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Nicotine (Systemic)


VA CLASSIFICATION
Primary: AD600

Commonly used brand name(s): Habitrol; NicoDerm CQ; Nicoderm; Nicorette; Nicorette Plus; Nicotrol; Prostep.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Smoking cessation adjunct—

Indications

Accepted

Nicotine dependence (treatment adjunct)—Nicotine chewing gum and nicotine transdermal systems are indicated as temporary aids for the cigarette smoker who wants to give up smoking. They serve as alternative sources of nicotine and provide relief of nicotine withdrawal symptoms in nicotine-dependent individuals who are acutely withdrawing from cigarette smoking. {07}4 {07}3 {07}2 {07}1 {07}0 {06}9 {06}8 {06}7 {06}6 {06}5 {06}4 {06}3
—It is recommended that nicotine chewing gum and transdermal systems be used in conjunction with comprehensive behavior modification programs that include education, counseling, and psychological support.
—Generally, smokers who have a strong physical nicotine dependence are more likely to benefit from the use of these nicotine products. Smoking withdrawal effects such as irritability, drowsiness, fatigue, headache, and nicotine craving are lessened with their use. {06}2 {06}1 {06}0 {25}9

Acceptance not established
Nicotine, in conjunction with a 5-aminosalicylic acid compound or other conventional maintenance therapy, has been used in the treament of ulcerative colitis to ameliorate the condition and relieve symptoms {25}8 {25}7 {25}6 {25}5 {25}4 {25}3 but not induce remission {25}2 {25}1 in nonsmoking patients with mild to moderate ulcerative colitis. However, there are insufficient data to support the safety and efficacy of nicotine for this use. {25}0 (Evidence rating: I)

Nicotine, in conjunction with an antipsychotic such as haloperidol, has been used in the treatment of Gilles de la Tourette"s syndrome to decrease the severity and frequency of tics and vocalizations of Tourette"s syndrome. {22}9 {22}8 {22}7 {22}6 {22}5 {22}4 {22}3 {22}2 However, there are insufficient data to support the safety and efficacy of nicotine for this use. {22}1 (Evidence rating: II)


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Tobacco plant. {22}0 {06}9 {06}8 {06}7
Molecular weight—
    Nicotine: 162.24 {06}6

Ionization constants—
    pKa 1: 7.84 {06}5 {06}4 {06}3
    pKa 2: 3.04 {06}2 {06}1 {06}0

Mechanism of action/Effect:


Smoking cessation adjunct:

Nicotine acts as an agonist at the nicotinic cholinergic receptors at the autonomic ganglia, {25}9 {25}8 {25}7 {25}6 {25}5 in the adrenal medulla, at neuromuscular junctions, and in the brain. {25}4 {25}3 {25}2Nicotine's positive reinforcing properties are believed to be the result of the release of neurotransmitters including acetylcholine, beta-endorphin, dopamine, norepinephrine, serotonin, and others that mediate pleasure, arousal, elevated mood, appetite, and other desirable psychological states. {25}1

When the gum is chewed, nicotine is displaced from polacrilex by alkaline saliva. {25}0 {22}9



Other actions/effects:

Has actions on the chemoreceptors of the aortic and carotid bodies, {22}8 {22}7 {22}6 resulting in reflex vasoconstriction, tachycardia, elevated blood pressure, and stimulation of respiration. {22}5 {22}4 {22}3 {22}2 {22}1 {22}0

Stimulates sympathetic ganglia and adrenal medulla, {22}9 causing release of catecholamines, {22}8 {22}7 {22}6 {22}5 resulting in direct sympathomimetic effects on the heart and peripheral vasculature. {22}4

Has actions that tend to reduce blood pressure and heart rate. In low concentrations, stimulates certain chemoreceptors in the pulmonary and coronary circulation, leading to reflex bradycardia and hypotension.

Causes release of antidiuretic hormone (ADH) by stimulation of hypothalamus.

Stimulation of emetic chemoreceptor trigger zone of medulla oblongata and vagal reflex activation may result in vomiting.

Parasympathetic stimulation increases tone and motor activity of the gastrointestinal tract, leading to nausea, vomiting, and occasionally diarrhea.

Effects of nicotine on exocrine glands cause an initial stimulation followed by inhibition of salivary and bronchial secretions.

Action on the central nervous system (CNS) may result in respiratory failure due to both central paralysis and peripheral blockade of muscles of respiration.

