Nicotine (Monograph)

Brand names: Commit, Nicoderm CQ, Nicorette, Nicotrol Inhaler, Nicotrol NS
Drug class:
- 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

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 ⁴⁴ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹¹⁵ ¹¹⁶ ¹¹⁹ ¹²⁶ ¹³¹ ¹⁴⁴ ¹⁴⁸ ¹⁴⁹ ¹⁶⁷ ¹⁹³ ¹⁹⁴ ¹⁹⁵ ¹⁹⁶ ²⁵⁸ ^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;¹ ¹⁹⁰ ²⁶³ ²⁶⁴ 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 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

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.¹ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹²⁸ ¹⁹¹ ¹⁹⁴ ¹⁹⁵ ¹⁹⁶ ²⁴⁴ ²⁶⁴ 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 acetaminophen^e	Decrease dosage of acetaminophen as required^e
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 required^e
Adrenergic antagonists (e.g., prazosin, labetalol)	Smoking cessation may decrease circulating plasma concentrations of catecholamines¹	Decrease dosage of adrenergic antagonists as required^e
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 required^e
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 required^e
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 needed^e
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 required^e 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 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

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, or 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 nicotine for 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 nicotine replacement 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 blood pressure, 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.

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

† 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].

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. http://www.ncbi.nlm.nih.gov/pubmed/7000247?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7427329?dopt=AbstractPlus

7. Jarvis MJ, Raw M, Russell MAH et al. Randomized controlled trial of nicotine chewing-gum. BMJ. 1982; 285:537-40. http://www.ncbi.nlm.nih.gov/pubmed/6809161?dopt=AbstractPlus

8. Fagerstrom K-O. A comparison of psychological and pharmacological treatment in smoking cessation. J Behav Med. 1982; 5:343-51. http://www.ncbi.nlm.nih.gov/pubmed/7131548?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6666689?dopt=AbstractPlus

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

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. http://www.ncbi.nlm.nih.gov/pubmed/6416593?dopt=AbstractPlus

12. Russell MAH, Feyerabend C. Cigarette smoking: a dependence on high-nicotine boli. Drug Metab Rev. 1978; 8:29-57. http://www.ncbi.nlm.nih.gov/pubmed/31270?dopt=AbstractPlus

13. Kalter H, Warkany J. Congenital malformations (second of two parts). N Engl J Med. 1983; 308:491-7 (IDIS 165815) http://www.ncbi.nlm.nih.gov/pubmed/6337336?dopt=AbstractPlus

14. Johnston C. Cigarette smoking and the outcome of human pregnancies: a status report on the consequences. Clin Toxicol. 1981; 18:189-209. http://www.ncbi.nlm.nih.gov/pubmed/7226732?dopt=AbstractPlus

15. Landesman-Dwyer S, Emanuel I. Smoking during pregnancy. Teratology. 1979; 19:119-26. http://www.ncbi.nlm.nih.gov/pubmed/377552?dopt=AbstractPlus

16. Abel EL. Smoking during pregnancy: a review of effects on growth and development of offspring. Hum Biol. 1980; 52:593-625. http://www.ncbi.nlm.nih.gov/pubmed/7009384?dopt=AbstractPlus

17. Gennser G, Marsal K, Brantmark B. Maternal smoking and fetal breathing movements. Am J Obstet Gynecol. 1975; 123:861-7. http://www.ncbi.nlm.nih.gov/pubmed/1106202?dopt=AbstractPlus

18. Dougherty CRS, Jones AD. The determinants of birth weight. Am J Obstet Gynecol. 1982; 144:190-200. http://www.ncbi.nlm.nih.gov/pubmed/7114129?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6846423?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/686089?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/708655?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/5017304?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/55649?dopt=AbstractPlus

25. Ferno O, Lichtneckert SJA, Lundgren CEG. A substitute for tobacco smoking. Psychopharmacologia. 1973; 31:201-4. http://www.ncbi.nlm.nih.gov/pubmed/4732726?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7047783?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/779926?dopt=AbstractPlus

