TOBACCO DEPENDENCE: a 2‐PART PROBLEM Tobacco Dependence

TOBACCO DEPENDENCE: A 2‐PART PROBLEM Tobacco Dependence

Physiological Behavioral

MEDICATIONS for CESSATION The addiction to nicotine The habit of using tobacco

Treatment Treatment

Medications for cessation Behavior change program

Treatment should address the physiological and the behavioral aspects of dependence.

NICOTINE WITHDRAWAL SYMPTOMS: Time Course* and Management PHARMACOTHERAPY Irritability / Frustration / Anger “ Anxiety Most symptoms manifest within Clinicians should encourage all patients Difficulty concentrating the first 1–2 days, peak within Restlessness / Impatience attempting to quit to use effective Depressed mood / Depression the first week, and subside Insomnia within 2–4 weeks. medications for tobacco dependence Impaired task performance Increased appetite 6 months treatment, except where contraindicated Weight gain Can persist for months Cravings or for specific populations* for which there to years after quitting 1 week 4 weeks 12 weeks is insufficient evidence of effectiveness.” Quit Former Recent quitter * Includes pregnant women, smokeless tobacco users, light smokers, and adolescents. date tobacco user  Cognitive & behavioral coping strategies Medications significantly improve success rates.  Medications for cessation Fiore et al. (2008). Treating Tobacco Use and Dependence: 2008 Update. *Timeline aspect of the figure is not according to scale. Data from Hughes. (2007). Nicotine Tob Res 9:315–327. Clinical Practice Guideline. Rockville, MD: USDHHS, PHS, May 2008.

PHARMACOTHERAPY: FDA‐APPROVED MEDICATIONS Use in SPECIAL POPULATIONS for CESSATION Pharmacotherapy is not recommended for: Nicotine polacrilex gum* Nicotine inhaler *  Pregnant smokers . Nicorette (OTC) . Nicotrol (Rx)  Insufficient evidence of effectiveness . Generic nicotine gum (OTC) Nicotine nasal spray *  Smokeless tobacco users Nicotine lozenge*  No FDA indication for smokeless tobacco cessation . Nicotrol NS (Rx) . Nicorette (OTC)  Individuals smoking fewer than 10 cigarettes per day . Generic nicotine lozenge (OTC) Bupropion SR  Adolescents . Generic (Rx)  Nonprescription sales of nicotine replacement therapy (NRT) products Nicotine transdermal patch* (i.e., patch, gum, lozenge) are restricted to adults ≥18 years of age . Habitrol (OTC) Varenicline  NRT use in minors requires a prescription . NicoDerm CQ (OTC) . Chantix (Rx) . Generic nicotine patches (OTC) Recommended treatment is behavioral counseling. * Nicotine replacement therapy (NRT) products.

1 NICOTINE REPLACEMENT THERAPY PLASMA NICOTINE CONCENTRATIONS (NRT) RATIONALE for USE for NICOTINE‐CONTAINING PRODUCTS

. Reduces physical withdrawal from nicotine Cigarette 25 Moist snuff Cigarette . Eliminates the immediate, reinforcing effects of 20 Moist snuff Nasal spray

nicotine that is rapidly absorbed via tobacco (mcg/l) 15 smoke Inhaler nicotine

10 . Allows patient to focus on behavioral and Lozenge (2mg)

Plasma 5 psychological aspects of tobacco cessation Gum (2mg) 0 1/0/1900 1/10/1900 1/20/1900 1/30/1900 2/9/1900 2/19/1900 2/29/1900 Patch 0 10 20 30 40 50 60 NRT products approximately doubles quit rates. Time (minutes)

NICOTINE GUM NRT: PRECAUTIONS Nicorette; generics

 Resin complex  Patients with underlying cardiovascular disease  Nicotine  Recent myocardial infarction (within past 2  Polacrilin

weeks)  Sugar‐free chewing gum base

 Serious arrhythmias  Contains buffering agents to enhance buccal absorption of nicotine  Serious or worsening angina  Available: 2 mg, 4 mg; original, cinnamon, fruit, and mint (various) flavors NRT products may be appropriate for these patients if they are under medical supervision.

