Smoking Cessation

Smoking Cessation Mark J. Chirico, Pharm. D. Assistant Clinical Professor AHEC Pharmacist University of Florida

Objectives  Appreciate the importance of smoking cessation based     

on population data. Recognize the health risks and financial burden of smoking. Realize that tobacco use is an addictive behavior similar to that of other drugs with high abuse potential. Learn the “5 A’s” associated with health-provider assisted smoking cessation. Become familiar with the various smoking cessation aids available by prescription and OTC. Obtain the clinical knowledge necessary to recommend smoking cessation aids and become confident in counseling patients on their use.

Epidemiology of Tobacco Use  Surgeon General’s Statement – 1982 “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.

Public Health Tasks  Focus on  Prevention  Teen smoking  Advertisement  Education  Accessibility  Cessation assistance  Health care providers  Insurers  Employers

US Cigarette Consumption > 18 yrs old1 4500 4000

per capita consumption

3000 2500 2000 1500 1000 500 0 19 00 19 10 19 20 19 30 19 40 19 50 19 60 19 70 19 80 19 90 20 00 20 04

# cigs/person/yr

3500

Year

STATE-SPECIFIC PREVALENCE of SMOKING among ADULTS, 2002 Illinoi s 22.9 %

Californi a 16.4% Nevada 26.0% Utah 12.7%

Kentuck y 32.6% New York 22.4%

Texas 22.9%

Florida 22.1 %

Centers for Disease Control and Prevention. MMWR 2004;52:1277–1280.

TRENDS in ADULT SMOKING, by SEX—U.S., 1955–2002 Trends in cigarette current smoking among persons aged 18 or older, by sex 60 50

22.5% of adults are current smokers

Male

Percent

40 30 20

Female

25.2% 20.0%

10 0

1955 1959 1963 1967 1971 1975 1979 1983 1987 1991 1995 1999 Year

70% want to quit Graph provided by the Centers for Disease Control and Prevention. 1955 Current Population Survey; 1965–2001 NHIS. Estimates since 1992 include some-day smoking.

Prevalence of Adult Smoking by Ethnic Group1 40

% Smokers

35

30

Native Amer/ Alaska Native

25

White Non-Hisp

20

Black Non-Hisp

15

Hispanic

10

Asian/ Pacific Isl

5

0

Ethnicity

Prevalence of Adult Smoking by Education1 50 45 40

% smoker

35 30 25 20 15 10 5 0

No HS diploma

GED

HS diploma

Some college

Under- Graduate grad degree degree

Smoking Cessation Among Adult Smokers by Gender1 60 50

%

40 30

Male Female

20 10 0 1965

1970

1975

1980

1985

1990

1995

2000

2003

Smoking Mortality  Smoking remains the leading preventable cause of death in the US  1 out of 5 deaths  438,000 deaths annually

 Projected death toll – end of 21st century  Expected to reach 1 billion total  100 million mark reached at the end of 1900’s

Economic Impact of Smoking  Medical expenditures  $75.5 billion

 Productivity  $ 82 billion

 Total cost (annual)  $ 157.5 billion

Health Risks  Cardiovascular disease  Lung disease (COPD)  Cancer  Sexual dysfunction  Osteoporosis  Delayed post-surgical healing  Periodontal disease

Health Risks of 2 -Hand Smoke nd

 SIDS  Asthma  Growth retardation (children)  Cancer  Cardiovascular disease  Otitis media (↑ incidence in children)

Health Benefits of Quitting  20 minutes - BP↓, HR↓  8 hours – Carbon monoxide ↓, O2 ↑ to normal levels  24 hours – Risk of heart attack ↓  48 hours – Nerve endings regenerate, sense of taste and smell return to normal

QUITTING: HEALTH BENEFITS2 Time Since Quit Date Circulation improves, Lung cilia regain normal walking becomes easier 2 weeks to function Lung function increases up to 30% Excess risk of CHD decreases to half that of a continuing smoker Lung cancer death rate drops to half that of a continuing smoker Risk of cancer of mouth, throat, esophagus, bladder, kidney, pancreas decrease

3 months

1 to 9 months

Ability to clear lungs of mucus increases Coughing, fatigue, shortness of breath decrease