Absorption:


Chewing gum:

Buccal mucosa: Absorption enhanced by buffering of gum to pH 8.5; rate of absorption is slower than from lungs during smoking.

Stomach: Not absorbed in significant amounts when gum is swallowed because of poor release of nicotine from gum in acidic pH of stomach. {22}3



Transdermal systems:

Skin: Well absorbed. {22}2 {22}1


Distribution:

Nicotine passes into and accumulates in {22}0 breast milk. {29}9 {29}8 {29}7 {29}6 {29}5 {29}4 {29}3 {29}2 {29}1 {29}0 The milk-to-plasma ratio average is 2.9:1. {29}9 {29}8 {29}7 {29}6

The volume of distribution following intravenous administration is approximately 2 to 3 L per kg of body weight. {29}5 {29}4 {29}3

Protein binding:

Very low (< 5%). {29}2 {29}1 {29}0

Biotransformation:

Primarily hepatic; {29}9 {29}8 {29}7 {29}6 {29}5 {29}4 {29}3 smaller amounts are metabolized in the kidneys {29}2 {29}1 {29}0 {27}9 {27}8 {27}7 and lungs. {27}6 {27}5 {27}4 {27}3 {27}2 {27}1 More than 20 metabolites have been identified. All are believed to be less active than the parent compound. Cotinine is the primary metabolite. {27}0 {31}9 {31}8

Half-life:


Following intravenous administration:

Nicotine: 1 to 2 hours. {31}7 {31}6 {31}5 {31}4 {31}3 {31}2 {31}1 {31}0 {20}9

Cotinine: 15 to 20 hours. {20}8 {20}7 {20}6 {20}5 {20}4 {20}3



Following removal of the transdermal system, due to continued absorption from the skin depot:

3 to 4 hours. {20}2 {20}1 {20}0


Time to peak concentration:


Chewing gum:

15 to 30 minutes after start of chewing. {51}9 {51}8



Transdermal systems:

4 to 12 hours after application. {51}7 {51}6 {51}5


Peak plasma concentration


Chewing gum (following a single piece of gum chewed for 30 minutes):

5 or 10 nanograms per mL (nanograms/mL) with a 2- or 4-mg piece of gum, respectively. {51}4 {51}3



Transdermal systems:

Following application of the 14-mg-per-day system: 6 to 16 nanograms/mL. {51}2 {51}1

Following application of the 21-mg-per-day system: 13 to 19 nanograms/mL. {51}0 {27}9

Following application of the 22-mg-per-day system: 7 to 31 nanograms/mL. {27}8


Elimination:
    Renal, {27}7 {27}6 {27}5 {27}4 {27}3 {27}2 {27}1 10 {27}0 {31}9 {31}8 {31}7 {31}6 to 20% unchanged; {31}5 {31}4 {31}3 {31}2 up to 30% may be excreted unchanged in acidified urine (pH < 5) or with high urine flow rates. {31}1 {31}0 {27}9 {27}8


Precautions to Consider

Carcinogenicity

Nicotine does not appear to be carcinogenic in laboratory animals. {27}7 {27}6 {27}5 {27}4 {27}3 Inconclusive evidence suggests that cotinine, an oxidized metabolite, may be carcinogenic in rats. {27}2 {27}1 {27}0 {31}9 {31}8 {31}7

Tumorigenicity

When given in combination with tumor initiators, nicotine and its metabolites increased the incidence of tumors in hamsters and rats. {31}6 {31}5 {31}4 {31}3

Mutagenicity

Neither nicotine nor its metabolite, cotinine, was shown to be mutagenic in the Ames Salmonella test. {31}2 {31}1 {31}0 {20}9 {20}8 {20}7 {20}6 {20}5 Nicotine induced reparable DNA damage in an Escherichia coli test system. {20}4 {20}3 {20}2 {20}1 {20}0 {51}9 Nicotine was shown to be genotoxic in Chinese hamster ovary cells. {51}8 {51}7 {51}6 {51}5

Pregnancy/Reproduction
Fertility—
Impaired fertility has been demonstrated in mice following administration of nicotine. {51}4 In addition, implantation was delayed or inhibited in rats and rabbits by reduction in DNA synthesis that appears to be caused by nicotine. {51}3 {51}2 {51}1 {51}0 {25}9 {25}8 Rats treated with nicotine during the time of gestation have produced decreased litter sizes. {25}7 {25}6 {25}5 {25}4 {25}3 {25}2 {25}1