30. Brantmark B, Ohlin O, Westling H. Nicotine containing chewing gum as an anti-smoking aid. Psychopharmacologia. 1973; 31:191-200. http://www.ncbi.nlm.nih.gov/pubmed/4581737?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/382765?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/5475342?dopt=AbstractPlus

33. Glantz LA. Nicotine chewing gum not for all smokers. Clin Pharm. 1984; 3:236. http://www.ncbi.nlm.nih.gov/pubmed/6734086?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7111654?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/4552162?dopt=AbstractPlus

39. Rosenberg J, Benowitz NL, Jacob P et al. Disposition kinetics and effects of intravenous nicotine. Clin Pharmacol Ther. 1980; 28:517-22. http://www.ncbi.nlm.nih.gov/pubmed/7408411?dopt=AbstractPlus

40. Benowitz NL, Kuyt F, Jacob P et al. Cotinine disposition and effects. Clin Pharmacol Ther. 1983; 34:604-11. http://www.ncbi.nlm.nih.gov/pubmed/6627820?dopt=AbstractPlus

41. Langone JJ, Gjika HB, Van Vunakis H. Nicotine and its metabolites: radioimmunoassays for nicotine and cotinine. Biochemistry. 1973; 12:5025-30. http://www.ncbi.nlm.nih.gov/pubmed/4761980?dopt=AbstractPlus

42. Evans D, Lane DS. Long-term outcome of smoking cessation workshops. Am J Public Health. 1980; 70:725-7. http://www.ncbi.nlm.nih.gov/pubmed/7386710?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6777804?dopt=AbstractPlus

47. Fee WM, Stewart MJ. A controlled trial of nicotine chewing gum in a smoking withdrawal clinic. Practitioner. 1982; 226:148-51. http://www.ncbi.nlm.nih.gov/pubmed/7043437?dopt=AbstractPlus

48. British Thoracic Society. Comparison of four methods of smoking withdrawal in patients with smoking related diseases. BMJ. 1983; 286:595-7. http://www.ncbi.nlm.nih.gov/pubmed/6402162?dopt=AbstractPlus

49. Anon. Nicotine gum. Med Lett Drugs Ther. 1984; 26:47-8. http://www.ncbi.nlm.nih.gov/pubmed/6717371?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6647522?dopt=AbstractPlus

52. Henningfield JE, Goldberg SR. Nicotine as a reinforcer in human subjects and laboratory animals. Pharmacol Biochem Behav. 1983; 19:989-92. http://www.ncbi.nlm.nih.gov/pubmed/6657732?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/349132?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7297412?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1135877?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/476401?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6375499?dopt=AbstractPlus

68. Christen AG, McDonald JL, Olson BL. Efficacy of nicotine chewing gum in facilitating smoking cessation. J Am Dent Assoc. 1984; 108:594-7. http://www.ncbi.nlm.nih.gov/pubmed/6373886?dopt=AbstractPlus

69. Anon. Smoking and cancer. MMWR Morb Mortal Wkly Rep. 1982; 31:77-80. http://www.ncbi.nlm.nih.gov/pubmed/6801462?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6472348?dopt=AbstractPlus

71. Lees AJ. Hemidystonia relieved by nicotine. Lancet. 1984; 2:871. http://www.ncbi.nlm.nih.gov/pubmed/6148600?dopt=AbstractPlus

72. Anon. Dental effects of nicotine gum. Med Lett Drugs Ther. 1984; 26:98. http://www.ncbi.nlm.nih.gov/pubmed/6384754?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/4056988?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3887912?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2857369?dopt=AbstractPlus

78. Hughes JR, Hatsukami DK, Pickens RW et al. Effect of nicotine on the tobacco withdrawal syndrome. Psychopharmacology (Berl). 1984; 83:82-7. http://www.ncbi.nlm.nih.gov/pubmed/6429705?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6589006?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6741676?dopt=AbstractPlus

81. Shapiro J. Nicotine chewing gum in general practice. BMJ. 1984; 289:1308. http://www.ncbi.nlm.nih.gov/pubmed/6437528?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/6437528?dopt=AbstractPlus

