Nicotine

Pronunciation

Class: Autonomic Drugs, Miscellaneous
VA Class: AD900
Chemical Name: S-3-(1-Methyl-2-pyrrolidinyl)pyridine
Molecular Formula: C10H14N2• x(C10H10•C4H6O2)x
CAS Number: 54-11-5
Brands: Nicotrol NS, Nicotrol Inhaler, Nicoderm CQ, Commit, Nicorette

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

Slideshow: COPD: Could You Be At Risk?

Nicotine replacement therapy considered first-line therapy by USPHS for treatment for dependence on tobacco.257

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

Ulcerative Colitis

Transdermal nicotine has been used in the management of ulcerative colitis.125 204 205 206 207 208 209 210

Nicotine Dosage and Administration

General

  • To increase smoking cessation rate,101 144 194 195 196 use as part of a comprehensive program of multiple treatment strategies, including behavioral modification.43 44 101 102 103 104 115 116 119 126 131 144 148 149 167 193 194 195 196 257 258 a

  • Individualize duration of therapy based on patient response and degree of nicotine dependence.1 190 257 263 264 a

  • Stop smoking prior to initiating nicotine replacement therapy;1 190 257 263 264 self-medication not recommended in patients who continue to smoke, chew tobacco, or use snuff or other nicotine-containing preparations.188 189 190

  • Discontinue therapy in patients who continue to smoke 4 weeks after initiating treatment;101 102 103 104 may use nicotine replacement therapy again in subsequent attempts to quit smoking.101 102 103 104 121

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.1 257 Continue for about 30 minutes or until taste dissipates.1 257 Do not swallow gum.1

Do not eat or drink anything other than water for 15 minutes before and during chewing of gum.1 190 257

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 dissolve slowly 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.101 102 103 104 129 167 188 189 257

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 102 103 104 129 167 188 189 257 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;191 257 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.191 257 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”);244 248 257 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.244 248 250 257 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

Dosage

Chewing gum and lozenge 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.244 247 250 257 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 nicotine per metered spray and about 200 sprays (i.e., 100 doses) per 100-mg container.191 257

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 once 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.189 257 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.191 257 e

Initially, use at least 16 sprays (8 mg total) daily to increase chance of efficacy.191 257 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.244 245 246 257

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

Cautions for Nicotine

Contraindications

  • Known hypersensitivity to nicotine, menthol (oral inhaler), or any ingredient in the formulation.101 102 103 104 191 244

  • Nicotine polacrilex gum in patients with temporomandibular joint disease.101 102 103 104 191 244 (See Oral and Dental Effects under Cautions.)

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.1 101 102 103 104 128 191 194 195 196 244 257 264 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.191 257

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).191 257

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.101 102 103 104 144 148 149 191 244 257

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).101 102 103 104 144 148 149 191 244 257 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 arhythmias, 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; 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

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 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 73 101 102 103 104 191 244 257 Use caution.1 34 70 73 101 102 103 104 191 244 257

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 However, the USPHS states that nicotine replacement therapy may be considered in adolescents when there is evidence of nicotine dependence and a desire to quit the use of tobacco.196 257

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 96 257 traumatic injury to oral mucosa and/or teeth;1 68 257 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 (lozenge): Nausea,263 dyspepsia,263 flatulence,263 headache,263 upper respiratory tract infections.263

Transdermal therapy: Application site reactions (i.e., pruritus, burning, or erythema),101 102 103 104 113 114 115 118 126 136 137 195 257 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),244 245 246 257 rhinitis,244 257 headache.244 246

Interactions for Nicotine

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

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 antagonize 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 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 cigarette.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 nicotine administered as 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

  • A ganglionic (nicotinic) cholinergic-receptor agonist;1 4 34 50 97 169 171 exhibits stereospecific binding to receptors in autonomic ganglia, the adrenal medulla, the neuromuscular junction, and the brain.1 4 34 43 97 101 102 103 104 169 170 171 172

  • Exhibits both stimulant (e.g., marked CNS and respiratory stimulation) and depressant effects in the CNS and peripheral nervous system.1 4 34 43 50 97 172

  • Behavior-reinforcing properties of nicotine result from dose-related effects on the CNS.e 265

  • Low doses produce stimulant effects (e.g., increased alertness and cognitive performance) in the cerebral cortex1 101 102 103 104 169 171 173 174 175 by stimulating autonomic ganglia and facilitating neurotransmission.4 97

  • High doses produce reward effects mediated through the mesolimbic dopaminergic system,1 101 102 103 104 169 171 173 174 175 with initial ganglionic stimulation, which is quickly followed by inhibition of neurotransmission.4 97

  • Activates neurohormonal pathways, releasing acetylcholine, norepinephrine, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, and ACTH.e 265

  • Cardiovascular effects mediated principally via stimulation of sympathetic ganglia and the adrenal medulla and via release of catecholamines from neuronal tissue.4 34 43 50 172 Low doses produce peripheral vasoconstriction and increase heart rate, myocardial contractile force, cardiac output, stroke volume, velocity of myocardial contraction, and BP, resulting in an increase in cardiac work and oxygen consumption;1 4 34 171 172 however, large doses may cause hypotension.1 4 172

  • GI effects mediated principally via cholinergic stimulation;4 results in increased tone and motor activity of GI smooth muscle.4 Systemic absorption may cause nausea, vomiting, and diarrhea.4 97

  • Chronic use may result in psychologic and physical dependence; tolerance to some of the pharmacologic effects may occur.1 2 12 34 50 97

Advice to Patients

  • Importance of not smoking or using other tobacco products during nicotine replacement therapy.1 190 257 263 264

  • Advise patient of improved smoking cessation success with a comprehensive treatment approach (e.g., support groups, counseling, specific behavior change techniques).g

  • Importance of providing patient a copy of the manufacturer's patient information.1 190 264 When used for self-medication, importance of reading patient instructions provided by the manufacturer.b c h i

  • Importance of patient understanding the proper use (see Administration under Dosage and Administration) and disposal of nicotine preparations.b c d e 265 g h i

  • Importance of avoiding unnecessary contact with transdermal systems.101 102 103 104 Advise patients to discard transdermal system carefully; fold so adhesive side sticks to itself, place in empty protective pouch, and dispose of immediately.101 102 103 104 129 264 Importance of washing hands with water alone; importance of not touching eyes prior to handwashing.43 101 102 103 104 129 167

  • Importance of keeping used and unused transdermal systems, intranasal containers, oral inhaler cartridges, gum, and lozenges out of the reach of children and pets.1 101 102 103 104 191 244 264 Importance of contacting clinician or poison control immediately if a child or pet chews or swallows a nicotine product.1 101 102 103 104 191 244 264

  • Importance of calling clinician or poison control center if symptoms of nicotine overdose occur (e.g., bad headaches, dizziness, upset stomach, drooling, vomiting, diarrhea, cold sweat, blurred vision, hearing difficulties, mental confusion, weakness, fainting).d g

  • Advise patients of symptoms of nicotine withdrawal (e.g., craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints [headache, myalgia, constipation, fatigue], weight gain).265 e h

