Table 1.

Pharmacologic product guide: FDA-approved medications for smoking cessation

Nicotine Replacement Therapy (NRT) Formulations						Bupropion SR	Varenicline
	Gum	Lozenge	Transdermal Patch	Nasal Spray	Oral Inhaler	Bupropion SR	Varenicline
Product	Nicorette,^a Generic OTC 2 mg, 4 mg original, cinnamon, fruit, mint	Nicorette Lozenge,^a Nicorette Mini Lozenge^a Generic OTC 2 mg, 4 mg; cherry, mint	NicoDerm CQ,^a Generic OTC (NicoDerm CQ, generic) Rx (generic) 7 mg, 14 mg, 21 mg (24-hour release)	Nicotrol NS^b Rx Metered spray 10 mg/mL aqueous nicotine solution	Nicotrol Inhaler^b Rx 10 mg cartridge delivers 4 mg inhaled nicotine vapor	Zyban,^a Generic Rx 150 mg sustained-release tablet	Chantix^b Rx 0.5 mg, 1 mg tablet
Precautions	Recent (≤2 weeks) myocardial infarction Serious underlying arrhythmias Serious or worsening angina pectoris Temporomandibular joint disease Pregnancy^c and breastfeeding Age <18 years	Recent (≤2 weeks) myocardial infarction Serious underlying arrhythmias Serious or worsening angina pectoris Pregnancy^c and breastfeeding Age <18 years	Recent (≤2 weeks) myocardial infarction Serious underlying arrhythmias Serious or worsening angina pectoris Pregnancy^c (Rx formulations, category D) and breastfeeding Age <18 years	Recent (≤2 weeks) myocardial infarction Serious underlying arrhythmias Serious or worsening angina pectoris Underlying chronic nasal disorders (rhinitis, nasal polyps, sinusitis) Severe reactive airway disease Pregnancy^c (category D) and breastfeeding Age <18 years	Recent (≤2 weeks) myocardial infarction Serious underlying arrhythmias Serious or worsening angina pectoris Bronchospastic disease Pregnancy^c (category D) and breastfeeding Age < 18 years	Concomitant therapy with medications/conditions known to lower the seizure threshold Hepatic impairment Pregnancy^c (category C) and breastfeeding Age <18 years Warning: Black-boxed warning for neuropsychiatric symptoms^d Contraindications: Seizure disorder Concomitant bupropion (e.g., Wellbutrin) therapy Current or prior diagnosis of bulimia or anorexia nervosa Simultaneous abrupt discontinuation of alcohol or sedatives/benzodiazepines MAO inhibitors in preceding 14 days; concurrent use of reversible MAO inhibitors (e.g., linezolid, methylene blue)	Severe renal impairment (dosage adjustment is necessary) Pregnancy^c (category C) and breastfeeding Age <18 years Warning: Black-boxed warning for neuropsychiatric symptoms^d
Dosing	1^st cigarette ≤30 minutes after waking: 4 mg 1st cigarette >30 minutes after waking: 2 mg Weeks 1–6: 1 piece q 1–2 hours Weeks 7–9: 1 piece q 2–4 hours Weeks 10–12: 1 piece q 4–8 hours Maximum, 24 pieces/ day Chew each piece slowly Park between cheek and gum when peppery or tingling sensation appears (~15–30 chews) Resume chewing when tingle fades Repeat chew/park steps until most of the nicotine is gone (tingle does not return; generally 30 min) Park in different areas of mouth No food or beverages 15 minutes before or during use Duration: up to 12 weeks	1^st cigarette ≤30 minutes after waking: 4 mg 1st cigarette >30 minutes after waking: 2 mg Weeks 1–6: 1 lozenge q 1–2 hours Weeks 7–9: 1 lozenge q 2–4 hours Weeks 10–12: 1 lozenge q 4–8 hours Maximum, 20 lozenges/day Allow to dissolve slowly (20–30 minutes for standard; 10 minutes for mini) Nicotine release may cause a warm, tingling sensation Do not chew or swallow Occasionally rotate to different areas of the mouth No food or beverages 15 minutes before or during use Duration: up to 12 weeks	>10 cigarettes/day: 21 mg/day × 4–6 weeks 14 mg/day × 2 weeks 7 mg/day × 2 weeks ≤10 cigarettes/day: 14 mg/day × 6 weeks 7 mg/day × 2 weeks May wear patch for 16 hours if patient experiences sleep disturbances (remove at bedtime) Duration: 8–10 weeks	1–2 doses/hour (8–40 doses/day) One dose ≤ 2 sprays (one in each nostril); each spray delivers 0.5 mg of nicotine to the nasal mucosa Maximum 5 doses/hour or 40 doses/day For best results, initially use at least 8 doses/day Do not sniff, swallow, or inhale through the nose as the spray is being administered Duration: 3–6 months	6–16 cartridges/day Individualize dosing; initially use 1 cartridge q 1–2 hours Best effects with continuous puffing for 20 minutes Initially use at least 6 cartridges/day Nicotine in cartridge is depleted after 20 minutes of active puffing Inhale into back of throat or puff in short breaths Do NOT inhale into the lungs (like a cigarette) but “puff ” as if lighting a pipe Open cartridge retains potency for 24 hours No food or beverages 15 minutes before or during use Duration: 3–6 months	150 mg po q AM × 3 days, then 150 mg po bid Do not exceed 300 mg/day Begin therapy 1–2 weeks prior to quit date Allow at least 8 hours between doses Avoid bedtime dosing to minimize insomnia Dose tapering is not necessary Duration: 7–12 weeks, with maintenance up to 6 months in selected patients	Days 1–3: 0.5 mg po q AM Days 4–7: 0.5 mg po bid Weeks 2–12: 1 mg po bid Begin therapy 1 week prior to quit date Take dose after eating and with a full glass of water Dose tapering is not necessary Dosing adjustment is necessary for patients with severe renal impairment Duration: 12 weeks; an additional 12-week course may be used in selected patients