Pregnancy—
Nicotine replacement therapy is not recommended during pregnancy {25}0 {05}9 {05}8 {05}7 {05}6 {05}5 {05}4 {05}3 {05}2 and should be used only if the likelihood of smoking cessation outweighs the potential risks that continued smoking poses to the fetus. {05}1 Pregnant smokers should be encouraged to attempt smoking cessation using education and behavioral interventions before using pharmacological measures. {05}0 {06}9 {06}8 {06}7

Cigarette smoking may cause low birth weight, increased risk of spontaneous abortion, and increased perinatal mortality. {06}6 {06}5 {06}4 {06}3 Spontaneous abortion during nicotine replacement therapy has been reported, and possibly may be due to the nicotine. {06}2 {06}1 {06}0 {07}9 {07}8 {07}7 {07}6

Studies in pregnant rhesus monkeys have shown that nicotine administered intravenously decreases uterine blood flow and produces acidosis, hypercarbia, and hypotension in the fetus. {07}5 {07}4 {07}3 A study in sheep has shown that nicotine at a dose of 0.25 mg per kg of body weight administered intravenously to the ewe resulted in reduced breathing movements in the fetal lamb. {07}2 {07}1 {07}0 Teratogenicity has been demonstrated in offspring of mice given toxic doses of nicotine. {08}9 {08}8 {08}7 {08}6

Nicotine chewing gum—FDA Pregnancy Category C. {08}5

Nicotine transdermal systems—FDA Pregnancy Category D. {08}4 {08}3 {08}2 {08}1 {08}0

Breast-feeding

Nicotine is distributed into and accumulates in {25}9 breast milk {25}8 {25}7 {25}6 {25}5 {25}4 {25}3 {25}2 {25}1 and is not recommended for use by breast-feeding women {25}0 {27}9 {27}8 {27}7 {27}6.

Pediatrics

Appropriate studies on the relationship of age to the effects of nicotine have not been performed in children up to 18 years of age. {27}5 {27}4 {27}3 Safety and efficacy have not been established. {27}2 {27}1 {27}0 {28}9 {28}8 {28}7 {28}6

Small amounts of nicotine can cause serious harm in children. Even nicotine transdermal systems that have been used still contain enough nicotine to cause toxicity {28}5 in children. {28}4 {28}3 {28}2 {28}1 {28}0 {29}9 {29}8 {29}7 {29}6



Adolescents

Appropriate studies on the relationship of age to the effects of nicotine have not been performed in adolescents up to 18 years of age. However, no specific problems in nicotine-dependent adolescents have been documented to date. {29}5 Nicotine replacement therapy should be considered only when there is clear evidence of nicotine dependence and a desire to quit smoking. {29}4


Geriatrics


Studies performed in a limited number of patients 60 years of age or older have not demonstrated geriatrics-specific problems that would limit the usefulness of nicotine in the elderly. {29}3 {29}2 {29}1 {29}0


Dental

When used over an extended period of time, nicotine gum may cause severe occlusal stress because its viscosity is heavier than that of ordinary chewing gum. {24}9 Nicotine gum can cause loosening of inlays or fillings, can stick to dentures, and can cause damage to oral mucosa and natural teeth. {24}8 The use of hard sugarless candy between doses of gum is recommended to help provide oral stimulation required by some patients. {24}7 {24}6 Also, some temporomandibular joint dysfunction and pain have been associated with excessive chewing. {24}5

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also be affected by cessation of smoking.

Acetaminophen{24}4{24}3{24}2{24}1{24}0{05}9{05}8{05}7 or
» Bronchodilators, xanthine-derivative, except dyphylline{05}6{05}5{05}4{05}3{05}2{05}1{05}0{06}9{06}8{06}7{06}6{06}5{06}4{06}3{06}2 or
Caffeine{06}1{06}0{07}9{07}8{07}7{07}6{07}5 or
Imipramine{07}4{07}3{07}2{07}1{07}0{08}9{08}8{08}7 or
Oxazepam{08}6{08}5{08}4{08}3{08}2{08}1{08}0{25}9 or
Pentazocine{25}8{25}7{25}6{25}5{25}4{25}3{25}2{25}1 or
» Propoxyphene{25}0{18}{19} or
» Propranolol, and possibly other beta-adrenergic blocking agents{03}{05}{06}{07}{08}{19}{20}{25}{27}{29}    (smoking cessation may increase therapeutic effects of these agents by decreasing metabolism, thereby increasing serum concentrations; a decrease in dosage may be necessary)