  • For transdermal therapy, importance of consulting clinician before initiating therapy if patient has a dermatologic condition or is allergic to adhesive tape.188 189 (See Dermatologic Effects under Cautions.) Importance of discontinuing use and contacting clinician if severe or persistent skin reaction occurs at transdermal site (e.g., severe erythema, pruritus, edema).101 102 103 104 129

  • Advise patients receiving nicotine polacrilex gum that chewing gum too rapidly may result in lightheadedness, nausea, vomiting, irritation of throat and mouth, hiccups, and indigestion.1

  • Advise patients receiving intranasal therapy of likelihood of nasal irritation; may become less bothersome with continued use.e

  • Advise patients receiving oral inhalation of likelihood of mild irritation of the mouth or throat and cough; may become tolerant of these effects.g

  • Importance of patients taking lozenges to stop use and contact clinician if mouth problems, persistent indigestion, severe sore throat, irregular heartbeat or palpitations occur.h Patients receiving nicotine polacrilex gum should stop use and contact clinician if mouth, teeth, or jaw problems, or irregular heartbeat or palpitations occur.c

  • Importance of informing patients with phenylketonuria that Commit nicotine polacrilex lozenges contain aspartame.h

  • Importance of consulting clinician if patient feels the need for continued therapy at the end of regimen.190 264 a b i

  • Risk of dependence to nicotine in oral inhaler and nasal spray; importance of using inhaler and nasal spray only as long as directed by clinician.d g

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.d g

  • Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., chronic nasal problems, heart problems, high BP, stomach ulcers, wheezing or asthma, overactive thyroid, diabetes requiring insulin, kidney or liver disease).d

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

* 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*

Nicotine Transdermal System

7 mg/24 hours (36 mg/7 cm2)

Nicoderm CQ Clear Step 3

GlaxoSmithKline

NicoDerm CQ Step 3

GlaxoSmithKline

11 mg/24 hours

Nicotine Transdermal System

14 mg/24 hours*

Nicotine Transdermal System

14 mg/24 hours (78 mg/15 cm2)

Nicoderm CQ Clear Step 3

GlaxoSmithKline

NicoDerm CQ Step 2

GlaxoSmithKline

21 mg/24 hours*

Nicotine Transdermal System

21 mg/24 hours (114 mg/22 cm2)

NicoDerm CQ Step 1

GlaxoSmithKline

* 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

4 mg (of nicotine)

Commit

GlaxoSmithKline

Pieces, chewing gum

2 mg (of nicotine)*

Nicorette

GlaxoSmithKline

Nicotine Polacrilex Gum

4 mg (of nicotine)*

Nicorette DS

GlaxoSmithKline

Nicotine Polacrilex Gum

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Nicotine 21MG/24HR Patches (WATSON LABS): 30/$168.99 or 90/$479.93

Nicotrol 10MG Inhaler (PFIZER U.S.): 168/$212.94 or 504/$604.54

Nicotrol NS 10MG/ML Solution (PFIZER U.S.): 40/$207.10 or 120/$595.12

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions February 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† 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].

3. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:1732.

4. Taylor P. Agents acting at the neuromuscular junction and autonomic ganglia. In: Gilman AG, Rall TW, Nies AS et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press; 1990:166-86.

5. Russell MAH, Raw M, Jarvis MJ. Clinical use of nicotine chewing-gum. Br Med J. 1980; 280:1599-602. [IDIS 116400] [PubMed 7000247]

6. Raw M, Jarvis MJ, Feyerabend C et al. Comparison of nicotine chewing-gum and psychological treatments for dependent smokers. Br Med J. 1980; 281:481-2. [IDIS 119173] [PubMed 7427329]

7. Jarvis MJ, Raw M, Russell MAH et al. Randomized controlled trial of nicotine chewing-gum. BMJ. 1982; 285:537-40. [IDIS 155810] [PubMed 6809161]

8. Fagerstrom K-O. A comparison of psychological and pharmacological treatment in smoking cessation. J Behav Med. 1982; 5:343-51. [PubMed 7131548]

9. Schneider NG, Jarvik ME, Forsythe AB et al. Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial. Addict Behav. 1983; 8:253-61. [PubMed 6666689]

10. Wilhelmsen L, Hjalmarsson A. Smoking cessation experience in Sweden. Can Fam Physician. 1980; 26:737-43. [PubMed 21293578]

11. Russell MAH, Merriman R, Stapleton J et al. Effect of nicotine chewing gum as an adjunct to general practitioners’ advice against smoking. BMJ. 1983; 287:1782-5. [IDIS 179862] [PubMed 6416593]

12. Russell MAH, Feyerabend C. Cigarette smoking: a dependence on high-nicotine boli. Drug Metab Rev. 1978; 8:29-57. [PubMed 31270]

13. Kalter H, Warkany J. Congenital malformations (second of two parts). N Engl J Med. 1983; 308:491-7 (IDIS 165815) [IDIS 165815] [PubMed 6337336]

14. Johnston C. Cigarette smoking and the outcome of human pregnancies: a status report on the consequences. Clin Toxicol. 1981; 18:189-209. [IDIS 134357] [PubMed 7226732]

15. Landesman-Dwyer S, Emanuel I. Smoking during pregnancy. Teratology. 1979; 19:119-26. [PubMed 377552]

16. Abel EL. Smoking during pregnancy: a review of effects on growth and development of offspring. Hum Biol. 1980; 52:593-625. [PubMed 7009384]

17. Gennser G, Marsal K, Brantmark B. Maternal smoking and fetal breathing movements. Am J Obstet Gynecol. 1975; 123:861-7. [PubMed 1106202]

18. Dougherty CRS, Jones AD. The determinants of birth weight. Am J Obstet Gynecol. 1982; 144:190-200. [IDIS 146870] [PubMed 7114129]

19. Chernick V, Childiaeva R, Ioffe S. Effects of maternal alcohol intake and smoking on neonatal electroencephalogram and anthropometric measurements. Am J Obstet Gynecol. 1983; 146:41-7. [IDIS 170179] [PubMed 6846423]

20. Meyer MB. How does maternal smoking affect birth weight and maternal weight gain?: evidence from the Ontario perinatal mortality study. Am J Obstet Gynecol. 1978; 131:888-93. [IDIS 115309] [PubMed 686089]

21. Lehtovirta P, Dorss M. The acute effect of smoking on intervillous blood flow of the placenta. Br J Obstet Gynaecol. 1978; 85:729-31. [PubMed 708655]

22. Persson PH, Grennert L, Gennser G et al. A study of smoking and pregnancy with special reference to fetal growth. Acta Obstet Gynecol Scand. 1978; 78(Suppl):33-9.

23. Butler NR, Goldstein H, Ross EM. Cigarette smoking in pregnancy: its influence on birth weight and perinatal mortality. Br Med J. 1972; 2:127-30. [PubMed 5017304]

24. Davies DP, Gray OP, Ellwood PC et al. Cigarette smoking in pregnancy: association with maternal weight gain and fetal growth. Lancet. 1976; 1:385-7. [PubMed 55649]

25. Ferno O, Lichtneckert SJA, Lundgren CEG. A substitute for tobacco smoking. Psychopharmacologia. 1973; 31:201-4. [PubMed 4732726]

26. Ashton H. Teratogenic drugs. Adverse Drug React Bull. 1983; (101):372-5.

27. McNabb ME, Ebert RV, McCusker K. Plasma nicotine levels produced by chewing nicotine gum. JAMA. 1982; 248:865-8. [IDIS 154514] [PubMed 7047783]

28. Feyerabend C, Russell MAH. Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum. Br J Clin Pharmacol. 1978; 5:293-7.