Adverse Effects	Mouth/jaw soreness Hiccups Dyspepsia Hypersalivation Effects associated with incorrect chewing technique: Lightheadedness Nausea/vomiting Throat and mouth irritation	Nausea Hiccups Cough Heartburn Headache Flatulence Insomnia	Local skin reactions (erythema, pruritus, burning) Headache Sleep disturbances (insomnia, abnormal/vivid dreams); associated with nocturnal nicotine absorption	Nasal and/or throat irritation (hot, peppery, or burning sensation) Rhinitis Tearing Sneezing Cough Headache	Mouth and/or throat irritation Cough Headache Rhinitis Dyspepsia Hiccups	Insomnia Dry mouth Nervousness/ difficulty concentrating Nausea Dizziness Constipation Rash Seizures (risk is 0.1%) Neuropsychiatric symptoms (rare; see Precautions)	Nausea Sleep disturbances (insomnia, abnormal/vivid dreams) Constipation Flatulence Vomiting Neuropsychiatric symptoms (rare; see Precautions)
Advantages	Might serve as an oral substitute for tobacco Might delay weight gain Can be titrated to manage withdrawal symptoms Can be used in combination with other agents to manage situational urges	Might serve as an oral substitute for tobacco Might delay weight gain Can be titrated to manage withdrawal symptoms Can be used in combination with other agents to manage situational urges	Once daily dosing associated with fewer compliance problems Of all NRT products, its use is least obvious to others Can be used in combination with other agents; delivers consistent nicotine levels over 24 hours	Can be titrated to rapidly manage withdrawal symptoms Can be used in combination with other agents to manage situational urges	Might serve as an oral substitute for tobacco Can be titrated to manage withdrawal symptoms Mimics hand-to-mouth ritual of smoking Can be used in combination with other agents to manage situational urges	Twice daily oral dosing is simple and associated with fewer compliance problems Might delay weight gain Might be beneficial in patients with depression Can be used in combination with NRT agents	Twice daily oral dosing is simple and associated with fewer compliance problems Offers a different mechanism of action for patients who have failed other agents
Disadvantages	Need for frequent dosing can compromise compliance Might be problematic for patients with significant dental work Proper chewing technique is necessary for effectiveness and to minimize adverse effects Gum chewing may not be acceptable or desirable for some patients	Need for frequent dosing can compromise compliance Gastrointestinal side effects (nausea, hiccups, heartburn) might be bothersome	When used as monotherapy, cannot be titrated to acutely manage withdrawal symptoms Not recommended for use by patients with dermatologic conditions (e.g., psoriasis, eczema, atopic dermatitis)	Need for frequent dosing can compromise compliance Nasal administration might not be acceptable or desirable for some patients; nasal irritation often problematic Not recommended for use by patients with chronic nasal disorders or severe reactive airway disease	Need for frequent dosing can compromise compliance Cartridges might be less effective in cold environments (≤60°F)	Seizure risk is increased Several contraindications and precautions preclude use in some patients (see Precautions) Patients should be monitored for potential neuropsychiatric symptoms^d (see Precautions)	Should be taken with food or a full glass of water to reduce the incidence of nausea Patients should be monitored for potential neuropsychiatric symptoms^d (see Precautions)

Marketed by GlaxoSmithKline.

Marketed by Pfizer.

The US Clinical Practice Guideline states that pregnant smokers should be encouraged to quit without medication based on insufficient evidence of effectiveness and theoretical concerns with safety. Pregnant smokers should be offered behavioral counseling interventions that exceed minimal advice to quit.

In July 2009, the FDA mandated that the prescribing information for all bupropion- and varenicline-containing products include a black-boxed warning highlighting the risk of serious neuropsychiatric symptoms, including changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. Clinicians should advise patients to stop taking varenicline or bupropion SR and contact a healthcare provider immediately if they experience agitation, depressed mood, and any changes in behavior that are not typical of nicotine withdrawal, or if they experience suicidal thoughts or behavior. If treatment is stopped due to neuropsychiatric symptoms, patients should be monitored until the symptoms resolve.

Abbreviations: MAO, monoamine oxidase; NRT, nicotine replacement therapy; OTC, over-the-counter (non-prescription product); Rx, prescription product.

For complete prescribing information and a comprehensive listing of warnings and precautions, please refer to the manufacturers’ package inserts.