84. Marshall A, Raw M. Nicotine chewing gum in general practice: effect of follow up appointments. BMJ. 1985; 290:1397-8. http://www.ncbi.nlm.nih.gov/pubmed/3922510?dopt=AbstractPlus

85. Jamrozik K, Fowler G, Vessey M et al. Placebo controlled trial of nicotine chewing gum in general practice. BMJ. 1984; 289:794-7. http://www.ncbi.nlm.nih.gov/pubmed/6434084?dopt=AbstractPlus

86. American College of Physicians Health and Public Policy Committee. Methods for stopping cigarette smoking. Ann Intern Med. 1986; 105:281-91. http://www.ncbi.nlm.nih.gov/pubmed/3729208?dopt=AbstractPlus

87. Hughes JR, Hatsukami DK, Skoog KP. Physical dependence on nicotine in gum: a placebo substitution trial. JAMA. 1986; 255:3277-9. http://www.ncbi.nlm.nih.gov/pubmed/3712681?dopt=AbstractPlus

88. West RJ, Russell MAH. Effects of withdrawal from long-term nicotine gum use. Psychol Med. 1985; 15:891-3. http://www.ncbi.nlm.nih.gov/pubmed/4080892?dopt=AbstractPlus

89. Hjalmarson AIM. Effect of nicotine chewing gum in smoking cessation: a randomized, placebo-controlled, double-blind study. JAMA. 1984; 252:2835-8. http://www.ncbi.nlm.nih.gov/pubmed/6387207?dopt=AbstractPlus

90. Hughes JR, Miller SA. Nicotine gum to help stop smoking. JAMA. 1984; 252:2855-8. http://www.ncbi.nlm.nih.gov/pubmed/6387208?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3563596?dopt=AbstractPlus

93. Lee BL, Benowitz NL, Jacob P III. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med. 1987; 106:553-5. http://www.ncbi.nlm.nih.gov/pubmed/3826954?dopt=AbstractPlus

94. Benowitz NL, Jacob P III, Savanapridi C. Determinants of nicotine intake while chewing nicotine polacrilex gum. Clin Pharmacol Ther. 1987; 41:467-73. http://www.ncbi.nlm.nih.gov/pubmed/3829583?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3336380?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/3411739?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2294395?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2395197?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2725117?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2071260?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2612544?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2311334?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2012458?dopt=AbstractPlus

112. Rose JE, Levin ED, Behm FM et al. Transdermal nicotine facilitates smoking cessation. Clin Pharmacol Ther. 1990; 47:323-30. http://www.ncbi.nlm.nih.gov/pubmed/2178852?dopt=AbstractPlus

113. Abelin T, Buehler A, Müller P et al. Controlled trial of transdermal nicotine patch in tobacco withdrawal. Lancet. 1989; 1:7-9. http://www.ncbi.nlm.nih.gov/pubmed/2563045?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2657276?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2255215?dopt=AbstractPlus

116. Peter JA. Nicotine-replacement therapy in cessation of smoking. Mayo Clin Proc. 1990; 65:1619-23. http://www.ncbi.nlm.nih.gov/pubmed/2255223?dopt=AbstractPlus

117. Russell MAH. The future of nicotine replacement. Br J Addict. 1991; 86:653-8. http://www.ncbi.nlm.nih.gov/pubmed/1859935?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2057036?dopt=AbstractPlus

119. Morgan GD, Villagra VG. The nicotine transdermal patch: a cautionary note. Ann Intern Med. 1992; 116:424. http://www.ncbi.nlm.nih.gov/pubmed/1736778?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1914363?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/4042528?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1891488?dopt=AbstractPlus

127. Ranade VV. Drug delivery systems, 6, transdermal drug delivery. J Clin Pharmacol. 1991; 31:401-18. http://www.ncbi.nlm.nih.gov/pubmed/2050824?dopt=AbstractPlus

128. Benowitz NL. Nicotine replacement therapy during pregnancy. JAMA. 1991; 266:3174-7. http://www.ncbi.nlm.nih.gov/pubmed/1956108?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1827299?dopt=AbstractPlus