» Alpha-adrenergic blocking agents,{18} such as labetalol and prazosin{06}{07}{19}{20}{25}{27}{29}    (smoking cessation may increase the therapeutic effects of these agents as a result of the decrease in circulating catecholamines; a decrease in dosage may be necessary)


» Insulin{04}{05}{06}{07}{08}{17}{19}{20}{25}{27}{29}    (smoking cessation and concurrent therapy with nicotine chewing gum, transdermal systems, or other smoking deterrents, such as lobeline sulfate and silver acetate, may increase the therapeutic effects of insulin by increasing absorption, thereby increasing serum concentrations; {28} a decrease in insulin dosage may be necessary when a patient with diabetes who is taking insulin suddenly stops smoking)


» Sympathomimetic agents, such as isoproterenol and phenylephrine{06}{07}{18}{20}{25}{27}{29}    (smoking cessation may decrease the therapeutic effects of these agents as a result of the decrease in circulating catecholamines; an increase in dosage may be necessary)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Angina pectoris, severe{01}{05}{06}{07}{08}{17}{20}{18}{19}{22}{25}{26}{27}{28}{29} or
» Cardiac arrhythmias, life-threatening{01}{05}{06}{07}{08}{17}{18}{19}{20}{22}{25}{26}{27}{28}{29} or
» Cerebrovascular accident, recent{27}{28}{29} or
» Post–myocardial infarction{01}{05}{06}{07}{08}{17}{18}{19}{20}{22}{25}{26}{27}{28}{29}    (may be exacerbated by action on heart of catecholamines released from adrenal medulla)


Risk-benefit should be considered when the following medical problems exist
Angina pectoris{01}{02}{05}{06}{07}{08}{18}{19}{25}{27}{28} or
Cardiac arrhythmias{01}{05}{06}{07}{08}{17}{18}{19}{20}{25}{27}{29} or
Diabetes, type 1{01}{05}{06}{07}{08}{17}{18}{19}{20}{25}{27}{28}{29} or
» Hypertension{01}{05}{06}{07}{08}{17}{18}{19}{20}{25}{27}{28}{29} or
Hyperthyroidism{01}{05}{06}{07}{08}{18}{19}{20}{25}{27}{28}{29} or
Myocardial infarction, history of{01}{05}{06}{07}{08}{20}{25}{27}{29} or
Pheochromocytoma{01}{05}{06}{07}{08}{18}{19}{20}{25}{27}{29} or
Vasospastic diseases, such as Buerger's disease and Prinzmetal's (or variant) angina{01}{02}{05}{06}{07}{08}{18}{19}{20}{25}{27}{28}{29}    (increases in blood pressure, heart rate, and plasma glucose concentrations may result from effects of nicotine-induced catecholamine release)

    (risk of progression to malignant hypertension in patients with accelerated hypertension {06} {07} {20} {25} {27} {29})


Peptic ulcer disease, active{06}{07}{17}{18}{19}{20}{25}{27}{28}{29}    (nicotine delays healing; caution is recommended)


Sensitivity to nicotine{01}{05}{06}{07}{08}{20}{25}{27}{28}{29} or to any component of the product{06}{25}{27}{28}{29}
For the chewing gum only (in addition to the above):
Dental problems{01}{17} or
Temporomandibular joint (TMJ) disorder{01}{17}{18}{19}    (injury to teeth or aggravation of TMJ may result from mechanical effects of chewing gum)


Esophagitis, history of{01}{02}{18}{19} or
Inflammation of mouth or throat{01}{02}{18}{19}    (may be exacerbated)


For the transdermal systems only (in addition to the above):
Skin diseases, such as atopic or eczematous dermatitis{05}{06}{07}{08}{20}{25}{27}{28}{29}    (transdermal systems may be irritating)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Evaluation of progress of smoking cessation{01}{02}{05}{08}    (recommended periodically during therapy to assess therapeutic efficacy of nicotine replacement products and to re-evaluate their use)




Side/Adverse Effects

Note: Side effects are dose-dependent; extremely high doses can produce toxic symptoms, even in nicotine-tolerant individuals.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
For chewing gum only
    
Injury{01}{02}{18}{19} or irritation{30} to mouth, teeth, or dental work

Note: Nicotine gum is stickier and of heavier viscosity than ordinary gum, making it harder to chew.