29. Russell MAH, Wilson C, Feyerabend C et al. Effect of nicotine chewing-gum on smoking behaviour and as an aid to cigarette withdrawal. Br Med J. 1976; 2:391-3. [IDIS 63651] [PubMed 779926]

30. Brantmark B, Ohlin O, Westling H. Nicotine containing chewing gum as an anti-smoking aid. Psychopharmacologia. 1973; 31:191-200. [IDIS 39703] [PubMed 4581737]

31. Puska P, Bjorkqvist S, Koskela K. Nicotine-containing chewing gum in smoking cessation: a double blind trial with half-year follow-up. Addict Behav. 1979; 4:141-6. [PubMed 382765]

32. Stalhandske T. Effects of increased liver metabolism of nicotine on its uptake, elimination, and toxicity in mice. Acta Physiol Scand. 1970; 80:222-34. [PubMed 5475342]

33. Glantz LA. Nicotine chewing gum not for all smokers. Clin Pharm. 1984; 3:236. [IDIS 185520] [PubMed 6734086]

34. US Department of Health, Education, and Welfare. US Surgeon General’s report on smoking and health. DHEW Publ. No. [PHS] 79-50066. Washington, DC: US Government Printing Office; 1979:1-1164.

35. Koop CE, Luoto J. “The health consequences of smoking: cancer,” overview of a report of the Surgeon General. Public Health Rep. 1982; 97:318-24. [PubMed 7111654]

36. Gosselin RE, Hodge HC, Smith RP et al. Clinical toxicology of commercial products: acute poisoning. 5th ed. Baltimore: Williams & Wilkins Co; 1984:II237, III311-4.

37. Nicotine. From: TDB, Toxicology Data Bank (database). Bethesda, MD: National Library of Medicine, 1984; TDB No 1107.

38. Issac PF, Rand MJ. Cigarette smoking and plasma levels of nicotine. Nature. 1972; 236:308-10. [PubMed 4552162]

39. Rosenberg J, Benowitz NL, Jacob P et al. Disposition kinetics and effects of intravenous nicotine. Clin Pharmacol Ther. 1980; 28:517-22. [IDIS 125483] [PubMed 7408411]

40. Benowitz NL, Kuyt F, Jacob P et al. Cotinine disposition and effects. Clin Pharmacol Ther. 1983; 34:604-11. [IDIS 178351] [PubMed 6627820]

41. Langone JJ, Gjika HB, Van Vunakis H. Nicotine and its metabolites: radioimmunoassays for nicotine and cotinine. Biochemistry. 1973; 12:5025-30. [PubMed 4761980]

42. Evans D, Lane DS. Long-term outcome of smoking cessation workshops. Am J Public Health. 1980; 70:725-7. [PubMed 7386710]

43. Reviewers’ comments (personal observations).

44. Marion Merrell Dow, Kansas City, MO: Personal communication.

45. Benowitz NL. The use of biologic fluid samples in assessing tobacco smoke consumption. In: Grabowski J, Bell CS, eds. Measurement in the analysis and treatment of smoking behavior. NIDA Research Monograph 48. DHHS Pub No. [ADM] 83-1285. Washington, DC: US Government Printing Office; 1983:6-26.

46. Malcolm RE, Sillett RW, Turner JAM et al. The use of nicotine gum as an aid to stopping smoking. Psychopharmacology. 1980; 70:295-6. [PubMed 6777804]

47. Fee WM, Stewart MJ. A controlled trial of nicotine chewing gum in a smoking withdrawal clinic. Practitioner. 1982; 226:148-51. [IDIS 146084] [PubMed 7043437]

48. British Thoracic Society. Comparison of four methods of smoking withdrawal in patients with smoking related diseases. BMJ. 1983; 286:595-7. [PubMed 6402162]

49. Anon. Nicotine gum. Med Lett Drugs Ther. 1984; 26:47-8. [PubMed 6717371]

50. Henningfield JE. Behavioral pharmacology of cigarette smoking. Adv Behav Pharmacol. (in press).

51. Henningfield JE, Miyasato K, Jasinski DR. Cigarette smokers self-administer intravenous nicotine. Pharmacol Biochem Behav. 1983; 19:887-90. [PubMed 6647522]

52. Henningfield JE, Goldberg SR. Nicotine as a reinforcer in human subjects and laboratory animals. Pharmacol Biochem Behav. 1983; 19:989-92. [PubMed 6657732]

53. Dawson GW, Vestal RE. Smoking and drug metabolism. Pharmacol Ther. 1982; 15:207-21.

54. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1980:159-60, 176-8.

55. Merrell Dow Pharmaceuticals Inc. Data on file. Cincinnati, OH.

56. Food and Drug Administration. Smoking deterrent drug products for over-the-counter human use; establishment of a monograph. [Docket No. 81N-0027] Fed Regist. 1982; 47:490-500.

57. Jusko WJ. Role of tobacco smoking in pharmacokinetics. J Pharmacokinet Biopharm. 1978; 6:7-39. [PubMed 349132]

58. Fuhrmann C (personal observations); 1984 Jun 7.

59. Falkeborn Y, Larsson C, Nordberg A. Chronic nicotine exposure in rat: a behavioural and biochemical study of tolerance. Drug Alcohol Depend. 1981; 8:51-60. [PubMed 7297412]

60. Tsujimoto A, Nakashima T, Tanino S et al. Tissue distribution of [3H]nicotine in dogs and rhesus monkeys. Toxicol Appl Pharmacol. 1975; 32:21-31. [PubMed 1135877]

61. Griffiths MC (The United States Pharmacopeial Convention, Inc., Rockville, MD): Personal communication; 1984 Jun 29.

62. The United States pharmacopeia, 21st rev, and The national formulary, 16th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1984:1587-9.

63. Benowitz NL, Jacob P III, Jones RT et al. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther. 1980; 221:368-72.