131. Varma JR. Transdermal nicotine patch for smoking cessation. N Engl J Med. 1992; 326:344. http://www.ncbi.nlm.nih.gov/pubmed/1728742?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1728741?dopt=AbstractPlus

135. Hartman N, Leong GB, Glynn SM et al. Transdermal nicotine and smoking behavior in psychiatric patients. Am J Psychiatry. 1991; 148:374-5. http://www.ncbi.nlm.nih.gov/pubmed/1992843?dopt=AbstractPlus

136. Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation: six-month results from two multicenter controlled clinical trials. JAMA. 1991; 266:3133-8. http://www.ncbi.nlm.nih.gov/pubmed/1956099?dopt=AbstractPlus

137. Anon. Nicotine patches. Med Lett Drugs Ther. 1992; 34:37-8. http://www.ncbi.nlm.nih.gov/pubmed/1556994?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1548823?dopt=AbstractPlus

140. Benowitz NL. Nicotine replacement therapy during pregnancy. JAMA. 1992; 267:1922. http://www.ncbi.nlm.nih.gov/pubmed/1548823?dopt=AbstractPlus

141. Minneker-Hügel E, Unland H, Buchkremer G. Behavioral relapse prevention strategies in smoking cessation. Int J Addict. 1992; 27:627-34. http://www.ncbi.nlm.nih.gov/pubmed/1601540?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1634647?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1382940?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1526077?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1475232?dopt=AbstractPlus

147. Schneider NG. Nicotine therapy in smoking cessation. Pharmacokinetic considerations. Clin Pharmacokinet. 1992; 23:169-72. http://www.ncbi.nlm.nih.gov/pubmed/1511534?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1304736?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8440767?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8440766?dopt=AbstractPlus

152. Sutherland G, Russell MA, Stapleton J et al. Nasal nicotine spray: a rapid nicotine delivery system. Psychopharmacology (Berl). 1992; 108:512-8. http://www.ncbi.nlm.nih.gov/pubmed/1410168?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1410169?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1815971?dopt=AbstractPlus

155. Lee EW, D’Alonzo GE. Cigarette smoking, nicotine addiction, and its pharmacologic treatment. Arch Intern Med. 1993; 153:34-48. http://www.ncbi.nlm.nih.gov/pubmed/8422199?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2117147?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1570391?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2725119?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2725120?dopt=AbstractPlus

162. Tonnesen P, Norregaard J, Sawe U et al. Recycling with nicotine patches in smoking cessation. Addiction. 1993; 88:533-9. http://www.ncbi.nlm.nih.gov/pubmed/8485431?dopt=AbstractPlus

163. Bircher AJ, Howald H, Rufli T. Adverse skin reactions to nicotine in a transdermal therapeutic system. Contact Dermatitis. 1991; 25:230-6. http://www.ncbi.nlm.nih.gov/pubmed/1839264?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8464119?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/2568138?dopt=AbstractPlus

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.

171. Gora ML. Nicotine transdermal systems. Ann Pharmacother. 1993; 27:742-50. http://www.ncbi.nlm.nih.gov/pubmed/8329798?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/1859910?dopt=AbstractPlus

174. Corrigall WA. Understanding brain mechanisms in nicotine reinforcement. Br J Addict. 1991; 86:507-10. http://www.ncbi.nlm.nih.gov/pubmed/1859913?dopt=AbstractPlus

175. Stolerman IP. Behavioural pharmacology of nicotine: multiple mechanisms. Br J Addict. 1991; 86:533-6. http://www.ncbi.nlm.nih.gov/pubmed/1650269?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8366189?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8486002?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8601956?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8201739?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8601960?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7575051?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7640544?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8179456?dopt=AbstractPlus

201. Sutherland G, Stapleton JA, Russell MAH et al. Randomised controlled trial of nasal nicotine spray in smoking cessation. Lancet. 1992; 340:324-9. http://www.ncbi.nlm.nih.gov/pubmed/1353803?dopt=AbstractPlus

