Table 2 FDA-approved medications for smoking cessation.

Nicotine Replacement Therapy (NRT) FormulationsBupropion SRVarenicline
GumLozengeTransdermal PatchNasal SprayOral Inhaler
ProductNicorette1, Generic
OTC 2 mg, 4 mg
original, cinnamon,
fruit, mint
Nicorette1, Generic
Nicorette1 Mini OTC
2 mg, 4 mg;
cherry, mint
NicoDerm CQ1,
Generic
OTC (NicoDerm
CQ, generic)
7 mg, 14 mg, 21 mg
(24-hr release)
Nicotrol NS2 Rx
Metered spray
10 mg/mL nicotine
solution
Nicotrol Inhaler2 Rx
10 mg cartridge
delivers 4 mg
inhaled vapor
Zyban1, Generic Rx
150 mg sustained-
release tablet
Chantix2
Rx 0.5 mg, 1 mg
tablet
Precautions
  • Recent (≤ 2 weeks) myocardial infarction

  • Serious underlying arrhythmias

  • Serious or worsening angina pectoris

  • Temporomandibular joint disease

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Recent (≤ 2 weeks) myocardial infarction

  • Serious underlying arrhythmias

  • Serious or worsening angina pectoris

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Recent (≤ 2 weeks) myocardial infarction

  • Serious underlying arrhythmias

  • Serious or worsening angina pectoris

  • Pregnancy3 and breastfeeding

  • Adolescents (<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

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Recent (≤ 2 weeks) myocardial infarction

  • Serious underlying arrhythmias

  • Serious or worsening angina pectoris

  • Bronchospastic disease

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Concomitant therapy with medications/conditions known to lower the seizure threshold

  • Hepatic impairment

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Treatment-emergent neuropsychiatric symptoms4 Boxed warning removed 12/2016

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

  • Severe renal impairment (dosage adjustment is necessary)

  • Pregnancy3 and breastfeeding

  • Adolescents (<18 years)

  • Treatment-emergent neuropsychiatric symptoms4

    Boxed warning removed 12/2016

Dosing1st 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

1st 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)

  • 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 x
4–6 weeks
14 mg/day x 2 weeks
7 mg/day x 2 weeks
≤10 cigarettes/day:
14 mg/day x 6 weeks
7 mg/day x 2 weeks
  • Rotate patch application site daily; do not apply a new patch to the same skin site for at least one week

  • 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 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 x 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

  • May initiate up to 35 days before target quit date OR may reduce smoking over a 12-week period of treatment prior to quitting and continue treatment for an additional 12 weeks

Adverse
Effects
  • Mouth and throat irritation

  • Jaw muscle soreness

  • Hiccups

  • GI complaints (dyspepsia, nausea)

  • May stick to dental work

  • Mouth and throat irritation

  • Hiccups

  • GI complaints (dyspepsia, nausea)

  • Local skin reactions (erythema, pruritus, burning)

  • Sleep disturbances (abnormal or vivid dreams, insomnia); associated with nocturnal nicotine absorption

  • Nasal and/or throat irritation (hot, peppery, or burning sensation)

  • Ocular irritation/ tearing

  • Sneezing

  • Cough

  • Mouth and/or throat irritation

  • Cough

  • Hiccups

  • GI complaints (dyspepsia, nausea)

  • Insomnia

  • Dry mouth

  • Nausea

  • Anxiety/difficulty concentrating

  • Constipation

  • Tremor

  • Rash

  • Seizures (risk is 0.1%)

  • Neuropsychiatric symptoms (rare; see Precautions)

  • Nausea

  • Sleep disturbances (insomnia, abnormal/vivid dreams)

  • Headache

  • Flatulence

  • Constipation

  • Taste alteration

  • Neuropsychiatric symptoms (rare; see Precautions)

  • Adverse effects more commonly experienced when chewing the lozenge or using incorrect gum chewing technique (due to rapid nicotine release):

    • Lightheadedness/dizziness

    • Nausea/vomiting

    • Hiccups

    • Mouth and throat irritation

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

  • Relatively inexpensive

  • 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

  • Relatively inexpensive

  • Once-daily dosing associated with fewer adherence 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

  • Relatively inexpensive

  • 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 adherence problems

  • Might delay weight gain

  • Might be beneficial in patients with depression

  • Can be used in combination with NRT agents

  • Relatively inexpensive (generic formulations)

  • Twice-daily oral dosing is simple and associated with fewer adherence problems

  • Offers a different mechanism of action for patients who have failed other agents

  • Most effective cessation agent when used as monotherapy

Disadvantages
  • Need for frequent dosing can compromise adherence

  • Might be problematic for patients with significant dental work

  • Proper chewing technique is necessary for effectiveness and to minimize adverse effects

  • Gum chewing might not be acceptable or desirable for some patients

  • Need for frequent dosing can compromise adherence

  • 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 adherence

  • 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

  • Cost of treatment

  • Need for frequent dosing can compromise adherence

  • Cartridges might be less effective in cold environments (≤60°F)

  • Cost of treatment

  • Seizure risk is increased

  • Several contraindications and precautions preclude use in some patients (see Precautions)

  • Patients should be monitored for potential neuropsychiatric symptoms4 (see Precautions)

  • Patients should be monitored for potential neuropsychiatric symptoms4 (see Precautions)

  • Cost of treatment

Cost/day52 mg or 4 mg:
$1.90–$3.60
(9 pieces)
2 mg or 4 mg:
$3.33–$3.60
(9 pieces)
$1.52–$2.90
(1 patch)
$8.72
(8 doses)
$14.88
(6 cartridges)
$2.58–$8.25
(2 tablets)
$15.14
(2 tablets)

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

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

Copyright © 1999-2019 The Regents of the University of California. All rights reserved. Updated January 9, 2019.

1Marketed by GlaxoSmithKline.

2Marketed by Pfizer.

3The U.S. 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.

4In 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 health care provider immediately if they experience agitation, depressed mood, or 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. Based on results of a mandated clinical trial, the FDA removed this boxed warning in December 2016.

5Approximate cost based on the recommended initial dosing for each agent and the wholesale acquisition cost from Red Book Online. Thomson Reuters, December 2018.