64. Russell MAH, Wilson C, Taylor C et al. Effect of general practitioners’ advice against smoking. Br Med J. 1979; 2:231-5. [PubMed 476401]

65. Hall SM, Tunstall C, Rugg D et al. Nicotine gum and behavioral treatment in smoking cessation. J Consult Clin Psychol. (in press)

66. Vocci FJ Jr (US Public Health Service, Rockville, MD): Personal communication; 1984 Jun 29.

67. Blum A. Nicotine chewing gum and the medicalization of smoking. Ann Intern Med. 1984; 101:121-3. [IDIS 188171] [PubMed 6375499]

68. Christen AG, McDonald JL, Olson BL. Efficacy of nicotine chewing gum in facilitating smoking cessation. J Am Dent Assoc. 1984; 108:594-7. [PubMed 6373886]

69. Anon. Smoking and cancer. MMWR Morb Mortal Wkly Rep. 1982; 31:77-80. [PubMed 6801462]

70. Luck W, Nau H. Exposure of the fetus, neonate, and nursed infant to nicotine and cotinine from maternal smoking. N Engl J Med. 1984; 311:672. [IDIS 189581] [PubMed 6472348]

71. Lees AJ. Hemidystonia relieved by nicotine. Lancet. 1984; 2:871. [IDIS 191364] [PubMed 6148600]

72. Anon. Dental effects of nicotine gum. Med Lett Drugs Ther. 1984; 26:98. [PubMed 6384754]

73. Luck W, Nau H. Nicotine and cotinine concentrations in serum and urine of infants exposed via passive smoking or milk from smoking mothers. J Pediatr. 1985; 107:816-20. [IDIS 209627] [PubMed 4056988]

74. Fielding JE. Smoking: health effects and control. (Second of two parts.) N Engl J Med. 1985; 313:555-61.

75. Eraker SA, Becker MH, Strecher VJ et al. Smoking behavior, cessation techniques, and the health decision model. Am J Med. 1985; 78:817-25. [PubMed 3887912]

76. Raw M. Does nicotine chewing gum work? Br Med J. 1985; 290:1231-2.

77. Anon. Nicotine chewing gum. Lancet. 1985; 1:320-1. [PubMed 2857369]

78. Hughes JR, Hatsukami DK, Pickens RW et al. Effect of nicotine on the tobacco withdrawal syndrome. Psychopharmacology (Berl). 1984; 83:82-7. [PubMed 6429705]

79. West RJ, Jarvis MJ, Russell MAH et al. Effect of nicotine replacement on the cigarette withdrawal syndrome. Br J Addict. 1984; 79:215-9. [IDIS 188421] [PubMed 6589006]

80. Schneider NG, Jarvik ME, Forsythe AB. Nicotine vs. placebo gum in the alleviation of withdrawal during smoking cessation. Addict Behav. 1984; 9:149-56. [PubMed 6741676]

81. Shapiro J. Nicotine chewing gum in general practice. BMJ. 1984; 289:1308. [IDIS 192764] [PubMed 6437528]

82. Clavel F, Benhamou S. Désintoxication tabagique. Comparaison de l’efficacité de différentes méthodes. Résultats intermédiaires d’une étude comparative. (French; with English abstract.) Presse Med. 1984; 13:975-7.

83. Clavel F, Benhamou S. Nicotine chewing gum in general practice. BMJ. 1984; 289:1308. [IDIS 192764] [PubMed 6437528]

84. Marshall A, Raw M. Nicotine chewing gum in general practice: effect of follow up appointments. BMJ. 1985; 290:1397-8. [PubMed 3922510]

85. Jamrozik K, Fowler G, Vessey M et al. Placebo controlled trial of nicotine chewing gum in general practice. BMJ. 1984; 289:794-7. [IDIS 191528] [PubMed 6434084]

86. American College of Physicians Health and Public Policy Committee. Methods for stopping cigarette smoking. Ann Intern Med. 1986; 105:281-91. [IDIS 219663] [PubMed 3729208]

87. Hughes JR, Hatsukami DK, Skoog KP. Physical dependence on nicotine in gum: a placebo substitution trial. JAMA. 1986; 255:3277-9. [IDIS 216949] [PubMed 3712681]

88. West RJ, Russell MAH. Effects of withdrawal from long-term nicotine gum use. Psychol Med. 1985; 15:891-3. [PubMed 4080892]

89. Hjalmarson AIM. Effect of nicotine chewing gum in smoking cessation: a randomized, placebo-controlled, double-blind study. JAMA. 1984; 252:2835-8. [IDIS 192341] [PubMed 6387207]

90. Hughes JR, Miller SA. Nicotine gum to help stop smoking. JAMA. 1984; 252:2855-8. [IDIS 192342] [PubMed 6387208]

91. McNabb ME, McClellan JL. Nicotine gum addiction? JAMA. 1984; 252:2890. Letter.

92. Goodman RP, Douglas CR. Rash from nicotine gum. South Med J. 1987; 80:539. [IDIS 228245] [PubMed 3563596]

93. Lee BL, Benowitz NL, Jacob P III. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med. 1987; 106:553-5. [IDIS 227979] [PubMed 3826954]

94. Benowitz NL, Jacob P III, Savanapridi C. Determinants of nicotine intake while chewing nicotine polacrilex gum. Clin Pharmacol Ther. 1987; 41:467-73. [IDIS 229516] [PubMed 3829583]

95. Krivokapich J, Schneider NG, Child JS et al. Cardiovascular effects of nicotine gum and cigarettes assessed by ECG and echocardiography. In: Grabowski J, Hall SM, eds. Pharmacological adjuncts in smoking cessation. NIDA Research Monograph 53. DHHS Pub No. [ADM] 85-1333. Washington, DC: US Government Printing Office; 1985:42-55.

96. Tonnesen P, Fryd V, Hansen M et al. Effect of nicotine chewing gum in combination with group counseling on the cessation of smoking. N Engl J Med. 1988; 318:15-8. [IDIS 236483] [PubMed 3336380]

97. US Department of Health and Human Services. The health consequences of smoking: nicotine addiction. A report of the Surgeon General. Washington, DC: US Government Printing Office; 1988.

98. Hajek P, Jackson P, Belcher M. Long-term use of nicotine chewing gum: occurrence, determinants, and effect on weight gain. JAMA. 1988; 260:1593-6. [IDIS 245658] [PubMed 3411739]

99. Anon. The Surgeon General’s 1990 report on the health benefits of smoking cessation: executive summary. MMWR Morb Mortal Wkly Rep. 1990; 39:1-12. [PubMed 2294395]

100. Henningfield JE, Radzius A, Cooper TM et al. Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum. JAMA. 1990; 264:1560-4. [IDIS 271862] [PubMed 2395197]

101. Basel Pharmaceuticals. Habitrol (nicotine transdermal therapeutic system) prescribing information. Summit, NJ; 1991 Nov.

102. Marion Merrell Dow. Nicoderm (nicotine transdermal system) prescribing information. Kansas City, MO; 1991 Nov.

103. Lederle Laboratories Division. Prostep (nicotine transdermal system) prescribing information. Pearl River, NY; 1992 Jun.

104. Parke-Davis. Nicotrol (nicotine transdermal system) prescribing information. Morris Plains, NJ; 1992 March 5.

105. Dubois JP, Sioufi A, Müller P et al. Pharmacokinetics and bioavailability of nicotine in healthy volunteers following single and repeated administration of different doses of transdermal nicotine systems. Methods Find Exp Clin Pharmacol. 1989; 11:187-95. [PubMed 2725117]

106. Ross HD, Chan KKH, Piraino AJ et al. Pharmacokinetics of multiple daily transdermal doses of nicotine in healthy smokers. Pharmaceut Res. 1991; 8:385-8.