202. Hjalmarson A, Franzon M, Westin A et al. Effect of nicotine nasal spray on smoking cessation. Arch Intern Med. 1994; 154:2567-72. http://www.ncbi.nlm.nih.gov/pubmed/7979853?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8555958?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9054280?dopt=AbstractPlus

205. Bonapace CR, Mays DA. The effect of mesalamine and nicotine in the treatment of inflammatory bowel disease. Ann Pharmacother. 1997; 31:907-12. http://www.ncbi.nlm.nih.gov/pubmed/9220055?dopt=AbstractPlus

206. Pullan RD, Rhodes J, Ganesh S et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994; 330:811-5. http://www.ncbi.nlm.nih.gov/pubmed/8114833?dopt=AbstractPlus

207. Hanauer SB. Nicotine for colitis—the smoke has not yet cleared. N Engl J Med. 1994; 330:856-7. http://www.ncbi.nlm.nih.gov/pubmed/8114839?dopt=AbstractPlus

208. Kennedy LD. Nicotine therapy for ulcerative colitis. Ann Pharmacother. 1996; 30:1022-3. http://www.ncbi.nlm.nih.gov/pubmed/8876866?dopt=AbstractPlus

209. Rhodes J, Thomas G. Nicotine treatment in ulcerative colitis: current status. Drugs. 1995; 49:157-60. http://www.ncbi.nlm.nih.gov/pubmed/7729324?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7885427?dopt=AbstractPlus

211. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol. 1997; 29:1422-31. http://www.ncbi.nlm.nih.gov/pubmed/9180099?dopt=AbstractPlus

212. Ottervanger JP, Festen JM, de Vries AG et al. Acute myocardial infarction while using the nicotine patch. Chest. 1995; 107:1765-6. http://www.ncbi.nlm.nih.gov/pubmed/7781384?dopt=AbstractPlus

213. Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994; 120:695. http://www.ncbi.nlm.nih.gov/pubmed/8135462?dopt=AbstractPlus

214. Jackson M. Cerebral arterial narrowing with nicotine patch. Lancet. 1993; 342:236-7. http://www.ncbi.nlm.nih.gov/pubmed/8100951?dopt=AbstractPlus

215. Pierce JR Jr. Stroke following application of a nicotine patch. Ann Pharmacother. 1994; 28:402. http://www.ncbi.nlm.nih.gov/pubmed/8193434?dopt=AbstractPlus

216. Kafka HP. Heart attacks, smoking, and the nicotine patch. Ann intern Med. 1994; 121:389. http://www.ncbi.nlm.nih.gov/pubmed/8042844?dopt=AbstractPlus

217. Mittleman MA. Smoking while wearing a nicotine patch. Ann Intern Med. 1995; 122:476-7. http://www.ncbi.nlm.nih.gov/pubmed/7857004?dopt=AbstractPlus

218. Warner JG Jr, Little WC. Myocardial infarction in a patient who smoked while wearing a nicotine patch. Ann Intern Med. 1994; 120:695. http://www.ncbi.nlm.nih.gov/pubmed/8135462?dopt=AbstractPlus

219. Lagrue G, Verra F, Lebargy F. Nicotine patches and vascular risks. Lancet. 1993; 342:564. http://www.ncbi.nlm.nih.gov/pubmed/8102710?dopt=AbstractPlus

220. Jackson M. Nicotine patches and vascular risks. Lancet. 1993; 342:564. http://www.ncbi.nlm.nih.gov/pubmed/8102710?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8943160?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9207632?dopt=AbstractPlus

223. Kottke TE. Managing nicotine dependence. J Am Coll Cardiol. 1997; 30:131-2. http://www.ncbi.nlm.nih.gov/pubmed/9207633?dopt=AbstractPlus

224. Rigotti NA, Eagle KA. Atrial fibrillation while chewing nicotine gum. JAMA. 1986; 255:1018. http://www.ncbi.nlm.nih.gov/pubmed/3945010?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8620719?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8681490?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9166173?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8941198?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8746358?dopt=AbstractPlus

