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Nicotine (Monograph)

Brand names: Commit, Nicoderm CQ, Nicorette, Nicotrol Inhaler, Nicotrol NS
Drug class: Smoking Cessation Agents
- Smoking Deterrents
- Deterrents, Smoking
VA class: AD900

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Ganglionic (nicotinic) cholinergic-receptor agonist.a

Uses for Nicotine

Smoking Cessation

Used for nicotine replacement therapy as a temporary adjunct in the cessation of cigarette smoking either unsupervised (self-medication)188 189 190 246 257 or in conjunction with a behavior modification program under clinician supervision.1 2 5 6 7 8 9 10 11 29 30 31 96 97 191 192 193 194 195 196 244 245 257 258 263

Nicotine replacement therapy considered one of several first-line therapies by USPHS for treatment of tobacco dependence.257 For additional information, consult the most current USPHS clinical practice guideline available at [Web]

Nicotine replacement therapy provides alternative sources of nicotine that help reduce the withdrawal symptoms associated with nicotine dependence.1 2 50 78 79 80 97 101 102 103 104 Chewing the resin complex-containing gum may act as a substitute oral activity in behavior modification.5

Electronic nicotine delivery systems (ENDS) such as electronic cigarettes (e-cigarettes) have been used to aid smoking cessation attempts; however, these products are not approved by FDA for this use and evidence is limited regarding their efficacy and safety.266 267 268 269 271 272 273 The role of ENDS relative to conventional nicotine replacement therapies for smoking cessation remains to be established.266 267 271 273

Ulcerative Colitis

Transdermal nicotine has been used in the management of ulcerative colitis† [off-label].125 204 205 206 207 208 209 210

Nicotine Dosage and Administration

General

Administration

Administer nicotine percutaneously by topical application of a transdermal system.b i

Administer nicotine transmucosally by oral inhalation using a special nicotine oral inhaler or intranasally using a metered-dose spray pump. d 265 g

Administer nicotine polacrilex intrabuccally (transmucosally) as a lozenge or chewing gum.c h

May be administered as a single nicotine preparation (i.e., intrabuccally, intranasally, percutaneously, or by oral inhalation); however, if single therapy does not enable patients to quit smoking, use of transdermal nicotine may be combined with another form of nicotine replacement (i.e., either buccal nicotine polacrilex or nicotine nasal spray).257

Buccal Administration

Chewing Gum

Self-administer one piece of gum in response to the urge to smoke.1

Chew gum very slowly until a distinctive peppery taste of nicotine, minty, cinnamon, or orange taste of the gum, or a slight tingling in the mouth is perceived (typically about 15 chews);1 stop chewing gum and park between cheek and gum; once tingling is almost gone (about 1 minute), repeat chewing procedure.1 Continue for about 30 minutes or until taste dissipates.1 Do not swallow gum.1

Do not eat or drink anything other than water for 15 minutes before and during chewing of gum.1 190

Do not chew multiple pieces of gum simultaneously; do not chew too rapidly or chew pieces in succession.1 May cause excessive release of nicotine and result in adverse effects (e.g., lightheadedness, nausea, vomiting, irritation of the throat and mouth, hiccups, indigestion).1

Chew at least 9 pieces of gum daily to improve chances of quitting.c

Do not attempt to discontinue nicotine polacrilex gum therapy until craving is satisfied by 1 or 2 pieces of the gum daily, but do not continue therapy for >6 months,1 unless otherwise instructed by clinician.9 43 65

4-mg strength gum recommended in highly dependent smokers because of evidence of increased efficacy.a

Lozenges

Suck on lozenge until dissolved; do not swallow, bite, or chew.260 263 264 Allow to slowly dissolve in the mouth over 20–30 minutes, periodically moving the lozenge (e.g., with the tongue) from one side of the mouth to the other; minimize swallowing.263 264 A warm or tingling sensation may be perceived.h

Do not eat or drink anything other than water for 15 minutes before and during sucking on the lozenge.257 263 264

