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

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

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

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

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

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

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

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

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

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

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

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

13. Pharmacotherapy Not recommended for…..
Smokeless tobacco users
No FDA indication
Individuals smoking < 10 cigarettes per day
Adolescents
OTC sales are restricted to ≥ 18
NRT use in minors requires a prescription

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

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

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

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

18. Nicotine Gum Dosage based on current smoking patterns:
If patient smokes
Recommended strength
≥ 25 cigarettes (1 pack)/day
4 mg
< 25 cigarettes/day
2 mg
Recommended Usage Schedule for Nicotine Gum
Weeks 1 - 6
Weeks 7-9
Weeks
1 piece q 1 – 2 h
1 piece q 2 – 4 h
1 piece q 4 – 8 h
Do not use more than 24 pieces per day
Fiore MC, Jaen CR, Baker TB, et al. (2008) Treating tobacco use and dependence, 2008 Update. Clinical Practice Guideline. Rockville, MD: US DHHS

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

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

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

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

23. Transdermal nicotine patch Nicoderm® CQ, generics
Nicotine is well absorbed across the skin
Delivery to systemic circulation avoids hepatic first pass effect
Plasma nicotine levels are lower and fluctuate less than with smoking
Treatment
Estimated abstinence rate
Placebo
13.8%
Nicotine patch (6-14 weeks)
23.4%
Nicotine patch (> 14 weeks)
23.7%

24. Transdermal nicotine patch
Product
Light Smoker
Heavy Smoker
Nicoderm® CQ
≤ 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)
Generic
Step 1 (21 mg X 4 weeks)

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

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

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

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

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

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

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

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

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

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

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

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

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

38. Varenicline
Patients should begin therapy 1 week prior to their quit date
Treatment Day
Dose
Day 1 to day 3
0.5 mg daily
Day 4 to day 7
0.5 mg BID
Day 8 to end of treatment
1 mg BID

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

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

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

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

43. Comparative Daily Costs
Gum
Lozenge
Patch
Inhaler
Nasal Spray
Bupropion
Verencline
$4.68
$4.95
$3.89
$7.02
$3.92
$7.78
$4.70
$2.16
$3.24
$1.90
$3.62