107. Caspary S, Keller-Stanislawski B, Huber T et al. Pharmacokinetics of nicotine after application of a 30 cm2 nicotine patch under steady-state conditions. Int J Clin Pharmacol Ther Toxicol. 1991; 29:92-5. [PubMed 2071260]

108. Bannon YB, Corish J, Corrigan OI et al. Transdermal delivery of nicotine in normal human volunteers: a single dose and multiple dose study. Eur J Clin Pharmacol. 1989; 37:285-90. [IDIS 260029] [PubMed 2612544]

109. Mulligan SC, Masterson JG, Devane JG et al. Clinical and pharmacokinetic properties of a transdermal nicotine patch. Clin Pharmacol Ther. 1990; 47:331-7. [IDIS 264323] [PubMed 2311334]

110. Gorsline J, Benowitz NL, Rolf CN et al. Comparison of plasma nicotine concentrations for nicotine transdermal system (NTS), cigarette smoking and nicotine polacrilex (nicotine gum). Clin Pharmacol Ther. 1992; 51:129.

111. Daughton DM, Heatlye SA, Prendergast JJ et al. Effect of transdermal nicotine delivery as an adjunct to low-intervention smoking cessation therapy. Arch Intern Med. 1991; 151:749-52. [IDIS 280489] [PubMed 2012458]

112. Rose JE, Levin ED, Behm FM et al. Transdermal nicotine facilitates smoking cessation. Clin Pharmacol Ther. 1990; 47:323-30. [IDIS 264322] [PubMed 2178852]

113. Abelin T, Buehler A, Müller P et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet. 1989; 1:7-9. [IDIS 249933] [PubMed 2563045]

114. Abelin T, Ehrsam R, Bühler-Reicher et al. Effectiveness of a transdermal nicotine system in smoking cessation studies. Methods Find Exp Clin Pharmacol. 1989; 11:205-14. [PubMed 2657276]

115. Hurt RD, Lauger GG, Offord KP et al. Nicotine-replacement therapy with use of a transdermal nicotine patch—a randomized double-blind placebo-controlled trial. Mayo Clin Proc. 1990; 65:1529-37. [IDIS 287497] [PubMed 2255215]

116. Peter JA. Nicotine-replacement therapy in cessation of smoking. Mayo Clin Proc. 1990; 65:1619-23. [IDIS 287501] [PubMed 2255223]

117. Russell MAH. The future of nicotine replacement. Br J Addict. 1991; 86:653-8. [IDIS 284065] [PubMed 1859935]

118. Tonnesen P, Norregaard J, Simonsen K et al. A double-blind trial of a 16-hour transdermal nicotine patch in smoking cessation. N Engl J Med. 1991; 325:311-5. [IDIS 283295] [PubMed 2057036]

119. Morgan GD, Villagra VG. The nicotine transdermal patch: a cautionary note. Ann Intern Med. 1992; 116:424. [IDIS 291814] [PubMed 1736778]

120. Benowitz NL, Chan K, Denaro CP et al. Stable isotope method for studying transdermal drug absorption: the nicotine patch. Clin Pharmacol Ther. 1991; 50:286-93. [IDIS 289390] [PubMed 1914363]

121. Müller P, Abelin T, Ehrsam R et al. The use of transdermal nicotine in smoking cessation. Lung. 1990; Suppl:445-53.

122. Lederle Laboratories. Prostep product information. Pearl River, NY; 1992 Jan.

123. Benowitz NL. Pharmacodynamics of nicotine: implications for rational treatment of nicotine addiction. Br J Addict. 1991; 495-9.

124. Rose JE, Herskovic JE, Trilling Y et al. Transdermal nicotine reduces cigarette craving and nicotine preference. Clin Pharmacol Ther. 1985; 38:450-6. [IDIS 206896] [PubMed 4042528]

125. Srivastave ED, Russell MAH, Feyerabend C et al. Transdermal nicotine in active ulcerative colitis. Clin Exp Pharmacol. 1991; 78.2:57.

126. Buchkremer G, Minneker E, Block M. Smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy. Pharmacopsychiatry. 1991; 24: 96-102. [PubMed 1891488]

127. Ranade VV. Drug delivery systems, 6, transdermal drug delivery. J Clin Pharmacol. 1991; 31:401-18. [IDIS 282247] [PubMed 2050824]

128. Benowitz NL. Nicotine replacement therapy during pregnancy. JAMA. 1991; 266:3174-7. [IDIS 288934] [PubMed 1956108]

129. Marion Merrell Dow. Nicoderm (nicotine transdermal system) patient instructions. Kansas City, MO; 1991 Nov.

130. Anon. Skin patches to prevent lung cancer. Eur J Cancer. 1991; 27:223-4. [PubMed 1827299]

131. Varma JR. Transdermal nicotine patch for smoking cessation. N Engl J Med. 1992; 326:344. [PubMed 1728742]

132. Tonnesen P, Norregaard J, Simonsen K et al. Transdermal nicotine patch for smoking cessation. N Engl J Med. 1992; 326:345.

133. Hughes JR, The Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. Am Rev Respir Dis. 1992; 145:A685.

134. Glover ED. Transdermal nicotine for smoking cessation. N Engl J Med. 1992; 326:344. [IDIS 290611] [PubMed 1728741]

135. Hartman N, Leong GB, Glynn SM et al. Transdermal nicotine and smoking behavior in psychiatric patients. Am J Psychiatry. 1991; 148:374-5. [IDIS 278593] [PubMed 1992843]

136. Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation: six-month results from two multicenter controlled clinical trials. JAMA. 1991; 266:3133-8. [IDIS 288933] [PubMed 1956099]

137. Anon. Nicotine patches. Med Lett Drugs Ther. 1992; 34:37-8. [PubMed 1556994]

138. Lederle Laboratories. The Prostep patch and support services: important aids to a comprehensive stop-smoking program. Pearl River, NY; 1992 Feb.

139. Seidman DS, Stevenson DK. Nicotine replacement therapy during pregnancy. JAMA. 1992; 267:1922. [IDIS 294313] [PubMed 1548823]

140. Benowitz NL. Nicotine replacement therapy during pregnancy. JAMA. 1992; 267:1922. [IDIS 294313] [PubMed 1548823]

141. Minneker-Hügel E, Unland H, Buchkremer G. Behavioral relapse prevention strategies in smoking cessation. Int J Addict. 1992; 27:627-34. [PubMed 1601540]

142. Gorsline J, Okerholm RA, Rolf CN et al. Comparison of plasma nicotine concentrations after application of nicoderm (nicotine transdermal system) to different skin sites. J Clin Pharmacol. 1992; 32:576-81. [IDIS 298489] [PubMed 1634647]

143. Bronson DL. Transdermal nicotine system for smoking cessation. Therapeutics. 1992 May/June:80.

144. Palmer KJ, Buckley MM, Faulds D. Transdermal nicotine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy as an aid to smoking cessation. Drugs. 1992; 44:498-529. [PubMed 1382940]

145. Benowitz NL, Jacob P III, Olsson P et al. Intravenous nicotine retards transdermal absorption of nicotine: evidence of blood flow—limited percutaneous absorption. Clin Pharmacol Ther. 1992; 52:223-30. [IDIS 302452] [PubMed 1526077]

146. Kochak GM, Sun JX, Choi RL et al. Pharmacokinetic disposition of multiple-dose transdermal nicotine in healthy adult smokers. Pharm Res. 1992; 9:1451-5. [PubMed 1475232]