Use at least 9 lozenges daily for the first 6 weeks to improve chances of quitting.h

Using >1 lozenge simultaneously or using one lozenge after another in uninterrupted sequence may result in adverse effects (e.g., hiccups, heartburn, nausea).h

Self-administer lozenge in response to nicotine craving; decrease frequency of administration over time.263 264

Topical Administration

Administer percutaneously by topical application of a transdermal system once daily.b i

Apply at the same time each day, usually after awakening.101 102 103 104 129 167 188 189

Expose the adhesive surface of the system by peeling and discarding the protective liner just prior to application and apply system immediately to avoid loss of nicotine through volatilization.101 102 103 104 129

Apply transdermal system to a clean, dry, hairless area of intact skin43 101 129 on the trunk or upper outer arm101 102 103 104 129 167 188 189 by firmly pressing the system with the adhesive side touching the skin.101 129 167 Press system firmly in place with heel of hand for about 10 seconds, ensuring good contact, particularly around the edges.101 129 167 a Do not apply to sites that are oily, damaged, or irritated;43 101 129 if necessary, hair may be clipped, but do not shave area.167

System may be worn for 16 or 24 hours.b i If cravings begin upon awakening, wear patch for 24 hours.189 b If vivid dreams or sleep disruptions occur, wear patch for 16 hours; remove at bedtime and apply new patch upon awakening.189 257 b i

If system inadvertently comes off during the period of use, apply a new system; 101 102 103 104 167 a continue current application schedule or change so that the next system is applied 24 hours later.129

Rotate application sites to minimize potential skin irritation; allow ≥1 week before reusing a given site.101 102 103 129 (See Dermatologic Effects under Cautions.)

Avoid unnecessary contact with transdermal systems.101 102 103 104 Avoid touching eyes after handling; wash hands with water alone as soap may enhance percutaneous absorption.101 102 103 104 167

Intranasal Administration

Administer intranasally using a metered-dose spray pump.191

Prime spray pump prior to initial use by spraying into a tissue until a fine spray is seen (6–8 times); discard tissue.d

If spray pump is not used for 24 hours, reprime pump by spraying into a tissue 1–2 times.d

Clear nasal passages prior to administration.d

Tilt the head back slightly;191 d insert tip of bottle into one nostril as far as is comfortable.d Breathe through the mouth and spray once into nostril; do not sniff, swallow, or inhale through the nose while administering.191 Repeat this procedure for the other nostril.d

If nose runs, sniff gently to keep nasal spray in nose; wait 2–3 minutes before blowing nose.d

Avoid contact with skin, eyes, and mouth; if contact occurs, rinse with plain water immediately.d If intranasal bottle breaks, wear protective gloves, wipe with paper towels, and wash surfaces thoroughly.d

Oral Inhalation

Administer transmucosally as an inhaled vapor by oral inhalation using a special nicotine oral inhaler that mimics smoking cigarettes.244 245 246 247 248

Hold the oral inhaler with two hands; separate the top and bottom pieces by pushing and turning the pieces until markings line up.g Insert one nicotine cartridge and push the cartridge until it pops into place.g Line up markings on the top and bottom pieces of the inhaler and push pieces together tightly; lock inhaler by turning pieces until markings do not line up.g

Place the mouthpiece of the inhaler between lips and puff on the inhaler using rapid shallow sucking (“buccal mode”);244 248 alternatively, inhale slowly and deeply into back of throat (“pulmonary mode”).248 g Nicotine is vaporized and absorbed in mouth and throat.g (See Absorption under Pharmacokinetics.) Shallow puffing method generally is preferred.244 248 250 Deep inhalation technique requires considerable effort and does not result in substantially increased drug delivery or other benefits.248

Individualize orally inhaled dosage to the level of nicotine replacement required; optimum results generally achieved by frequent continuous puffing of the inhaler over 20 minutes.244

Nicotine is used up from cartridge after about four 5-minute sessions or one 20-minute session of active puffing.250

