Assisting a Quitter – The Medications Used in Smoking Cessation

Jim Thigpen, PharmD, BCPSETSU Bill Gatton College of Pharmacy

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

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

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

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-490.917 Physician Responsibilities for Tobacco Cessation. Adopted June 2005, Chicago IL

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

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

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 (1-800-784-8669

Nonpharmacologic

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

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;365:1222-31

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®)

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

PharmacotherapyNot 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

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

NRT Products

Polacrilex gum Nicorette®, generics

Lozenge Nicorette® Lozenge Nicorette ® Mini

Lozenge Generics

Transdermal Patch

Nicoderm CQ ®

Generics

Nasal Spray Nicotrol ® NS

Inhaler Nicotrol ®

Patients should stop using all forms of tobacco upon initiation of NRT

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

Nicotine GumNicorette® (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

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 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

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

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

Nicotine Gum

Advantages 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

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

Transdermal nicotine patchNicoderm® 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%

Transdermal nicotine patch

Product Light Smoker Heavy Smoker

Nicoderm® CQ ≤ 10 cigarettes/dayStep 2 (14 mg X 6 weeks)Step 3 (7 mg X 2 weeks)

10 cigarettes/dayStep 1 (21 mg X 6 weeks)Step 2 (14 mg X 2 weeks)Step 3 (7 mg X 2 weeks)

Generic ≤ 10 cigarettes/dayStep 2 (14 mg X 6 weeks)Step 3 (7 mg X 2 weeks)

10 cigarettes/dayStep 1 (21 mg X 4 weeks)Step 2 (14 mg X 2 weeks)Step 3 (7 mg X 2 weeks)

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

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

Nicotine nasal sprayNicotrol® 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

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

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

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

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

Bupropion SRZyban®, generics

Non-nicotine Sustained release antidepressant Oral only

Estimated abstinence rate is 24.2%

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

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

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

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

Varenicline

Neurophychiatric symptoms and suicidality Changes in mood Psychosis/hallucinations/paranoia/

delusions Homicial ideation/hostility Agitation/anxiety/panic Suicidal ideation or attempts Completed suicide

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

Verenicline

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

Second-line therapies

Clonidine α2-adrenergic agonist that reduces

sympathetic outflow that reduces the autonomic symptoms of withdrawal

May be beneficial Nortriptyline

TCA May be beneficial

Long-term (> 6 month) quit rates

1815.8 16.1

23.9

17.119 20.2

0

5

10

15

20

25

Gum Lozenge Inhaler Verenicline

Patch

Nasal Spray

Bupropion

Combination Pharmacotherapy

Combination NRT Patch + gum/inhaler/nasal spray

Bupropion + Nicotine patch

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