147. Schneider NG. Nicotine therapy in smoking cessation. Pharmacokinetic considerations. Clin Pharmacokinet. 1992; 23:169-72. [PubMed 1511534]

148. Benowitz NL. Nicotine replacement therapy. What has been accomplished—can we do better? Drugs. 1993; 45: 157-170.

149. Fiore MC, Jorenby DE, Baker TB et al. Tobacco dependence and the nicotine patch. Clinical guidelines for effective use. JAMA. 1992; 268:2687-94. [IDIS 305330] [PubMed 1304736]

150. Gupta SK, Okerholm RA, Coen P et al. Single- and multiple-dose pharmacokinetics of Nicoderm (nicotine transdermal system). J Clin Pharmacol. 1993; 33:169-74. [IDIS 312972] [PubMed 8440767]

151. Gorsline J, Gupta SK, Dye D et al. Steady-state pharmacokinetics and dose relationship of nicotine delivered from Nicoderm (nicotine transdermal system). J Clin Pharmacol. 1993; 33:161-8. [IDIS 312971] [PubMed 8440766]

152. Sutherland G, Russell MA, Stapleton J et al. Nasal nicotine spray: a rapid nicotine delivery system. Psychopharmacology (Berl). 1992; 108:512-8. [PubMed 1410168]

153. Pomerleau OF, Flessland KA, Pomerleau CS et al. Controlled dosing of nicotine via an Intranasal Nicotine Aerosol Delivery Device (INADD). Psychopharmacology (Berl). 1992; 108:519-26. [PubMed 1410169]

154. Johansson CJ, Olsson P, Bende M et al. Absolute bioavailability of nicotine applied to different nasal regions. Eur J Clin Pharmacol. 1991; 41:585-8. [IDIS 292547] [PubMed 1815971]

155. Lee EW, D’Alonzo GE. Cigarette smoking, nicotine addiction, and its pharmacologic treatment. Arch Intern Med. 1993; 153:34-48. [IDIS 308303] [PubMed 8422199]

156. Rennard S, Daughton D, Fortmann S et al. Transdermal nicotine enhances smoking cessation in coronary artery disease patients. Chest. 1991; 100:5S.

157. Mueller P, Abelin T, Ehrsam R et al. The use of transdermal nicotine in smoking cessation. Lung. 1990; 168(Suppl):445-53. [PubMed 2117147]

158. Foulds J, Stapleton J, Feyerabend C et al. Effect of transdermal nicotine patches on cigarette smoking: a double blind crossover study. Psychopharmacology (Berl). 1992; 106:421-7. [PubMed 1570391]

159. Minneker E, Buchkremer G, Block M. The effect of different dosages of a transdermal nicotine substitution system on the success rate of smoking cessation therapy. Methods Find Exp Clin Pharmacol. 1989; 11:219-22. [PubMed 2725119]

160. Norregaard J, Tonnesen P, Simonsen K et al. Long-term nicotine substitution after application of a 16-hour nicotine patch in smoking cessation. Eur J Clin Pharm.

161. Eichelberg D, Stolze P, Block M et al. Contact allergies induced by TTS-treatment. Methods Find Exp Clin Pharmacol. 1989; 11:223-5. [PubMed 2725120]

162. Tonnesen P, Norregaard J, Sawe U et al. Recycling with nicotine patches in smoking cessation. Addiction. 1993; 88:533-9. [IDIS 313540] [PubMed 8485431]

163. Bircher AJ, Howald H, Rufli T. Adverse skin reactions to nicotine in a transdermal therapeutic system. Contact Dermatitis. 1991; 25:230-6. [PubMed 1839264]

164. Hwang SL, Waldholt M. Heart attacks reported in patch users still smoking. The Wall Street Journal: B1, June 19, 1992.

165. Ottervanger JP, Stricker BHC, Klomps HC. Transdermal nicotine: clarifications, side effects, and funding. JAMA. 1993; 269:1940. [IDIS 312645] [PubMed 8464119]

166. Fagerström KO, Schneider NG, Lunnel E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology. (in press)

167. Lederle Laboratories, Pearl River, NY: Personal communication.

168. Hilleman DE, Mohiuddin SM, Delcore MG. Comparison of fixed-dose transdermal nicotine, tapered-dose transdermal nicotine and buspirone in smoking cessation. J Allergy Clin Immunol. 1993:171. Abstract.

169. Grenhoff J, Svensson TH. Pharmacology of nicotine. Br J Addict. 1989; 84:477-92. [PubMed 2568138]

170. Abood LG, Banerjee S, Kanne DB. Sites, mechanisms, and structural characteristics of the brain’s nicotine receptor. J Subst Abuse. 1989; 1:259-71. [PubMed 7580218]

171. Gora ML. Nicotine transdermal systems. Ann Pharmacother. 1993; 27:742-50. [IDIS 316103] [PubMed 8329798]

172. Benowitz NL. Pharmacologic aspects of cigarette smoking and nicotine addiction. N Engl J Med. 1988; 319: 1318-30.

173. Balfour DJ. The influence of stress on psychopharmacological responses to nicotine. Br J Addict. 1991; 86:489-93. [PubMed 1859910]

174. Corrigall WA. Understanding brain mechanisms in nicotine reinforcement. Br J Addict. 1991; 86:507-10. [IDIS 284050] [PubMed 1859913]

175. Stolerman IP. Behavioural pharmacology of nicotine: multiple mechanisms. Br J Addict. 1991; 86:533-6. [IDIS 284055] [PubMed 1650269]

176. Prather RD, Tu TG, Rolf CN et al. Nicotine pharmacokinetics of Nicoderm (nicotine transdermal system) in women and obese men compared with normal-sized men. J Clin Pharmacol. 1993; 33:644-9. [IDIS 318361] [PubMed 8366189]

177. Paoletti P, Tonnesen P, Rodriquez-Roisin R. CEASE (Collaborative European Anti-Smoking Evaluation). A challenging multicenter trial organized by the European Respiratory Society. Chest. 1993; 103:1317-9. [PubMed 8486002]

188. McNeil Consumer Products Company. Nicotrol (nicotine) transdermal system patient information & instructions. Fort Washington, PA. Undated.

189. SmithKline Beecham Consumer Healthcare. NicoDermCQ patient information. Philadelphia, PA. Undated.

190. SmithKline Beecham Consumer Healthcare. Nicorette (nicotine polacrilex) gum patient information (dated 1997). In: Physicians’ desk reference for nonprescription drugs. 20th ed. Montvale, NJ: Medical Economics Company Inc; 1999:780-2.

191. McNeil Consumer Products Co. NicotrolNS (nicotine) nasal spray prescribing information. Fort Washington, PA; 1996 March 21.

192. Fiscella K, Franks P. Cost-effectiveness of the transdermal nicotine patch as an adjunct to physicians’ smoking cessation counseling. JAMA. 1996; 275:1247-51. [IDIS 363516] [PubMed 8601956]

193. Fiore MC, Smith SS, Jorenby DE et al. The effectiveness of the nicotine patch for smoking cessation: a meta-analysis. JAMA. 1994; 271:1940-7. [IDIS 331519] [PubMed 8201739]

194. The Smoking Cessation Clinical Practice Guideline Panel and Staff. The Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline. JAMA. 1996; 275:1270-80. [IDIS 363517] [PubMed 8601960]

195. Fiore MC, Bailey WC, Cohen SJ et al. Smoking cessation: clinical practice guideline. No. 18. Rockville, MD: US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research. AHCPR publication No. 96-0692.