When cartridge is empty, remove top of mouthpiece; discard empty cartridge away from children and pets.g Store with mouthpiece in locked position and cartridges in plastic case.g Clean reusable mouthpiece regularly with soap and water.244

Use inhaler at temperatures >60°F; cold temperatures decrease the amount of nicotine inhaled.g

Also administered transmucosally as an inhaled vapor by oral inhalation via electronic nicotine delivery systems (ENDS) such as e-cigarettes and vape pens; however, safety and efficacy in smoking cessation not evaluated by FDA.266 267 273

Dosage

Chewing gum and lozenges available as nicotine polacrilex; dosage expressed in terms of nicotine.1 264

Nicotine oral inhaler cartridges labeled as containing 10 mg of nicotine deliver ≤4 mg total with repeated inhalation.244 247 250 The amount of nicotine released depends on the volume and temperature of the air passing through the inhaler.244 245 246 247 248 An intensive inhalation regimen (80 deep inhalations over 20 minutes) releases approximately 4 mg of nicotine.265

Metered nasal spray delivers 0.5 mg of the nicotine per metered spray and about 200 sprays (i.e., 100 doses) per 100-mg container.191

Adults

Smoking Cessation
Buccal (Chewing Gum)

Patients who smoke <25 cigarettes daily: Chew a 2-mg piece of gum every 2 hours during weeks 1–6; chew a 2-mg piece every 2–4 hours during weeks 7–9; and chew a 2-mg piece every 4–8 hours during weeks 10–12 of therapy.c Alternatively, chew a 2-mg piece of gum whenever the urge to smoke occurs; do not exceed 2 pieces (4 mg) per hour.1

Patients who smoke ≥25 cigarettes daily: Chew a 4-mg piece of gum every 2 hours during weeks 1–6; chew a 4-mg piece every 2–4 hours during weeks 7–9; and chew a 4-mg piece every 4–8 hours during weeks 10–12 of therapy.c Alternatively, chew a 4-mg piece whenever the urge to smoke occurs; do not exceed 2 pieces (8 mg) per hour.1

Taper dosage by chewing each piece for only 10–15 minutes and gradually reducing the number of pieces chewed, or chew each piece for longer than 30 minutes but reduce the total pieces per day, or substitute regular chewing gum for some pieces.c

Buccal (Lozenges)

Patients who smoke first cigarette >30 minutes after waking: One 2-mg lozenge every 1–2 hours during weeks 1–6; then one 2-mg lozenge every 2–4 hours during weeks 7–9; and one 2-mg lozenge every 4–8 hours during weeks 10–12.263 264 h

Patients who smoke first cigarette ≤30 minutes after waking: One 4-mg lozenge every 1–2 hours during weeks 1–6; then one 4-mg lozenge every 2–4 hours during weeks 7–9; and one 4-mg lozenge every 4–8 hours during weeks 10–12.263 264 h

Do not exceed 5 lozenges in 6 hours or 20 lozenges daily.263 264

Discontinue therapy if mouth problems, persistent indigestion, severe sore throat, irregular heartbeat, palpitations, or symptoms suggestive of overdosage (nausea, vomiting, dizziness, diarrhea, weakness, and rapid heartbeat) develop.264

Transdermal

Patients who smoke ≤10 cigarettes daily: Initially, 14 mg daily for 6 weeks, then 7 mg daily for 2 weeks, then discontinue.189 b i

Patients who smoke >10 cigarettes daily: Initially, 21 mg daily for 4–6 weeks; then 14 mg daily for 2 weeks; then 7 mg daily for 2 weeks; then discontinue therapy.189 b i

Intranasal

Initially, 1–2 sprays (0.5–1 mg) in each nostril per hour (1–2 mg per hour total); may increase up to a maximum of 5 sprays (5 mg) in each nostril per hour (10 mg total) or a maximum total of 80 sprays (40 mg) daily.191 e

Initially, use at least 16 sprays (8 mg total) daily to increase chance of efficacy.191 Then, individualize dosage based on nicotine dependence and occurrence of symptoms of nicotine excess.191