232. Riche G, Nighoghossian N, Trouillas P. Intracerebral haematoma after application of nicotine patch. Lancet. 1995; 346:777-8. http://www.ncbi.nlm.nih.gov/pubmed/7658896?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9313011?dopt=AbstractPlus

236. Guslandi M, Tittobello A. Transdermal nicotine for ulcerative colitis. Ann Intern Med. 1997; 127:492. http://www.ncbi.nlm.nih.gov/pubmed/9313013?dopt=AbstractPlus

237. Sandborn WJ, Tremaine WJ, Hurt RD. Transdermal nicotine for ulcerative colitis. Ann Intern Med. 1997; 127:492-3. http://www.ncbi.nlm.nih.gov/pubmed/9313013?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9378845?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9388153?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9337378?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9250233?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8437304?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8612383?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/7697948?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8827400?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/9725926?dopt=AbstractPlus

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. http://www.ncbi.nlm.nih.gov/pubmed/8790020?dopt=AbstractPlus

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) and http://www.americanheart.org. http://www.acc.org/clinical/guidelines

257. Fiore MC, Jaén CR, Baker TB, et al. Treating tobacco use and dependence: 2008 update. Clinical Practice Guideline. Rockville, MD: US Department of Health and Human Services, Public Health Service. 2008 May.

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. http://www.ncbi.nlm.nih.gov/pubmed/10866874?dopt=AbstractPlus

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: http://www.fda.gov/bbs/topics/ANSWERS/2002/ANS01144.html

260. GlaxoSmithKline. Facts about: Commit lozenge. From website. Accessed 2002 Dec. http://www.commitlozenge.com

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. http://www.ncbi.nlm.nih.gov/pubmed/12038945?dopt=AbstractPlus

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.

266. Hajek P, Phillips-Waller A, Przulj D et al. A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. N Engl J Med. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30699054?dopt=AbstractPlus

267. Food and Drug Administration. Regulation of electronic nicotine delivery systems (including E-Cigarettes) and the continuum of nicotine-delivering products. Rules and regulations. [21 CFR Parts 1100, 1140, and 1143] Fed Regist. 2016; 81(90): 29028--724.

268. Borrelli B, O'Connor GT. E-Cigarettes to Assist with Smoking Cessation. N Engl J Med. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30699299?dopt=AbstractPlus

269. Bullen C, Howe C, Laugesen M et al. Electronic cigarettes for smoking cessation: a randomised controlled trial. Lancet. 2013; 382:1629-37. http://www.ncbi.nlm.nih.gov/pubmed/24029165?dopt=AbstractPlus

270. Drazen JM, Morrissey S, Campion EW. The Dangerous Flavors of E-Cigarettes. N Engl J Med. 2019; http://www.ncbi.nlm.nih.gov/pubmed/30699053?dopt=AbstractPlus

271. Hartmann-Boyce J, McRobbie H, Bullen C et al. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2016; 9:CD010216. http://www.ncbi.nlm.nih.gov/pubmed/27622384?dopt=AbstractPlus

272. National Academies of Sciences, Engineering, and Medicine 2018. Public health consequences of e-cigarettes. Washington DC: The National Academies Press https://doi.org/10.17226/24952

273. Livingston CJ, Freeman RJ, Costales VC et al. Electronic Nicotine Delivery Systems or E-cigarettes: American College of Preventive Medicine's Practice Statement. Am J Prev Med. 2019; 56:167-178. http://www.ncbi.nlm.nih.gov/pubmed/30573147?dopt=AbstractPlus

274. American Psychiatric Association. DSM-V™: diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013: 571-4.

275. Food and Drug Administration. Clarification of when products made or derived from tobacco are regulated as drugs, devices, or combination products; amendments to regulations regarding “intended uses”. Final Rule. [21 CFR Parts 201, 801, and 1100] Fed Regist. 2017; 82(5): 2193-217.

a. AHFS drug information 2020. McEvoy GK, ed. Nicotine. Bethesda, MD: American Society of Health-System Pharmacists; 2020.

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. http://www.habitrol.com

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