1 year 5 years

Risk of stroke is reduced to that of people who have never smoked

after 15 years

Risk of CHD is similar to that of people who have never smoked

10 years

BENEFICIAL EFFECTS of QUITTING: PULMONARY EFFECTS FEV1 (% of value at age 25)

AT ANY AGE, there are benefits of quitting Never smoked or not susceptible to smoke

100

75 Stopped smoking at 45 (mild COPD)

Smoked regularly and susceptible to effects of smoke

50 Disability 25

Stopped smoking at 65 (severe COPD)

Death 0 25

50

75

Age (years) COPD = chronic obstructive pulmonary disease

Reprinted with permission. Fletcher & Peto. Br Med J 1977;1(6077):1645–1648.

Nicotine Addiction  1988 Surgeon General’s Report  Nicotine is the drug in tobacco that causes addiction  Tobacco addiction is similar to drug addiction, e.g heroin and cocaine

Fiore et al. Treating Tobacco and Dependence. Clinical Practice Guideline Rockville, MD: USDHHS, PHS, 2000.

Nicotine Kinetics  Absorbed in alkali environment (buccal membranes, pH = 7)  This accounts for nicotine absorption from chew, cigars, and pipe tobacco

 Tobacco smoke is absorbed in the lung (alveolar absorption, pH = 7.4) - reaches brain in 11 sec., crosses BBB - t½ = 2 hrs  Nicotine also absorbed well by dermal tissue

Nicotine Pharmacodynamics  CNS   

Pleasure (dopamine) Arousal (NE, Ach) Anxiolytic (endorphins, GABA)

 Circulatory    

↑ HR (10-20 bpm) ↑ CO ↑ BP(5-10 mmHg) Vasoconstriction (coronary and cutaneous)

“Dopamine Reward Pathway”  Stimulation of dopamine receptors in the brain results in pleasure  Reinforces repeated behavior

 Tolerance develops from up-regulation of nicotine receptors which results in increased consumption

Nicotine Withdrawal  Expressed as a result of abrupt discontinuation – fxn of absence of dopamine receptor stimulation  Peak @ 24-48 hrs  Dissipates after 2-4 weeks

 Symptoms    

Anger Irritability Anxiety Craving

Nicotine Withdrawal  Symptoms (cont.)   

Sleep disturbances ↓ concentration Impaired task performance

 Activates “Nicotine Addiction Cycle”

NICOTINE ADDICTION CYCLE

Reprinted with permission. Benowitz. Med Clin N Am 1992;2:415–437.

Factors Contributing to Tobacco Dependence  Environment  Conditioning (cues and triggers)  Social interaction (family, peers)

 Physiology  

Genetics Co-existing medical conditions (psychiatric)

 Pharmacology  Withdrawal  Weight control  Pleasure

Assisting Patients With Quitting  Behavioral intervention is just as important as drug treatment  Pharmacotherapy + Counseling > either alone  USPHS – June 2000  Published “Treating Tobacco Use and Dependence – Clinical Practice Guidelines”

The 5 A’s  Ask  Advise  Assess  Assist  Arrange

Ask  “Do you smoke or use other types of tobacco?”  Why?- it is important  Link to other co-existing diseases (HTN, CVD, Diabetes)  Link to possible drug-drug interactions

 Non-judgmental tone  Leads to withdrawal, incomplete disclosure

Advise  “It’s important to quit as soon as possible, and I can help.”  Emphasize that you have specialized training

 Be: Clear of intent Strong - “…as soon as possible…” Personalized – tie to current health status, family benefit (children, spouse, roommate), save $  Sensitive – recognize difficulty in quitting   

Assess  “When would you like to quit?”  Let patient establish a “quit date” (< 30 days)  Make an appointment between 1st visit and quit date

 Previous attempts to quit?  Scales and questionnaires  Fagerstrom Test for Nicotine Dependence  ↑score = ↑dependence Heatherton TF, Kozlozwski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991;86:1119-1127.

IS A PATIENT READY TO QUIT? Does the patient use tobacco? Yes

Is the patient now ready to quit? No

Promote motivation

No

Did the patient once use tobacco?