Continue treatment in successfully abstinent patients for up to 8 weeks then discontinue over 4–6 weeks.191

Taper dosage by using only 1 spray at a time, using the spray less frequently, keeping a tally of daily usage, trying to meet a steadily reducing usage target, skipping a dose by not medicating every hour, or setting a planned “quit date” for stopping use of the spray.191 Some patients may not require tapering.191

Oral Inhalation

Initially, 6–16 cartridges daily for up to 12 weeks, then gradually decrease daily dosage over 6–12 weeks.244 245 246

Use ≥6 cartridges daily for the first 3–6 weeks to increase chance of efficacy.244 Individualize dosage based on nicotine dependence and occurrence of symptoms of nicotine excess.244

Taper dosage by using less frequently, keeping a tally of daily usage, trying to meet a steadily reducing usage target, or setting a planned “quit date” for stopping use of the inhaler.265 Some patients may not require tapering.265

Prescribing Limits

Adults

Smoking Cessation
Buccal (Chewing Gum)

Maximum 2 pieces of 2-mg gum per hour (i.e., maximum 24 pieces [48 mg nicotine] daily).c Maximum 12 weeks of therapy.c

Maximum 2 pieces of 4-mg gum per hour (i.e., maximum 24 pieces [96 mg nicotine] daily).c Maximum 12 weeks of therapy.c

Clinician supervised: Maximum 30 pieces of 2-mg gum daily (i.e., 60 mg nicotine) or 24 pieces of 4-mg gum daily (i.e., 96 mg nicotine).1 190 195

Buccal (Lozenges)

Maximum 5 lozenges in 6 hours or 20 lozenges daily.h Maximum 12 weeks of therapy.h

Transdermal

Patients who smoke ≤10 cigarettes daily: Maximum 8 weeks of therapy.b

Patients who smoke >10 cigarettes daily: Maximum 10 weeks of therapy.b

Continued therapy for periods longer than usually recommended may be appropriate for certain patients to promote extended abstinence.257 Continuation of therapy >12 weeks not recommended by manufacturer.101 102 103 104

Intranasal

Maximum 5 sprays (5 mg) in each nostril per hour (maximum 10 mg total) or a maximum total of 80 sprays (40 mg) daily.191 257 e

Manufacturer states that continuing therapy >12 weeks does not improve outcome.e Safety of continuing therapy >6 months not established.e

Oral Inhalation

Maximum 16 cartridges daily for up to 12 weeks.265

Manufacturer states that safety of continuing therapy >6 months not established.265

Special Populations

No special population dosage recommendations at this time.a b

Detailed Nicotine dosage information

Cautions for Nicotine

Contraindications

Warnings/Precautions

Warnings

Nicotine Toxicity

Risk of nicotine toxicity (e.g., nausea, hypersalivation, abdominal pain, vomiting, diarrhea, perspiration, headache, dizziness, hearing and visual disturbances, mental confusion, weakness)1 4 36 97 191 244 and addiction.101 102 103 104 244 Sustained use of nicotine preparations is not recommended.1 81 101 102 103 104 244 Weigh risk of nicotine replacement against hazard of continued smoking concurrent with nicotine replacement therapy and likelihood of smoking cessation without nicotine replacement.101 102 103 104 244

Discontinue nicotine polacrilex lozenges if symptoms suggestive of overdosage (nausea, vomiting, dizziness, diarrhea, weakness, and rapid heartbeat) occur.264

Fetal/Neonatal Morbidity

Animal studies indicate fetal harm; pregnant women should attempt smoking cessation with educational and behavioral interventions before considering nicotine therapy.1 101 102 103 104 128 191 194 195 196 244 257 264 e

Use during pregnancy only if the increased likelihood of smoking cessation justifies potential risk to the fetus and patient of nicotine replacement and possible continued smoking.1 101 102 103 104 128 191 194 195 196 244 264 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.e 265