NICOTINE LOZENGE NICOTINE GUM & LOZENGE: Nicorette Lozenge, Nicorette Mini Lozenge; generics DOSING . Nicotine polacrilex formulation Dose based on the “time to first cigarette” (TTFC) . Delivers ~25% more nicotine as an indicator of nicotine dependence than equivalent gum dose Use the 2 mg gum/lozenge: . Sugar‐free mint, cherry flavors If first cigarette of the day is smoked . Contains buffering agents to more than 30 minutes after waking enhance buccal absorption of Use the 4 mg gum/lozenge: nicotine If first cigarette of the day is . Available: 2 mg, 4 mg smoked within 30 minutes of waking

2 NICOTINE GUM & LOZENGE: NICOTINE GUM: DOSING (cont’d) DIRECTIONS FOR USE

Chew slowly Recommended Usage Schedule Stop chewing at first Weeks 1–6 Weeks 7–9 Weeks 10–12 Chew again when peppery taste or sign of peppery taste 1 piece q 1–2 h1 piece q 2–4 h1 piece q 4–8 h tingle fades or tingling sensation

Park between Do not use more than 24 pieces of GUM cheek & gum or 20 LOZENGES per day.

NICOTINE LOZENGE: NICOTINE GUM/LOZENGE: DIRECTIONS for USE ADDITIONAL PATIENT EDUCATION . Place in mouth and allow to dissolve slowly . To improve chances of quitting, use at least nine pieces (nicotine release may cause warm, tingling daily during the first 6 weeks sensation) . The gum/lozenge will not provide the same rapid satisfaction that smoking provides . Do not chew or swallow . The effectiveness of the nicotine gum/lozenge may be . Occasionally rotate to different areas of the mouth reduced by some foods and beverages: . Lozenges will dissolve completely in about 2030 − Coffee − Juices minutes − Wine − Soft drinks Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine gum or lozenge.

NICOTINE GUM/LOZENGE: NICOTINE GUM/LOZENGE: ADD’L PATIENT EDUCATION (cont’d) ADD’L PATIENT EDUCATION (cont’d) . Chewing the lozenge or using incorrect gum chewing . Adverse effects of nicotine gum and lozenge: technique can cause excessive and rapid release of . Mouth and throat irritation nicotine, resulting in: . Hiccups . Lightheadedness/dizziness . Gastrointestinal complaints (dyspepsia, nausea) . Nausea and vomiting . Adverse effects associated with nicotine gum: . Hiccups . Jaw muscle ache . Irritation of throat and mouth . May stick to dental work

3 NICOTINE GUM/LOZENGE: TRANSDERMAL NICOTINE PATCH SUMMARY Habitrol; NicoDerm CQ; generic ADVANTAGES DISADVANTAGES . Continuous (24‐hour) nicotine delivery system  Might serve as an oral substitute  Need for frequent dosing can compromise for tobacco adherence . Nicotine is well absorbed across the skin

 Might delay weight gain  Gastrointestinal adverse effects (nausea, . Transdermal delivery to systemic circulation avoids hepatic  Can be titrated to manage hiccups, and dyspepsia) may be bothersome first‐pass metabolism withdrawal symptoms  Specific to nicotine gum: . Plasma nicotine levels are lower and fluctuate less than  Can be used in combination with . Might be problematic for patients with significant other agents to manage situational dental work with smoking urges . Proper chewing technique is necessary for effectiveness and to minimize adverse effects  Relatively inexpensive . Chewing might not be acceptable or desirable for some patients