Yes

Yes

Provide treatment The 5 A’s

Prevent relapse*

No

Encourage continued abstinence

*Relapse prevention interventions not necessary if patient has not used tobacco for many years and is not at risk for re-initiation.

Fiore et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, 2000.

Assist  Not ready to quit  

Motivational intervention Repeat offers at future visits

 Ready to quit  Enroll in smoking cessation program

 Recently quit  Continued support

Assisting Patients With Quitting  Discuss key issues        

Motivation to quit Confidence in abiltiy to quit Triggers Routines associated with smoking Stress-related smoking Social support (family, friends) Weight gain Withdrawal

Assisting Patients With Quitting  Facilitate  Tobacco use log  Identifies smoking patterns and triggers  When and why  Pros & cons of different cessation methods  Coping strategies  Environmental control  Behavior modification

Assisting With Weight Gain  Average ↑ = 10 lbs.  Good eating habits  Discourage dieting while trying to quit  Recommend healthy snacks, sugarless gum

 Increase physical activity  Non-food rewards

Assisting With Withdrawal  Educate patient to recognize       

Anger, irritability Anxiety Cravings Restlessness Impatience Sleep disturbances Nervousness

Arrange  Follow-up care  In person or by phone  Verify phone #, cell, HIPPA

 Increased # of visits = higher success rate  First appointment – 1 week after quit date  Second appointment – 30 days or less  Depends on progress, pt needs

Quit Rate : Visit Ratio

2

Number of visits

% Quit Rate

0-1

12.4

2-3

16.3

4-8

20.9

>8

24.7

Methods For Quitting  Non-Pharmacologic “Cold turkey” Unassisted tapering  Lighter brand  ↓ allotment per day  Special filters or holders  Assisted tapering  LifeSign® - computerized schedule with telephone  

support

Methods For Quitting  Self-help programs  Massage therapy  Acupuncture  Hypnosis

Pharmacologic Methods For Quitting  Nicotine Replacement Therapy (NRT)  Gum, lozenge, patch, nasal spray, inhaler

 Psychotropics  Bupropion SR

 Partial nicotine agonist  Varenicline (Chantix®)

 Other  Clonidine, nortriptyline, etc.

Nicotine Replacement Therapy  Reduces intensity of physical withdrawal symptoms from nicotine  Allows patient to focus on behavioral and psychological aspects of smoking cessation  Beware: Nicotine replacement therapy can also be addicting!

Nicotine Replacement Therapy  Advantages No carcinogens or toxic agents Slower, lower, less variable nicotine levels Antagonizes the reinforcing action of repeated smoking  Delays weight gain   

Nicotine Replacement Therapy  Disadvantages  Cardiovascular  CI in post-MI (< 2 weeks), arrhythmias, unstable angina

 TMJ  Gum only  Pregnancy and lactation  Category D

Nicotine Replacement Products  Nicotine Gum (Nicorettte®, generics) OTC      

Nicotine polacrilex resin complex Sugar-free Buffered to ↑ buccal absorption Flavored (regular, mint, orange) Strengths – 2 mg, 4 mg Dose  > 25 cigs/day – 4 mg  < 25 cigs/day – 2 mg

Nicotine Gum  Peak effect – 30 min (cigs = 10 min)  Fixed dosing schedule  Weeks 1-6 – 1 pc. Q 1-2 hrs (9 pc./d, max 24)  Weeks 7-9 – 1 pc. Q 2-4 hrs  Weeks 10-12 – 1 pc. Q 4-8 hrs

 RCT’s – 50% higher success rate than placebo , 4 mg > 2 mg in heavy smokers

Nicotine Gum Patient Information  Place 1 piece of gum at a time in mouth  Chew slowly  Stop chewing at first sign of taste  Park between cheek and gum  Repeat prn (fades in ~ 30 min.)  Do not eat or drink for 15 min. before or while chewing gum. Coffee, cola, acidic juices, wine decrease absorption

Nicotine Gum ADR’s  Lightheadedness  Belching  Hiccups  Headache  GI upset  Jaw muscle ache

Nicotine Lozenge  Commit OTC  Nicotine polacrilex  25% more nicotine absorption than gum  Sugar-free  Mint flavored  Buffered  Strengths – 2 mg, 4 mg