General Precautions

Respiratory Effects

Possible exacerbation of bronchospasm.244 Use oral inhaler with caution in patients with bronchospastic disease;244 other dosage forms may be preferable.244

Intranasal nicotine is not recommended in patients with severe reactive airway disease.191

Nasopharyngeal Effects

Nicotine nasal spray may irritate nasal mucosa;e use of nasal spray not recommended in patients with a history of chronic nasal disorders (e.g., allergy, rhinitis, polyps, sinusitis).191

Discontinue nicotine polacrilex lozenges if severe sore throat occurs.264

Cardiovascular Effects

Possible increased risk of adverse cardiovascular effects;144 149 164 165 211 212 213 214 215 however, causal relationship between nicotine replacement therapy and cardiac complications not established.101 102 103 104 144 148 149 191 244

Discontinue therapy if irregular heartbeat or palpitations occur.264 b c h i

Use with caution and only after careful evaluation in patients with coronary heart disease (i.e., history of MI, angina pectoris), serious cardiac arrhythmias, or vasospastic diseases (e.g., Buerger's disease, Prinzmetal's variant angina, Raynaud's phenomena).101 102 103 104 144 148 149 191 244 Benefit of nicotine replacement therapy must outweigh risks of continued cigarette smoking.43 257

Self-medication not recommended in patients in the immediate post-MI period, with serious arrhythmias, or with severe or worsening angina.188 189 190

Endocrine Effects

Possible hyperinsulinemia and insulin resistance with prolonged nicotine replacement therapy.254 Use with caution in hyperthyroidism, pheochromocytoma, or insulin-dependent diabetes.101 102 103 104 191 244

GI Effects

Possible delayed healing of peptic ulcer disease; use with caution.101 102 103 104 191 244

Discontinue nicotine polacrilex lozenges if persistent indigestion develops.264

Use nicotine polacrilex gum with caution in patients with a history of esophagitis.1 97

Hypertension

Possible increased risk of malignant hypertension in patients with accelerated hypertension; use with caution in such patients.1 101 102 103 104 191 244

Possible perpetuation of hypertension; use with caution in patients with systemic hypertension.a

Nicotine Dependence

Transference of dependence on nicotine may occur;1 81 87 88 90 96 97 98 191 195 244 257 potential for abuse and dependence on nicotine nasal spray appears to be greater than that for other formulations of nicotine (i.e., nicotine polacrilex gum, transdermal nicotine systems) but less than that of cigarettes.191 196 201 202 257

To minimize withdrawal symptoms87 and the risk of dependence on nicotine, withdraw gradually or discontinue use of nicotine polacrilex gum or transdermal or intranasal nicotine after 2–3 months of therapy.1 2 3 36 191 195 244

Concern exists regarding possible risk of nicotine dependence transference from use of electronic nicotine delivery systems (ENDS) such as e-cigarettes and vape pens in individuals, particularly adolescents, not previously dependent on nicotine but who subsequently transition to actual cigarette use.267 268 270 272 273

Phenylketonuria

Commit nicotine polacrilex lozenges contain aspartame (NutraSweet), which is metabolized in the GI tract to provide 3.4 mg of phenylalanine per lozenge.264

Oral and Dental Effects

Risk of occlusal stress when nicotine polacrilex gum is chewed for long periods of time; may result in displaced dental restorations or loosening of dental inlays or fillings.1 72 Gum may stick to dentures, dental caps, or partial bridges; if excessive sticking or damage to dental work occurs, discontinue gum and consult clinician.1

Use nicotine polacrilex gum with caution in patients with a history of oral or pharyngeal inflammation, or dental conditions exacerbated by chewing gum.1 97

Discontinue nicotine polacrilex lozenges if mouth problems develop.264

Dermatologic Effects

Possible skin reactions (e.g., urticaria, hives, rash) with transdermal systems.101 102 103 104 129 Increased risk of such reactions in patients with some dermatologic conditions (e.g., psoriasis, atopic or eczematous dermatitis).101 102 103 104