196. American Psychiatric Association Work Group on Nicotine Dependence. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry. 1996; 153(Suppl Oct):1-31.

197. Hughes JR. Treatment of nicotine Dependence: is more better? JAMA. 1995; 274:1390-1. Editorial. (IDIS 355388)

198. Sachs DPL. Effectiveness of the 4-mg dose of nicotine polacrilex for the initial treatment of high-dependent smokers. Arch Intern Med. 1995; 155:1973-80. [IDIS 355153] [PubMed 7575051]

199. Gourlay SG, Forbes A, Marriner T et al. Double blind trial of repeated treatment with transdermal nicotine for relapsed smokers. BMJ. 1995; 311:363-6. [IDIS 351826] [PubMed 7640544]

200. Working Group for the Study of Transdermal Nicotine in Patients with Coronary Artery Disease. Nicotine replacement therapy for patients with coronary artery disease. Arch Intern Med. 1994; 154:989-95. [IDIS 329351] [PubMed 8179456]

201. Sutherland G, Stapleton JA, Russell MAH et al. Randomised controlled trial of nasal nicotine spray in smoking cessation. Lancet. 1992; 340:324-9. [IDIS 300522] [PubMed 1353803]

202. Hjalmarson A, Franzon M, Westin A et al. Effect of nicotine nasal spray on smoking cessation. Arch Intern Med. 1994; 154:2567-72. [IDIS 339425] [PubMed 7979853]

203. Schneider NG, Olmstead R, Mody FV et al. Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial. Addiction. 1995; 90:1671-82. [PubMed 8555958]

204. Sandborn WJ, Tremaine WJ, Offord KP et al. Transdermal nicotine for mildly to moderately active ulcerative colitis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997; 126:364-71. [IDIS 380435] [PubMed 9054280]

205. Bonapace CR, Mays DA. The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease. Ann Pharmacother. 1997; 31:907-12. [IDIS 389360] [PubMed 9220055]

206. Pullan RD, Rhodes J, Ganesh S et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994; 330:811-5. [IDIS 326793] [PubMed 8114833]

207. Hanauer SB. Nicotine for colitis—the smoke has not yet cleared. N Engl J Med. 1994; 330:856-7. [IDIS 326795] [PubMed 8114839]

208. Kennedy LD. Nicotine therapy for ulcerative colitis. Ann Pharmacother. 1996; 30:1022-3. [IDIS 372137] [PubMed 8876866]

209. Rhodes J, Thomas G. Nicotine treatment in ulcerative colitis: current status. Drugs. 1995; 49:157-60. [PubMed 7729324]

210. Thomas GAO, Rhodes J, Mani V et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med. 1995; 332:988-92. [IDIS 345129] [PubMed 7885427]

211. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. 1997; 29:1422-31. [IDIS 385817] [PubMed 9180099]

212. Ottervanger JP, Festen JM, de Vries AG et al. Acute myocardial infarction while using the nicotine patch. Chest. 1995; 107:1765-6. [IDIS 349182] [PubMed 7781384]

213. Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994; 120:695. [IDIS 327661] [PubMed 8135462]

214. Jackson M. Cerebral arterial narrowing with nicotine patch. Lancet. 1993; 342:236-7. [IDIS 318298] [PubMed 8100951]

215. Pierce JR Jr. Stroke following application of a nicotine patch. Ann Pharmacother. 1994; 28:402. [IDIS 327491] [PubMed 8193434]

216. Kafka HP. Heart attacks, smoking, and the nicotine patch. Ann intern Med. 1994; 121:389. [IDIS 334422] [PubMed 8042844]

217. Mittleman MA. Smoking while wearing a nicotine patch. Ann Intern Med. 1995; 122:476-7. [IDIS 343620] [PubMed 7857004]

218. Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994; 120:695. [IDIS 327661] [PubMed 8135462]

219. Lagrue G, Verra F, Lebargy F. Nicotine patches and vascular risks. Lancet. 1993; 342:564. [IDIS 319897] [PubMed 8102710]

220. Jackson M. Nicotine patches and vascular risks. Lancet. 1993; 342:564. [IDIS 319897] [PubMed 8102710]

221. Joseph AM, Norman SM, Ferry LH et al. The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. N Engl J Med. 1996; 335:1792-8. [IDIS 378769] [PubMed 8943160]

222. Mahmarian JJ, Moye LA, Nasser GA et al. Nicotine patch therapy in smoking cessation reduces the extent of exercise-induced myocardial ischemia. J Am Coll Cardiol. 1997; 30:125-30. [IDIS 389307] [PubMed 9207632]

223. Kottke TE. Managing nicotine dependence. J Am Coll Cardiol. 1997; 30:131-2. [IDIS 389308] [PubMed 9207633]

224. Rigotti NA, Eagle KA. Atrial fibrillation while chewing nicotine gum. JAMA. 1986; 255:1018. [IDIS 210971] [PubMed 3945010]

225. Murray RP, Bailey WC, Daniels K et al. Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Chest. 1996; 109:438-45. [IDIS 363928] [PubMed 8620719]

226. Keeley EC, Pirwitz MJ, Landau C et al. Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions. Am J Med. 1996; 171:357-63.

227. Oncken CA, Hatsukami DK, Lupo VR et al. Effects of short-term use of nicotine gum in pregnant smokers. Clin Pharmacol Ther. 1996; 59:654-61. [IDIS 368550] [PubMed 8681490]

228. Wright LN, Thorp JM Jr., Kuller JA et al. Transdermal nicotine replacement in pregnancy: maternal pharmacokinetics and fetal effects. Am J Obstet Gynecol. 1997; 176:1090-4. [IDIS 387752] [PubMed 9166173]

229. Sanchez P, Ducasse JL, Lapeyre-Mestre M et al. Nicotine poisoning as a cause of cardiac arrest? Clin Toxicol. 1996; 34:475-6. Letter. (IDIS 372635)

230. Woolf A, Burkhart K, Caraccio T et al. Self-poisoning among adults using multiple transdermal nicotine patches. J Toxicol Clin Toxicol. 1996; 34:691-8. [IDIS 377487] [PubMed 8941198]

231. van de Klauw MM, Hillo EV, van den Berg WHHW et al. Vasculitis attributed to the nicotine patch (Nicotinell). Br J Dermatol. 1996; 134:361-4. [IDIS 361000] [PubMed 8746358]

232. Riche G, Nighoghossian N, Trouillas P. Intracerebral haematoma after application of nicotine patch. Lancet. 1995; 346:777-8. [IDIS 353137] [PubMed 7658896]

233. Foulds J, Toone B. A case of nicotine psychosis? Addiction. 1995; 90:435-7.

234. Marston GM, Cormac ID. Nicotine patches and paranoid psychosis. Irish Journal of Psychological Medicine. 1995; 12:70-1.