TRANSDERMAL NICOTINE PATCH: TRANSDERMAL NICOTINE PATCH: DOSING DIRECTIONS for USE . Choose an area of skin on the Product Light Smoker Heavy Smoker upper body or upper outer part of 10 cigarettes/day >10 cigarettes/day the arm Step 2 (14 mg x 6 weeks) Step 1 (21 mg x 6 weeks) NicoDerm CQ . Make sure skin is clean, dry, Step 3 (7 mg x 2 weeks) Step 2 (14 mg x 2 weeks) hairless, and not irritated Step 3 (7 mg x 2 weeks) . Apply patch to different area each 10 cigarettes/day >10 cigarettes/day day Habitrol Step 2 (14 mg x 6 weeks) Step 1 (21 mg x 4 weeks) . Do not use same area again for at Generic Step 3 (7 mg x 2 weeks) Step 2 (14 mg x 2 weeks) least 1 week Step 3 (7 mg x 2 weeks)

TRANSDERMAL NICOTINE PATCH: TRANSDERMAL NICOTINE PATCH: DIRECTIONS for USE (cont’d) DIRECTIONS for USE (cont’d) . Remove protective liner and . Wash hands: Nicotine on hands can get into eyes apply adhesive side of patch to skin or nose and cause stinging or redness . Peel off remaining protective . Do not leave patch on skin for more than 24 covering hours—doing so may lead to skin irritation . Press firmly with palm of . Adhesive remaining on skin may be removed with hand for 10 seconds rubbing alcohol or acetone . Make sure patch sticks well to skin, especially around . Dispose of used patch by folding it onto itself, edges completely covering adhesive area

4 TRANSDERMAL NICOTINE PATCH: TRANSDERMAL NICOTINE PATCH: ADDITIONAL PATIENT EDUCATION ADD’L PATIENT EDUCATION (cont’d)

 Water will not harm the nicotine patch if it is applied correctly; Common adverse effects include: patients may bathe, swim, shower, or exercise while wearing the patch . Irritation at the patch application site (generally  Do not cut patches to adjust dose within the first hour) . Mild itching  Can unpredictably effect nicotine delivery . Burning  Patch may be less effective . Tingling  Keep new and used patches out of the reach of . Sleep disturbances children and pets . Abnormal or vivid dreams . Insomnia  Remove patch before MRI procedures

TRANSDERMAL NICOTINE PATCH: TRANSDERMAL NICOTINE PATCH: ADD’L PATIENT EDUCATION (cont’d) SUMMARY . After patch removal, skin may appear red for 24 hours ADVANTAGES . If skin stays red more than 4 days or if it swells or a rash DISADVANTAGES appears, contact health care provider—do not apply new patch  Once‐daily dosing associated with . When used as monotherapy, fewer adherence problems cannot be titrated to acutely . Local skin reactions (redness, burning, itching) manage withdrawal symptoms . Usually caused by adhesive  Of all NRT products, its use is least obvious to others . Not recommended for use by . Up to 50% of patients experience this reaction patients with dermatologic . Fewer than 5% of patients discontinue therapy  Can be used in combination with conditions (e.g., psoriasis, . Avoid use in patients with dermatologic conditions (e.g., other agents; delivers consistent eczema, atopic dermatitis) psoriasis, eczema, atopic dermatitis) nicotine levels over 24 hrs  Relatively inexpensive

NICOTINE INHALER NICOTINE INHALER: Nicotrol Inhaler SCHEMATIC DIAGRAM

. Nicotine inhalation system Air/nicotine mixture out consists of: Sharp point that breaks the seal Aluminum laminate . Mouthpiece sealing material . Cartridge with porous plug containing 10 mg nicotine and 1 Sharp point that Mouthpiece mg menthol breaks the seal

. Delivers 4 mg nicotine vapor, Porous plug impregnated with nicotine absorbed across buccal Nicotine Air in cartridge mucosa Reprinted with permission from Schneider et al. (2001). Clinical Pharmacokinetics 40:661–684. Adis International, Inc.