If skin reaction occurs, discontinue transdermal system and contact clinician;101 102 103 104 129 topical corticosteroids and/or oral antihistamines recommended.43 112 144 149 195

Risk of contact sensitization with transdermal systems; serious reaction may occur with re-exposure to smoking or other nicotine products.101 102 103 104

Nervous System Effects

Potential adverse nervous system effects (e.g., insomnia,1 102 136 137 headache,1 68 101 102 103 104 109 111 118 137 244 246 263 dizziness, lightheadedness).1 27 104 109

Specific Populations

Pregnancy

Category D.e 265 (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Distributed into milk.1 34 70 73 101 102 103 104 191 244 Use caution.1 34 70 73 101 102 103 104 191 244

Weigh risk of exposure to nicotine in drug versus risk of nicotine and other components of tobacco smoke from cigarettes.1 101 102 103 104 191 244

Pediatric Use

Safety and efficacy not established.1 101 102 103 104 191 196 244

Use or ingestion of used or unused nicotine replacement systems by children may cause poisoning or be fatal; keep used and unused containers out of reach of children.101 102 103 104 191 244

Risk of choking if nicotine oral inhalers are swallowed; keep out of reach of children.244

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults;101 102 103 104 244 select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease.e 265

Hepatic Impairment

Not studied in patients with hepatic impairment; use with caution.101 102 103 104 244

Renal Impairment

Not studied in patients with renal impairment; clearance may be decreased in patients with severe renal impairment.44 101 102 103 104 244

Common Adverse Effects

Buccal therapy (gum): Indigestion;1 7 27 85 96 257 nausea;1 6 9 27 68 85 95 hiccups;1 7 68 89 94 96 traumatic injury to oral mucosa and/or teeth;1 68 irritation and/or tingling of the tongue, mouth, and throat;1 5 9 27 29 68 85 89 95 96 oral mucosal ulceration;1 5 6 7 29 68 89 96 jaw-muscle ache;1 5 6 7 29 68 eructation;1 68 95 gum sticking to teeth;89 unpleasant taste;5 85 95 dizziness;1 27 lightheadedness;1 27 headache;1 68 insomnia.1

Buccal therapy (lozenges): Nausea,263 dyspepsia,263 flatulence,263 headache,263 upper respiratory tract infections.263

Transdermal therapy: Application site reactions (i.e., pruritus, burning, or erythema),101 102 103 104 113 114 115 118 126 136 137 195 diarrhea,101 102 dyspepsia,103 137 abdominal pain,103 dry mouth.101 102 109 137

Intranasal therapy: Runny nose,191 196 202 203 throat irritation,191 196 201 202 203 watery eyes,191 196 201 202 203 sneezing,191 196 201 202 203 cough.191 196 201 202 203

Oral inhalation therapy: Dyspepsia,244 246 oropharyngeal irritation (e.g., coughing, mouth and throat irritation),244 245 246 rhinitis,244 headache.244 246

Drug Interactions

Cigarette smoke57 93 and nicotine induce hepatic enzymes.34 53 57

Smoking Cessation

Cessation of smoking may alter the response to concomitant administration of various drugs in patients who previously smoked.1 93 191 244

Potential pharmacokinetic interaction (decreased metabolism and increased blood concentrations of certain drugs) with cessation of smoking.1 34 93

Consider the effect of smoking cessation in patients receiving nicotine replacement therapy when patient is receiving other drugs concomitantly.43 44 101 102 103 104 191 244

Sympathomimetic and Sympatholytic Drugs

Potential pharmacodynamic interaction (increased circulating plasma concentrations of cortisol and catecholamines); may require dosage adjustment of sympathomimetic (adrenergic) or sympatholytic (adrenergic blocking) drugs.1

Possible altered absorption of transdermal nicotine from drugs producing cutaneous vasoconstriction (e.g., sympathomimetic agents) or vasodilation (e.g., antihypertensive agents).45

Foods Affecting Salivary Acidity

Transient decrease of salivary pH may inhibit buccal absorption of nicotine from gum, lozenge, or oral inhaler.100 257