Nicotine Lozenge  Dose – based on “Time to First Cigarette” (TTFC) after waking    

TTFC < 30 min – 4 mg TTFC > 30 min – 2 mg Max = 9pc./day Based in fixed schedule like gum

 RCT’s – 50% higher success rate than placebo

Nicotine Lozenge Patient Information  Place one lozenge at a time in mouth and allow     

to dissolve slowly Will experience warm, tingling sensation Switch lozenge from side to side Do not chew or swallow Effect will last 20-30 minutes Do not eat or drink for 15 min. before or while using. Coffee, cola, acidic juices, wine decrease absorption

Nicotine Patch  Nicoderm CQ, Nicotrol®, generics OTC  General composition   

Top layer - impermeable surface layer Middle layer – nicotine reservoir Bottom layer (closest to skin) – adhesive layer

 Nicotine absorption via skin avoids 1st pass metabolism

TRANSDERMAL NICOTINE PATCH: COMPARISON2 Product

Nicotrol

Nicoderm CQ

Nicotine 24 hours delivery 16 hours Strength 5 mg patch 7 mg patch 10 mg patch 15 mg patch

Generics 24 hours 7 mg patch

14 mg patch 14 mg patch 21 mg patch 21 mg patch

NICOTINE PATCH: DOSING2 Product

Light Smoker

Heavy Smoker

≤10 cigarettes/day Not indicated

>10 cigarettes/day Step 1 (15 mg x 6 weeks) Step 2 (10 mg x 2 weeks) Step 3 (5 mg x 2 weeks)

≤10 cigarettes/day Step 2 (14 mg x 6 weeks) Step 3 (7 mg x 2 weeks)

>10 cigarettes/day Step 1 (21 mg x 6 weeks) Step 2 (14 mg x 2 weeks) Step 3 (7 mg x 2 weeks)

Generic ≤10 cigarettes/day (formerly Habitrol) Step 2 (14 mg x 6 weeks) Step 3 (7 mg x 2 weeks)

>10 cigarettes/day Step 1 (21 mg x 4 weeks) Step 2 (14 mg x 2 weeks) Step 3 (7 mg x 2 weeks)

Generic ≤15 cigarettes/day (formerly ProStep) 11 mg x 6 weeks

>15 cigarettes/day 22 mg x 6 weeks

Nicotrol

Nicoderm CQ

Nicotine Patch Facts  Plasma levels 50% less than cigarettes  Slow delivery system  Alleviates withdrawal (not so with gum, lozenge, spray, inhaler)

 RCT’s – 50% higher abstinence rate vs. placebo  Highest compliance rate among NRT’s

Nicotine Patch Patient Information         

Choose area on upper body or arm Choose hairless area (do not shave) Avoid inflamed or irritated areas Rotate sites daily Do not use same area for at least a week Do not cut patches Wash hands after application, avoid eyes OK to swim, bathe, shower Do not smoke while on the patch

Nicotine Patch ADR’s  Mild redness (24 hrs) after removal  Itching, burning, tingling – 50%  OK to try OTC topical steroid or H1 antagonist

 Headache  Vivid dreams (remove HS)

Nicotine Nasal Spray  Nicotrol NS® Rx  Aqueous nicotine solution  Metered dose delivers 0.5 mg nicotine/spray  Rapid mucosal absorpton

 Fastest onset of all NRT’s (11-13 min.)

 Dose = 2 sprays (1mg)  One bottle = 160 sprays

Nicotine Nasal Spray  Dosing schedule    

Initial = 1-2 sprays q nostril/hr prn Max 10 sprays/hr Titrate up prn Usual dose = 16 sprays/day x 6-8 weeks, taper down over subsequent 4-6 weeks

 Precautions – nasal disorders, asthma  High abuse potential d/t fast nicotine release

Nicotine Nasal Spray Patient Information  Remove cap (safety cap)  Prime pump before first use or if > 24 hrs since      

last use Blow nose if necessary Tilt head back, insert tip and spray into nostril Do not sniff in or inhale while spraying Wait at least 3 min before blowing nose again Do not smoke while using the spray Wait 5 min before driving or operating machinery