5 NICOTINE INHALER: NICOTINE INHALER: DOSING DIRECTIONS for USE

 Initial treatment (up to 12 weeks)

 Start with at least 6 cartridges/day during the first 3–6 weeks of .Align marks on mouthpiece treatment

 Increase prn to maximum of 16 cartridges/day

 In general, use 1 cartridge every 1–2 hours

 Gradually reduce daily dosage over the following 6–12 weeks .Pull and separate mouthpiece into two parts  Recommended maximum duration of therapy is 6 months

NICOTINE INHALER: NICOTINE INHALER: DIRECTIONS for USE (cont’d) DIRECTIONS for USE (cont’d) . Press nicotine cartridge . During inhalation, nicotine is vaporized and absorbed across firmly into bottom of oropharyngeal mucosa mouthpiece until it pops . Inhale into back of throat or puff in short breaths into place . Nicotine in cartridges is depleted after about 20 minutes of active puffing . Cartridge does not have to be used all at once—try different schedules  Line up the markings on the mouthpiece again and (e.g., 5 minutes at a time) to find what works best push the two pieces back together so they fit tightly . Open cartridge retains potency for 24 hours  Twist the top to misalign marks and secure unit . Mouthpiece is reusable; clean regularly with mild detergent

NICOTINE INHALER: NICOTINE INHALER: ADDITIONAL PATIENT EDUCATION ADD’L PATIENT EDUCATION (cont’d)

. Adverse effects associated with the nicotine inhaler include:  Use inhaler at room temperature (>60F); in cold environments, the delivery of nicotine vapor may be . Mild irritation of the mouth or throat compromised

. Cough  Use the inhaler longer and more often at first to help control . Hiccups cravings (best results are achieved with frequent continuous puffing over 20 minutes)

. Gastrointestinal complaints (dyspepsia, nausea)  Effectiveness of the nicotine inhaler may be reduced by some . Severity generally rated as mild, and frequency of foods and beverages symptoms declined with continued use Do NOT eat or drink for 15 minutes BEFORE or while using the nicotine inhaler.

6 NICOTINE NASAL SPRAY NICOTINE INHALER: SUMMARY Nicotrol NS ADVANTAGES DISADVANTAGES . Aqueous solution of nicotine in a 10‐ml spray bottle  Might serve as an oral substitute . Need for frequent dosing can for tobacco compromise adherence . Each metered dose actuation

 Can be titrated to manage . Cartridges might be less effective delivers withdrawal symptoms in cold environments (≤60F) . 50 mcL spray . Cost of treatment  Mimics the hand‐to‐mouth . 0.5 mg nicotine ritual of smoking . ~100 doses/bottle  Can be used in combination with other agents to manage . Rapid absorption across nasal situational urges mucosa

NICOTINE NASAL SPRAY: NICOTINE NASAL SPRAY: DOSING & ADMINISTRATION DIRECTIONS for USE . One dose = 1 mg nicotine . Press in (2 sprays, one 0.5 mg spray in each nostril) circles on . Start with 1–2 doses per hour sides of . Increase as needed to maximum dosage of 5 doses per hour or 40 mg (80 sprays; ~½ bottle) daily bottle and pull to . At least 8 doses daily for the first 6–8 weeks remove cap . Termination: . Gradual tapering over an additional 4–6 weeks . Recommended maximum duration of therapy is 3 months

NICOTINE NASAL SPRAY: NICOTINE NASAL SPRAY: DIRECTIONS for USE (cont’d) DIRECTIONS for USE (cont’d) . Prime the pump (before first use) . If nose runs, gently sniff to keep nasal spray in nose . Re‐prime (1–2 sprays) if spray not used for 24 hours . Blow nose (if not clear) . Wait 2–3 minutes before blowing nose . Tilt head back slightly and insert tip of bottle . Avoid contact with skin, eyes, and mouth into nostril as far as comfortable . If contact occurs, rinse with water immediately . Breathe through mouth, and spray once in each nostril . Nicotine is absorbed through skin and mucous membranes . Do not sniff or inhale while spraying