Specific Drugs and Foods

Drug or Food

Interaction

Comments

Acetaminophen

Smoking cessation may decrease metabolism and increase blood concentrations of acetaminophene

Decrease dosage of acetaminophen as requirede

Acidic beverages (e.g., coffee, juices, carbonated soft drinks)

May inhibit buccal absorption of nicotine from gum, lozenge, or orally inhaled drug100 257 h

Do not eat or drink for 15 minutes before and during gum or lozenge therapy1 100 257 h

Adrenergic agonists (e.g., isoproterenol, phenylephrine)

Smoking cessation may decrease circulating plasma concentrations of catecholamines1

Increase dosage of adrenergic agonists as requirede

Adrenergic antagonists (e.g., prazosin, labetalol)

Smoking cessation may decrease circulating plasma concentrations of catecholamines1

Decrease dosage of adrenergic antagonists as requirede

β-Adrenergic blocking agents (e.g., propranolol)

Smoking cessation may decrease metabolism and increase blood concentrations of β-adrenergic blocking agents1 34 57 93 191 244

Smoking cessation may restore the decreased cardiac output and hypotensive effect induced by propranolol1 57 191

Decrease dosage of β-adrenergic blocking agent as requirede

Bupropion

Possible increased risk of hypertension240

May be used concomitantly with transdermal nicotine therapy240

Caffeine

Smoking cessation may decrease metabolism and increase blood concentrations of caffeine1 34 57 93 191 244

Decrease dosage of caffeine as requirede

Furosemide

Smoking cessation may increase diuretic effects of furosemide1 57 191

Glutethimide

Smoking cessation may decrease absorption of glutethimide1 57

Insulin

Smoking cessation increases absorption of subcutaneous insulin191

Monitor blood glucose closely; adjust insulin dosage as needede

Nasal vasoconstrictors (e.g., xylometazoline)

Delays time to peak plasma concentration of nicotine nasal spray191

Oxazepam

Smoking cessation may decrease metabolism and increase blood concentrations of oxazepam1 34 57 93 191 244

Decrease dosage of oxazepam as required1 34 57 93 191 244

Pentazocine

Smoking cessation may decrease metabolism and increase blood concentrations of pentazocine1 34 57 93 191 244

Decrease dosage of pentazocine as required1 34 57 93 191 244

Propoxyphene

Smoking cessation may decrease metabolism of propoxyphene1 57

Decrease dosage of propoxyphene as required1 57

Theophylline

Smoking cessation may decrease metabolism and increase blood concentrations of theophylline1 34 57 93 191 244

Monitor plasma concentrations and adjust dosage of theophylline as required93

Tricyclic antidepressants (e.g., imipramine)

Smoking cessation may decrease metabolism and increase blood concentrations of tricyclic antidepressants1 34 57 93 191 244

Adjust dosage of tricyclic antidepressant as requirede 265
Nicotine drug interactions (more detail)

Nicotine Pharmacokinetics

Absorption

Bioavailability

Readily absorbed transmucosally following intrabuccal administration via chewing gum or sucking a lozenge,1 2 5 25 27 28 94 97 and following oral inhalation196 244 247 248 249 251 and intranasal administration;191 absorbed minimally from the GI tract.4 5 12 97 196

Readily absorbed percutaneously following topical application of a transdermal system.101 102 103 104 108 109 120

Gum: Averages 53–55%,94 95 with peak concentrations achieved within 25–30 minutes.44 102 119 142 147 151 196 244 246 247 252

Lozenge: Approximately 25–27% more of an equivalent dose absorbed with lozenge than with gum.263

Transdermal: Approximately 68–98%,101 102 103 104 108 109 120 with peak concentrations achieved within 2–10 hours.44 102 119 142 147 151 196 244 246 247 252

Intranasal: Approximately 53%,191 with peak concentrations achieved within 4–15 minutes.44 102 119 142 147 151 196 244 246 247 252

Oral inhalation: Approximately 60%,248 mostly absorbed in the mouth,244 248 249 251 with peak concentrations achieved within 15–30 minutes.44 102 119 142 147 151 196 244 246 247 252

Food

Acidic beverages may interfere with buccal absorption.1 100 (See Specific Drugs and Foods under Interactions.)

