Other GI Discontinued MFMER slide-77

78 Varenicline: FDA Warning 2008 All patients being treated with Chantix should be observed for neuropsychiatric symptoms including changes in behavior, agitation, depressed mood, suicidal ideation, and suicidal behavior. These symptoms, as well as worsening of pre-existing psychiatric illness, have been reported in patients attempting to quit smoking while taking Chantix 2013 MFMER slide-78

79 Serious neuropsychiatric events, including, but not limited to depression, suicidal ideation, suicide attempt and completed suicide have been reported in patients taking Chantix. These events have occurred in patients with and without pre-existing psychiatric disease. Advise patients and caregivers that patients should stop taking Chantix and contact a healthcare provider immediately if agitation, hostility, depressed mood, or changes in behavior or thinking that are not typical for the patient are observed, or if the patient develops suicidal ideation or suicidal behavior MFMER slide-79

80 The risks of Chantix should be weighed against the benefits of its use. Chantix has been demonstrated to increase the likelihood of abstinence from smoking for as long as one year compared to treatment with placebo. The health benefits of quitting smoking are immediate and substantial MFMER slide-80

81 Varenicline Boxed Warning The risk of serious adverse events while taking these products [Chantix and Zyban] must be weighed against the significant health benefits of quitting smoking. Smoking is the leading cause of preventable disease, disability, and death in the United States and we know these products are effective aids in helping people quit. Janet Woodcock, M.D. Director FDA Center for Drug Evaluation and Research Press release, July 1, MFMER slide-81

82 Varenicline and Neuropsychiatric Symptoms Advise patients and family members that this has been observed Ask patients and/or family to report any symptoms like this to you Patients with serious psychiatric comorbidity were not included in clinical trials No cause and effect relationship has been established 2013 MFMER slide-82

83 Varenicline and Cardiovascular Serious Adverse Events (SAE) Overall CV SAE rates: Varenicline 52/4908 (1.06%) Placebo 27/3308 (0.82%) Peto OR 1.72 (95% CI 1.09 to 2.71) Rigotti et al Overall Singh S, et al. Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. CMAJ 2011 [July 4]. doi: /cmaj MFMER slide-83

84 Varenicline and Cardiovascular Serious Adverse Events (SAE) Hays JT. Varenicline for smoking cessation: is it a heartbreaker? CMAJ 2011 [July 4].doi: /cmaj Problems with the Singh et al (CMAJ 2011) meta-analysis Cardiovascular SAE s were rare in both groups Only 0.82% placebo, and 1.06% varenicline Absolute difference 0.24% Greater numbers lost to follow-up in placebo arms Lost opportunity to count CV events in placebo subjects Bias in favor of fewer CV events ascertained in placebo arms No adjudication of CV events in all but one study The only clinical trial of varenicline efficacy among subjects with known CVD raised no safety concerns (Rigotti et al. Circulation 2010;121: ) 2013 MFMER slide-84

85 Varenicline and cardiovascular risk Hays JT. Varenicline for smoking cessation: is it a heartbreaker? CMAJ 2011 [July 4].doi: /cmaj MFMER slide-85

86 Additional Prescribing Information No dose reduction needed in Geriatric population Patients with liver disease No important drug-drug interactions Reduce dose in renal impairment Estimated creatinine clearance <30 ml/min reduce dose to 0.5 mg daily and titrate to 0.5 mg BID as tolerated 2013 MFMER slide-86

87 Varenicline Prescribing Use in combination with behavioral treatment Start medication 1 week prior to target quit date Days 1-3, Varenicline 0.5mg daily Days 4-7, Varenicline 0.5mg twice daily Day 8 to end of treatment 1.0mg twice daily TQD on day 8 Take with food Dose reduction with severe renal impairment Supplied as starter card (11X0.5mg tabs) and 4-week packs of 1 mg BID or bottles of 56 Treat for 3 to 6 months 2013 MFMER slide-87

88 2 nd Line Medications 2013 MFMER slide-88

89 Nortriptyline 199 smokers Randomly assigned to active vs. placebo Nortriptyline and Cognitive Behavioral Therapy (CBT) vs. Control Nortriptyline 25 mg/d x 3, 50 mg/d x 4. Serum levels at week 2, dose to 75 mg/d or 100 mg/d if not therapeutic at week 2 only Nortriptyline continued for 12 weeks Continuous abstinence: Nortriptyline 24% vs. Placebo 12% Hall SM. Arch Gen Psych 55:683, 1998

90 Nortriptyline- 2nd line Side effects - sedation (may be hazardous when operating equipment) weight gain dry mouth (64-78%) blurred vision (16%) lightheadedness (49%) urinary retention shaky hands (23%) Caution in patients with cardiovascular disease as overdose may be cardiotoxic 2013 MFMER slide-90

91 Clonidine 2nd line Therapy Anti-hypertensive medication Available as pills or patches Five randomized controlled trials Mixed results Side effects significant Dry mouth Sedation Low blood pressure Must taper off of medication serious high blood pressure can result if stopped suddenly 2013 MFMER slide-91

92 Summary and Conclusions 2013 MFMER slide-92

93 Conclusions NRT Patch dosing matched to CPD is safe and effective Combined NRT s are efficacious Length of therapy guided by patient response (longer may be better) Safe in smokers with CHD May be safe in pregnant smokers 2013 MFMER slide-93

94 Conclusions Bupropion Safe and effective in most populations at 300mg per day Increased efficacy combined with NP Can be safely combined with SSRI s Attenuates post-cessation weight gain Safe in smokers with medical comorbidity May be safe in pregnancy 2013 MFMER slide-94

95 Conclusions Varenicline Varenicline is efficacious for the treatment of tobacco dependence Side effects have been generally mild and well-tolerated Trend in increased cessation with duration of use Varenicline is as effective as other first-line treatments for tobacco dependence Monitor patients for new neuropsychiatric symptoms while on therapy 2013 MFMER slide-95

96 Optimizing Pharmacotherapy 2012 MFMER slide-96

97 Bibliography Treating Tobacco Dependence in a Medical Setting, Richard D. Hurt, Jon O. Ebbert, J. Taylor Hays, and David D. McFadden CA Cancer J Clin 2009; 59; ; originally published online Aug Treatment of Tobacco Dependence MICHAEL V. BURKE, EDD; JON O. EBBERT, MD, MSC; AND J. TAYLOR HAYS, MD Mayo Clin Proc. 2004;83(4): MFMER slide-97