Nicotine

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}

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 skin^{43 101 129} on the trunk or upper outer arm^{101 102 103 104 129 167 188 189 257} 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}