Plasma Concentrations

Gum: Relatively constant blood nicotine concentrations attained following repeated administration are similar to those produced by smoking cigarettes.2 5 27

Transdermal: Plasma nicotine concentrations generally lower and fluctuate less than those produced by smoking cigarettes.123 144

Intranasal: Plasma nicotine concentrations similar to those produced by smoking cigarettes.152 153 154 191 252

Oral inhalation: Lower plasma nicotine concentrations compared with nasal spray.196 246

Special Populations

Common cold or rhinitis may decrease extent of absorption and peak plasma concentrations of intranasal nicotine.191

Obesity decreases peak plasma concentration and AUC of transdermal systems.44 102 104 176

Distribution

Extent

Following IV administration in animals, rapidly distributes into most body tissues and fluids with highest concentrations in the cerebral cortex12 32 60 and adrenal medulla,60 and lower concentrations in spleen, adrenal cortex, kidney, and pancreas.60

Nicotine crosses the placenta14 70 97 and is distributed into milk.101 102 103 104

Plasma Protein Binding

<5%.191 244

Elimination

Metabolism

Rapidly and extensively metabolized, principally in the liver, to >20 primarily inactive metabolites.4 12 34 40 56 97 191 244

Elimination Route

Excreted in urine mainly as metabolites (70–90%) and as unchanged drug (10–30%).1 244 265 e

Half-life

Biphasic;12 terminal half-life averages 2 hours (range: 1–4 hours).1 4 12 38 39 43 45 97 101 102 103 104 171 172 244

Following removal of a transdermal system, apparent half-life averages 3–6 hours.20 101 102 103 104 106 107 108 109 142 144 146 150 151

Special Populations

Hepatic impairment may reduce clearance.101 102 103 104 244

Severe renal failure may reduce clearance.44 101 102 103 104 244

Stability

Storage

Oral

Gum

<30°C; protect from light.1

Lozenge

20–25°C; protect from light.264

Transdermal

20–25°C in unopened, protective pouch.b

Intranasal

Solution

<30°C.191

Oral Inhalation

<30°C; protect cartridges from light.244 250

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Nicotine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Nasal

Solution

0.5 mg/metered spray

Nicotrol NS

Pfizer

Oral Inhalation

Inhalant

4 mg/metered spray

Nicotrol Inhaler

Pfizer

Topical

Transdermal System

7 mg/24 hours*

NicoDerm CQ Step 3

GlaxoSmithKline

Nicotine Transdermal System

14 mg/24 hours*

NicoDerm CQ Step 2

GlaxoSmithKline

Nicotine Transdermal System

21 mg/24 hours*

NicoDerm CQ Step 1

GlaxoSmithKline

Nicotine Transdermal System

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Nicotine Polacrilex

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Buccal (Transmucosal)

Lozenges

2 mg (of nicotine)*

Commit

GlaxoSmithKline

Nicotine Polacrilex Lozenge

4 mg (of nicotine)*

Commit

GlaxoSmithKline

Nicotine Polacrilex Lozenge

Pieces, chewing gum

2 mg (of nicotine)*

Nicorette

GlaxoSmithKline

Nicotine Polacrilex Gum

4 mg (of nicotine)*

Nicorette DS

GlaxoSmithKline

Nicotine Polacrilex Gum

AHFS DI Essentials™. © Copyright 2025, Selected Revisions March 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. SmithKline Beecham. Nicorette and Nicorette DS (double strength) (nicotine polacrilex) prescribing information and patient information dated 1993 Nov. In: Physicians’ desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:2458-62.

2. Merrell Dow Pharmaceuticals Inc. Questions and answers about nicotine gum. Cincinnati, OH; [undated].

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