Transcript Jim Thigpen, PharmD, BCPS ETSU Bill Gatton College of Pharmacy    Describe the pharmacotherapy used in smoking cessation Determine the appropriate therapy to recommend for.

Jim Thigpen, PharmD, BCPS
ETSU Bill Gatton College of Pharmacy



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




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
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



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-490.917 Physician Responsibilities for Tobacco
Cessation. Adopted June 2005, Chicago IL

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
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

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 (1-800-784-8669

Cold turkey
 5% success

Unassisted tapering
 5% success

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





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;365:1222-31

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®)

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

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




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

Polacrilex gum

 Nicorette®, generics

Lozenge
 Nicorette® Lozenge
Nasal Spray
 Nicotrol ® NS

Inhaler
 Nicotrol ®
 Nicorette ® Mini Lozenge
 Generics

Transdermal Patch
 Nicoderm CQ ®
 Generics
Patients should stop using all forms of tobacco upon initiation of NRT

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

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
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 10 - 12
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

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


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

Advantages

Disadvantages
 Satisfy oral cravings
 Need for frequent
 Might delay weight
dosing
 Dental work
 Must use proper
technique
 Gum might not be
socially acceptable
gain (4 mg)
 Therapy can be titrated
to manage withdrawal
symptoms
 Flavors

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



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%
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)
Step 3 (7 mg X 2 weeks)
Generic
≤ 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 4 weeks)
Step 2 (14 mg X 2 weeks)
Step 3 (7 mg X 2 weeks)




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

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


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

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

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



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

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

Non-nicotine
Sustained release antidepressant
Oral only

Estimated abstinence rate is 24.2%



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

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

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

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

Neurophychiatric symptoms and suicidality
 Changes in mood
 Psychosis/hallucinations/paranoia/delusions
 Homicial ideation/hostility
 Agitation/anxiety/panic
 Suicidal ideation or attempts
 Completed suicide

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

Adverse Effects (> 5% and x2 higher than placebo)
 Nausea
 Sleep disturbances
 Constipation
 Flatulance
 Vomiting
 Vivid dreams (< 5%)

Clonidine
 α2-adrenergic agonist that reduces sympathetic
outflow that reduces the autonomic symptoms of
withdrawal
 May be beneficial

Nortriptyline
 TCA
 May be beneficial
Nasal Spray
25
Bupropion
23.9
20
Patch
15 18
15.8
16.1
17.1
19
20.2
10
5
0
Gum
Lozenge
Inhaler
Verenicline

Combination NRT
 Patch + gum/inhaler/nasal spray

Bupropion + Nicotine patch
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