235. Mogadam M. Transdermal nicotine for ulcerative colitis. Ann Intern Med. 1997; 127:491-2. [IDIS 391399] [PubMed 9313011]

236. Guslandi M, Tittobello A. Transdermal nicotine for ulcerative colitis. Ann Intern Med. 1997; 127:492. [IDIS 391401] [PubMed 9313013]

237. Sandborn WJ, Tremaine WJ, Hurt RD. Transdermal nicotine for ulcerative colitis. Ann Intern Med. 1997; 127:492-3. [IDIS 391401] [PubMed 9313013]

238. Homsy W, Yan K, Houle JM et al. Plasma levels of nicotine and safety of smokers wearing transdermal delivery systems during multiple simultaneous intake of nicotine and during exercise. J Clin Pharmacol. 1997; 37:728-36. [IDIS 391447] [PubMed 9378845]

239. Anonymous. Nicotine patches and exercise. Can Med Assoc J. 1996; 154:61-2.

240. Glaxo Wellcome Inc. Zyban (bupropion hydrochloride) sustained-release tablets prescribing information. Research Triangle Park, NC; 1997 May.

241. Cromwell J, Bartosch WJ, Fiore MC et al. Cost-effectiveness of the clinical practice recommendations in the AHCPR guideline for smoking cessation. JAMA. 1997; 278:1759-66. [IDIS 395514] [PubMed 9388153]

242. Benowitz NL. Treating tobacco addiction–nicotine or no nicotine? N Engl J Med. 1997; 337:1230-1. Editorial.

243. Hurt RD, Sachs DPL, Glover ED et al. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997; 337:1195-202. [IDIS 393231] [PubMed 9337378]

244. McNeil Consumer Products Co. Nicotrol inhaler (nicotine inhalation system) prescribing information. Fort Washington, PA; 1998.

245. Hjalmarson A, Nilsson F, Sjostrom L et al. The nicotine inhaler in smoking cessation. Arch Intern Med. 1997; 157:1721-8. [IDIS 391078] [PubMed 9250233]

246. Tonnesen P, Norregaard J, Mikkelsen K et al. A double-blind trial of a nicotine inhaler for smoking cessation. JAMA. 1993; 269:1268-71. [IDIS 310480] [PubMed 8437304]

247. Molander L, Lunell E, Andersson SB et al. Dose released and absolute bioavailability of nicoyine from a nicotine vapor inhaler. Clin Pharmacol Ther. 1996; 59:394-400. [IDIS 364408] [PubMed 8612383]

248. Bergström M, Nordberg A, Lunell E et al. Regional deposition of inhaled 11-nicotine vapor in the human airway as visulaized by positron emission tomography. Clin Pharmacol Ther. 1995; 57:309-17. [IDIS 345087] [PubMed 7697948]

249. Lunell E, Bergström M, Antoni B et al. Nicotine deposition and body distribution from a nicotine inhaler and a cigarette studies with positron emission tomography, Clin Pharmacol Ther. 1996; 59:593-4. Letter.

250. McNeil Consumer Products Co. Nicotrol inhaler (nicotine inhalation system) patient information. Fort Washington, PA; 1998.

251. Russell MAH, Jarvis MJ, Sutherland G et al. Nicotine replacement in smoking cessation: pharmacokinetic considerations. JAMA. 1992; 23:169-72.

252. Schneider NG, Lunell E, Olmstead RE et al. Clinical pharmacokinetics of nasal nicotine delivery: a review and comparison with other nicotine systems. Clin Pharmacokinet. 1996; 31:65-80. [PubMed 8827400]

253. Curry SJ, Grothaus LC, McAfee T et al. Use and cost effectiveness of smoking-cessation services under four insurance plans in a health maintenance organization. N Engl J Med. 1998; 339:673-9. [IDIS 411008] [PubMed 9725926]

254. Eliasson B, Taskinen MR, Smith U. Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance. Circulation. 1996; 94:878-81. [IDIS 372164] [PubMed 8790020]

255. Schuh KJ, Schuh LM, Henningfield JE et al. Nicotine nasal spray and vapor inhaler: abuse liability assessment. Psycopharmacology (Berl). 1997; 130:352-61.

256. Ryan TJ, Antman EM, Brooks NH et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction. 1999 update: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). From website.

257. Fiore MC, Bailey WC, Cohen SJ et al. Treating tobacco use and dependence: clinical practice guideline. Rockville, MD: US Department of Health and Human Services, Public Health Service. 2000 Jun.

258. The Tobacco Use and Dependence Clinical Practice Guideline Panel, Staff, and Consortium Representatives. A clinical practice guideline for treating tobacco use and dependence: a US Public Health Service report. JAMA. 2000; 283:3244-54. [IDIS 449174] [PubMed 10866874]

259. Anon. FDA warns sellers of nicotine lollipops & lip balm that their products are illegal. FDA Talk Paper. Rockville, MD: Food and Drug Administration; 2002 Apr 10. From the FDA website: ()

260. GlaxoSmithKline. Facts about: Commit lozenge. From website . Accessed 2002 Dec.

261. Ganley C, Rappaport B, US Department of Health and Human Services. Letter to David Schifkovitz, Director, Regulatory Affairs, GlaxoSmithKline regarding NDA 21-330 (NDA submission for Commit [nicotine polacrilex lozenge]). Posted on US Food and Drug Administration website 2002 Nov 18.

262. Pharmacia. Nicotrol helps beat cigarettes—one craving at a time! From Pharmacia website. 2002.

263. Shiffman S, Dresler CM, Hajek P et al. Efficacy of nicotine lozenge for smoking cessation. Arch Intern Med. 2002; 162:1267-76. [IDIS 482301] [PubMed 12038945]

264. GlaxoSmithKline Consumer Healthcare. Commit (nicotine polacrilex lozenges) patient information. Pittsburgh, PA; 2002.

265. Pfizer Consumer Healthcare. Nicotrol inhaler (nicotine inhalation system) prescribing information. Morris Plains, NJ; 2005 Feb.

a. AHFS drug information 2006. McEvoy GK, ed. Nicotine. Bethesda, MD: American Society of Health-System Pharmacists; 2006:1394-1411.

b. GlaxoSmithKline Consumer Healthcare, L.P. Nicoderm CQ (nicotine transdermal system) user's guide. Moon Township, PA; 2005.

c. GlaxoSmithKline Consumer Healthcare, L.P. Nicorette (nicotine polacrilex gum) user's guide. Moon Township, PA; 2001.

d. Pfizer Consumer Healthcare. Nicotrol NS (nicotine nasal spray) patient information. Morris Plains, NJ. 2005 Feb.

e. Pfizer Consumer Healthcare. Nicotrol NS (nicotine nasal spray) prescribing information. Morris Plains, NJ. 2005 Feb.

g. Pfizer Consumer Healthcare. Nicotrol inhaler (nicotine inhalation system) patient information. Morris Plains, NJ; 2005 Aug.

h. GlaxoSmithKline Consumer Healthcare. Commit (nicotine polacrilex lozenges) patient information. Pittsburgh, PA; 2005.

i. Novartis Consumer Health, Inc. Habitrol (nicotine transdermal system) product information. From website: Accessed 2007 Feb 6.

Hide
(web5)