7 NICOTINE NASAL SPRAY: NICOTINE NASAL SPRAY: ADDITIONAL PATIENT EDUCATION SUMMARY . What to expect (first week): ADVANTAGES DISADVANTAGES . Hot peppery feeling in back of throat or nose . Sneezing  Can be titrated to rapidly . Need for frequent dosing can . Coughing manage withdrawal compromise adherence . Watery eyes symptoms . Nasal administration might not . Runny nose be acceptable/desirable for some  Can be used in combination patients; nasal irritation often . Adverse effects should lessen over a few days with other agents to manage problematic . Regular use during the first week will help in development of tolerance to the . Not recommended for use by irritant effects of the spray situational urges patients with chronic nasal . If adverse effects persist after a week, contact health care provider and consider disorders or severe reactive alternative treatment airway disease . Cost of treatment

BUPROPION SR BUPROPION: Generics PHARMACOKINETICS . Non‐nicotine cessation aid Absorption . Mechanism of action: atypical antidepressant thought . Bioavailability: 5–20% to affect levels of various brain neurotransmitters Metabolism . Dopamine . Undergoes extensive hepatic metabolism (CYP2B6) . Norepinephrine Elimination . Clinical effects . Urine (87%) and feces (10%) .  craving for cigarettes Half‐life .  symptoms of nicotine withdrawal . Bupropion (21 hours); metabolites (20–37 hours)

BUPROPION: BUPROPION: CONTRAINDICATIONS WARNINGS and PRECAUTIONS

. Seizure disorder Use with caution in the following populations:  Patients with an elevated risk for seizures, including: . Current or prior diagnosis of bulimia or anorexia  Severe head injury nervosa  Concomitant use of medications that lower the seizure threshold . Abrupt discontinuation of alcohol, benzodiazepines, (e.g., other bupropion products, antipsychotics, tricyclic barbiturates and antiepileptic drugs antidepressants, theophylline) . Use of MAO inhibitors (within 14 days of initiating or  Severe hepatic impairment discontinuing therapy)  Patients with underlying neuropsychiatric conditions For a comprehensive listing of warnings and precautions, refer to the manufacturer’s prescribing information.

8 BUPROPION: WARNINGS and PRECAUTIONS (cont’d) BUPROPION SR: DOSING

. Neuropsychiatric symptoms and suicide risk To ensure therapeutic plasma levels of the drug are achieved, . Changes in mood (including depression and mania) begin therapy 1 to 2 weeks PRIOR to the quit date. FDA boxed . Psychosis/hallucinations/paranoia/delusions warning Initial treatment . Homicidal ideation removed  150 mg po q AM for 3 days . Aggression/hostility/anxiety/panic Dec 2016 Then… . Suicidal ideation, suicide attempt, completed suicide  150 mg po bid for 7–12 weeks

 Doses must be administered at least 8 hours apart Advise patients to stop taking bupropion SR and contact a health care provider immediately if symptoms such as agitation, depressed mood, or changes in behavior or thinking that are not  Tapering not necessary when discontinuing therapy typical are observed or if the patient develops suicidal ideation or suicidal behavior.

BUPROPION: ADVERSE EFFECTS BUPROPION SR: SUMMARY Common adverse effects include the following: ADVANTAGES DISADVANTAGES

 Insomnia (avoid bedtime dosing)  Oral dosing is simple and . Seizure risk is increased associated with fewer adherence  Dry mouth . problems Several contraindications and  Nausea precautions preclude use in some  Might delay weight gain patients

Less common but reported effects:  Bupropion might be beneficial in . Patients should be monitored for  Anxiety/difficulty concentrating patients with depression neuropsychiatric symptoms  Constipation  Can be used in combination with NRT agents  Tremor  Relatively inexpensive  Skin rash

VARENICLINE VARENICLINE: Chantix MECHANISM of ACTION

    Nonnicotine Binds with high affinity and selectivity at 4 2 neuronal nicotinic acetylcholine receptors cessation aid  Stimulates low‐level agonist activity