Nicotine Nasal Spray ADR’s  Hot, peppery sensation in nose and back of throat – 94%  Cough  Watery eyes  Runny nose  Most sx diminish in 3 weeks  81% report continued sx at lower intensity

Nicotine Inhaler  Nicotrol Inhaler® Rx  Nicotine oral inhaler system  Re-usable mouthpiece and porous cartridge (10 mg)  Delivers 4 mg nicotine vapor + menthol to decrease irritation  Buccal absorption  Active puffing x 20 min = ~ 4 mg nicotine (2 mg absorbed)  Satisfies hand-to-mouth behavior

Nicotine Inhaler  Dosing    

6 cartridges/day Increase prn to max 16 cartridges/day 12 weeks duration Taper over subsequent 6-12 weeks

 Peak  30 min  50-70% lower plasma levels than cigarettes

Nicotine Inhaler Patient Information  Take small puffs as if lighting a pipe  Actively puff for 20 minutes (not necessarily all     

at once) Avoid deep inhalation (↑lung absorption,↑SE) Discard cartridge after 24 hrs Wash mouthpiece regularly Do not smoke while using the inhaler Do not eat or drink for 15 min. before or while using inhaler. Coffee, cola, acidic juices, wine decrease absorption

Nicotine Inhaler ADR’s  Mild mouth and throat irritation  Unpleasant taste  Cough  Dyspepsia  Hiccups  Headache  Rhinitis

Bupropion SR  Zyban®, generics Rx  Oral tablet formulation  Antidepressant  NE and dopamine  Cravings – dopamine reward pathway  Withdrawal - NE

Bupropion SR  Kinetics 5-20% bioavailable CYP2B6 metabolism (tegretol↓, ritonavir↑) MAOI interaction 87% renal elimination  t1/2 = 21 hrs (parent drug)    

20-27 hrs (metabolite) Steady state 5-8 days

Bupropion Dosing  Day 1-3 – 150mg qd  Thereafter 150mg bid x 7-12 weeks  Studies > 12 weeks show lower relapse rate

 Begin treatment 1 week prior to quitting

Bupropion Contraindications  Seizure disorder  Anorexia  Bulemia nervosa  Abrupt d/c of alcohol or benzodiazepines

Bupropion ADR’s  Insomnia (30-40%)  Take second dose 8 hrs later

 Dry mouth (11%)  Tremor (3%)  Skin rash (2%)

Bupropion  Advantages  

No adverse effects of nicotine Can be used in combination with NRT

 Disadvantages   

Seizure risk Drug interactions If ineffective after 7 weeks then d/c

Other Pharmacologic Therapies  Clonidine  Nortriptyline  SSRI’s  Mecamylamine  Benzodiazepines  Rimonabant (Acomplia®)  Nicotine vaccine (NicVax®)

Combination Therapies  Long-acting + short-acting  Patch + (gum, lozenge, inhaler, spray)  Use only in patients unable to quit on monotherapy  Risk of toxicity  No long term studies

 Bupropion + patch  ↑ 5.2% in RCT over either agent alone  Not statistically significant

Varenicline    

Chantix® Rx

May 2006 Oral dosage form Alpha-4-beta-2 nicotinic acetylcholine receptor agonist - ↓ cravings  Concomitantly blocks nicotine-receptor binding ↓ satisfaction from smoking  Stimulates receptor at lower intensity than nicotine - ↓ withdrawal

Chantix® Dosing  Days 1-3 0.5 mg qd  Days 4-7 0.5 mg bid  Days 8 – end of tx 1 mg bid  Recommended tx duration = 12 weeks  subsequent 12 weeks tx = ↑ abstinence rate

 Renal dosing  CrCl < 30 ml/min = 0.5mg bid  CrCl < 10 ml/min = 0.5mg qd

Chantix® ADR’s  Nausea (30%)  Full glass water, after meals

 Insomnia (18%)  Headache (15%)  Abnormal dreams (13%)  Other GI (5-8%)

Chantix® Information    

No drug interactions to date Pregnancy category C Not recommended in combination with NRT GET QUIT - Patient support program  1-877-CHANTIX or www.chantix.com

 2 studies vs. bupropion3,4    

12 weeks +40 week follow-up Conclusion – at least “as effective as” bupropion Superior at 24 week point