 Competitively inhibits binding of nicotine  Partial nicotinic receptor agonist  Clinical effects   symptoms of nicotine withdrawal

  Blocks dopaminergic stimulation responsible for reinforcement & Oral formulation reward associated with smoking

9 VARENICLINE: VARENICLINE: PHARMACOKINETICS WARNINGS and PRECAUTIONS

Absorption  Neuropsychiatric symptoms and suicide risk

 Virtually complete (~90%) after oral administration; not affected by food  Changes in mood (including depression and mania) FDA boxed Metabolism  Psychosis/hallucinations/paranoia/delusions warning  Undergoes minimal metabolism  Homicidal ideation removed Elimination Dec 2016  Aggression/hostility/anxiety/panic  Primarily renal through glomerular filtration and active tubular secretion; 92% excreted unchanged in urine  Suicidal ideation, suicide attempt, completed suicide

Half‐life Advise patients to stop taking varenicline and contact a health care provider immediately if  24 hours symptoms such as agitation, depressed mood, or changes in behavior or thinking that are not typical are observed or if the patient develops suicidal ideation or suicidal behavior.

VARENICLINE: VARENICLINE: WARNINGS and PRECAUTIONS (cont’d) STANDARD DOSING In some patients, use of varenicline has been associated with: Patients should begin therapy 1 week PRIOR to their quit date. The dose is gradually increased to minimize treatment‐related nausea and insomnia.  Seizures

 Enhanced effects of alcohol Treatment Day Dose  Accidental injury Day 1 to day 30.5 mg qd  Cardiovascular events Initial dose  Somnambulism Day 4 to day 70.5 mg bid titration  Angioedema and hypersensitivity reactions Day 8 to end of treatment* 1 mg bid  Serious skin reactions * Up to 12 weeks These are rare events and most have not been causally linked to varenicline use.

VARENICLINE: VARENICLINE QUIT APPROACHES ADVERSE EFFECTS FIXED QUIT approach Common adverse effects include the following: . Set quit date for 1 week after starting varenicline . Continue treatment for 12 weeks . Nausea FLEXIBLE QUIT approach . Insomnia . Start taking varenicline and pick a quit date between 8 . Abnormal dreams to 35 days from treatment initiation . Continue treatment for 12 weeks . Headache GRADUAL QUIT approach Less common adverse effects: . Start taking varenicline and reduce smoking by 50% within the first 4 weeks, an additional 50% in the next 4 . Gastrointestinal (flatulence, constipation) weeks, and continue until complete abstinence by 12 weeks . Taste alteration Images from: https://www.pfizerpro.com/product/chantix/hcp/quit‐approaches.

10 VARENICLINE: ADDITIONAL PATIENT EDUCATION VARENICLINE: SUMMARY . Doses should be taken after eating, with a full glass of water ADVANTAGES DISADVANTAGES

. Nausea and insomnia are usually temporary side effects  Oral dosing is simple and . Cost of treatment . If symptoms persist, notify your health care provider associated with fewer adherence . Patients should be monitored for problems potential neuropsychiatric symptoms . May experience vivid, unusual or strange dreams during  Offers a different mechanism of treatment action for persons who have failed . Use caution driving, drinking alcohol, and operating other agents machinery until effects of quitting smoking with varenicline  Most effective agent for cessation are known when used as monotherapy

LONG‐TERM (6 month) QUIT RATES for AVAILABLE CESSATION MEDICATIONS COMBINATION PHARMACOTHERAPY 30 28.5 Combination NRT [first‐line, recommended treatment approach] Active drug Placebo 25 23.9 . Long‐acting formulation (patch) 21.0 ─ Produces relatively constant levels of nicotine 20 19.0 17.1 16.3 15.7 PLUS quit 15 12.9 12.4 . Short‐acting formulation (gum, inhaler, lozenge, nasal spray) 11.8 11.0 10.0 10 9.4 9.1 ─ Allows for acute dose titration as needed for nicotine withdrawal symptoms Percent

5 Other combinations [evidence less compelling] . Bupropion + NRT 0 Nicotine Nicotine Nicotine Nicotine Nicotine Bupropion SR Varenicline . Varenicline + NRT gum patch lozenge nasal spray inhaler . Varenicline + bupropion SR Data adapted from Cahill et al. (2016); Hartmann‐Boyce et al. (2018); Howes et al. (2020). Cochrane Database Syst Rev.

COMBINATION NRT: TREATMENT OPTIONS TREATMENT REGIMENS Multiple Treatment Comparison Meta‐Analysis . Nicotine patch Comparison Odds ratio (95% CI) Dose: 21 mg/day x 4–6 weeks  14 mg/day x 2 weeks  7 mg/day x 2 weeks Nicotine gum vs Placebo 1.7 (1.5–1.9) PLUS Bupropion SR vs Placebo 1.9 (1.6–2.1) . Nicotine gum or lozenge (2 mg/4 mg; based on TTFC) Nicotine patch vs Placebo 1.9 (1.7–2.1) Dose: Use 1 piece q 1–2 hours as needed Other NRT* vs Placebo 2.0 (1.8–2.4) OR Combination NRT vs Placebo 2.7 (2.1–3.7) . Nicotine inhaler (10 mg cartridge; delivers 4 mg nicotine vapor) Varenicline vs Placebo 2.9 (2.4–3.5) Dose: Use 1 cartridge q 1–2 hours as needed *Includes nicotine nasal spray, lozenge, and inhaler OR Strong evidence that combination NRT and varenicline are more effective . Nicotine nasal spray (0.5 mg/spray) than bupropion SR or NRT monotherapy Dose: Use 1 spray in each nostril q 1–2 hours as needed Cahill et al. (2013). Cochrane Database Syst Rev 5:CD009329.

11 ESSENTIAL QUESTION for SELECTION of NRT PRODUCT(s)* “Drugs don’t work… “Would it be a challenge for you to take a medication frequently throughout the day (e.g., a minimum of 8 or 9 times)?” . With the exception of the nicotine patch, all NRT formulations …in patients who don’t require frequent dosing throughout the day. take them.” . If patient is unable to adhere to the recommended dosing, these products should be ruled out as monotherapy because they will C. Everett Koop, M.D., former U.S. Surgeon General be ineffective.

Medication adherence should be * Product‐specific screening—e.g., for warnings, precautions, and personal preferences—is also essential. addressed at each encounter.

COMPARATIVE DAILY COSTS ADHERENCE IS KEY to QUITTING of PHARMACOTHERAPY

. Promote adherence with prescribed regimens $18 Average $/pack of cigarettes in the US, $7.19 . Select the correct strength of medication $16 $14 . Use daily (according to a fixed schedule, NOT as needed) $12 . Complete the recommended duration of therapy $10 . Consider telling the patient: $/day $8 . “If used correctly, the medicines will make you more comfortable while quitting.” $6 $4 . “Medicines work best when taken regularly, to prevent withdrawal symptoms $2 before they occur. If you wait until you’re already craving a cigarette, it will be $0 too late. The medicines don’t work as fast as inhaled nicotine from a cigarette.” Gum Lozenge Patch Nasal spray Inhaler Bupropion SR Varenicline Trade $5.49 $4.23 $3.49 $9.64 $16.38 $17.20 Generic $1.90 $2.97 $1.52 $0.72 At each encounter, assess withdrawal and adjust treatment as needed. *Wholesale acquisition cost from Red Book Online. Thomson Reuters, January 2021.

SUMMARY

 To maximize success, interventions should include behavioral counseling and one or more medications

 Encourage the use of effective medications by all patients attempting to quit smoking

 Exceptions include medical contraindications or specific populations for which there is insufficient evidence of effectiveness

 First‐line medications that reliably increase long‐term smoking cessation rates:  Bupropion SR  Nicotine replacement therapy (as monotherapy or combination therapy)  Varenicline

 Varenicline and combination NRT demonstrate the highest efficacy