LONG-TERM (>5 month) QUIT RATES for AVAILABLE CESSATION MEDICATIONS 35

Active drug Placebo

30

Percent quit

25 20

30.5

30.5

23.9

23.7

17.1

22.8

17.7

17.3

15

12.3

13.9 10.5

10.0

10 5 0 Nicotine gum

Nicotine patch

Nicotine lozenge

Nicotine nasal spray

Nicotine inhaler

Bupropion

Data adapted from Fiore et al. Treating Tobacco Use and Dependence. Clinical Practice Guideline. USDHHS, PHS, 2000 and Shiffman et al. Arch Int Med 2002;162:1267-

COMBINATION THERAPY: PATCH PLUS BUPROPION Percentage of patients quit at 12 months after cessation Nicotine patch plus bupropion

35.5%

Bupropion

30.3%

Nicotine patch

16.4%

Placebo

15.6%

0%

5%

10%

15%

20%

25%

30%

35%

40%

Jorenby et al. N Engl J Med 1999;340(9):685–691.

COMPARATIVE DAILY COSTS of PHARMACOTHERAPY $4.00

Chantix

$6.07

Inhaler

$5.77

Gum

$4.98

Lozenge

$4.50

Cigarettes (1 PPD)

$4.02

Bupropion

$3.93

Patch

$3.40

Nasal spray

0

1

2

3

4

5

6

Cost per day (in U.S. dollars)

7

Quitting Facts Sheet  Smokers of non-filtered cigarettes less    

likely to quit than filtered smokers First cigarette < 30 minutes from waking less likely to quit Purchase by the carton less likely to quit Smokers of regular cigarettes less likely to quit than smokers of “lites” Dieting while trying to quit decreases success rate

Case Study  AJ – 49 yo HM being discharged from hospital for pneumonia and COPD exacerbation  PMH – COPD, HTN, pre-diabetes  Personal – Divorced, 3 children  Meds – Levaquin 500mg qd x 10d HCTZ 50mg qd Advair 250/50 1 puff bid albuterol 2 puffs qid prn

Case Study (AJ)  What question would you ASK first?  Do you smoke or use other forms of tobacco?  This is important to me since I have a duty to be concerned for your well being

 How may you ADVISE this patient on quitting?  Personalize – COPD, HTN, diabetes risk  This is a good opportunity to quit since you have not been able to smoke while in the hospital  Empathize and don’t judge – It’s not easy to quit

Case Study (AJ)  What ASSESS-ment tools can you use?  Fagerstrom questionnaire  How much?, How long?, When?  Previous attempts to quit?, What products?  What made you go back to smoking?  Are you ready to quit?  How confident are you that you will succeed?

Case Study (AJ)  How can you ASSIST AJ in quitting?  Set a quit date  How soon would you see him?  Select a product  Identify triggers  Make him aware of the reality of withdrawal symptoms and cravings  Coping strategies

Case Study  What ARRANGE-ments would you make for AJ?     

Follow up appointments Rx from provider if necessary On-line help Smoking cessation clinic Toll-free numbers

 Make it personal!  Get contact numbers (home, cell, work)

Helpful Web Sites  U.S. Department of Health and Human Services  www.surgeongeneral.gov/tobacco/

 UCSF School of Pharmacy  http://rxforchange.ucsf.edu/

 American Lung Association  www.lungusa.org/

 Centers for Disease Control and Prevention  www.cdc.gov/tobacco/how2quit.htm

References 1. Trends in Tobacco Use, American Lung Association-Epidemiology and Statistics Unit, Jan 2006. 2. RX for Change: Clinician-Assisted Tobacco Cessation Faculty Coordinator’s Guide. June 2003.

References 3. Jorenby DE, et al. Efficacy of varenicline, an alpha4beta2 nicotine acetylcholine receptor partial agonist, vs. placebo or sustained release bupropion for smoking cessation: a randomized controlled trial JAMA 2006;296:56-63. 4. Gonzales D, et al. Varenicline, an alpha4beta2 nicotine acetylcholine receptor partial agonist, vs. sustained release bupropion and placebo for smoking cessation: a randomized control trial JAMA 2006;296:47-55.