Incidence less frequent
For all nicotine replacement products
    
Hypertension {06}{18}{19}{25}{28}


Incidence rare
For all nicotine replacement products
    
Fast or irregular heartbeat {01}{06}{07}{18}{19}{25}{27}{28}{29}
    
hypersensitivity reactions, local or generalized,{05}{06}{07}{08}{18}{19}{20}{25}{28} including edema (swelling), erythema (redness), pruritus (itching), rash
or urticaria (hives)

Note: If fast or irregular heartbeat or hypersensitivity reactions occur, use of nicotine replacement products should be discontinued. {06} {07} {18} {19} {25} {27} {28} {29} Further exposure in patients who have experienced a hypersensivity reaction could result in serious allergic reactions to all forms of nicotine, including cigarettes. {06} {07} {25} {28} {29}





Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
For all nicotine replacement products
    
Headache, mild {01}{05}{06}{07}{08}{09}{18}{19}{20}{25}{27}{28}{29}{43}
    
increased appetite {02}

For chewing gum only
    
Belching —may be minimized by modifying chewing technique{01}{02}{18}{19}
    
increased watering of mouth, mild {01}{02}{18}{19}
    
jaw muscle ache {01}{18}
    
sore mouth or throat {01}{02}{18}

For transdermal systems only
    
Erythema, pruritus, and/or burning at site of application (redness, itching, and/or burning){06}{07}{08}{20}{22}{25}{27}{28}{43}—usually subsides within 24 hours{06}{07}{20}{25}{27}

Note: If erythema, pruritus, or burning at site of application is severe or persists, use of nicotine transdermal systems should be discontinued. {06} {07} {20} {25} {27} {28} {29}



Incidence less frequent or rare
For all nicotine replacement products
    
Change in sense of taste {18}{19}{27}{28}{29}
    
coughing, increased {01}{05}{06}{09}{20}{25}{27}{28}
    
dizziness or lightheadedness, mild {01}{05}{06}{07}{08}{09}{18}{19}{20}{25}{27}{28}{29}
    
drowsiness {06}{07}{08}{25}{27}{28}{43}
    
dryness of mouth {01}{02}{05}{06}{25}{27}{28}
    
dysmenorrhea (menstrual pain){05}{06}{07}{08}{20}{25}{28}
    
gastrointestinal effects, such as abdominal or stomach pain{06}{07}{20}{25}{27}{28}{47}
constipation {01}{05}{06}{07}{08}{25}{27}{28}
diarrhea {05}{06}{07}{08}{25}{27}{28}{29}
flatulence (passing of gas){27}{28}{29}, indigestion, mild {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
loss of appetite {01}{18}
and nausea or vomiting {06}{07}{18}{19}{20}{25}{27}{28}{29}{43}{47}
    
muscle or joint pain {05}{06}{07}{08}{09}{20}{25}{27}{28}{29}
    
sweating, increased {05}{07}{08}{27}{28}
    
trouble in sleeping or abnormal dreams {01}{05}{06}{07}{08}{09}{18}{19}{20}{25}{27}{28}{29}
    
unusual irritability or nervousness {01}{05}{18}{19}{20}{27}{28}

Note: If trouble in sleeping or abnormal dreams occur when the transdermal system is worn for 24 hours, it should be taken off at bedtime (after approximately 16 hours) and replaced upon arising the next day. {22}


For chewing gum only
    
Hiccups {01}{02}{18}
    
hoarseness {01}






Overdose
For specific information on the agents used in the management of nicotine overdose, see:    • Atropine in Anticholinergics/Antispasmodics (Systemic) monograph;
   • Barbiturates (Systemic) monograph;
   • Charcoal, Activated (Oral-Local)monograph;
   • Ipecac (Oral-Local) monograph;
   • Lorazepam in Benzodiazepines (Systemic) monograph; and/or
   • Sympathomimetic Agents—Cardiovascular Use (Parenteral-Systemic) monograph.


For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center {17} {22} {26} (see Poison Control Center Listing ).

The minimum lethal oral dose of nicotine for adults is reported to be 40 to 60 mg. {06} {07} {18} {19} {25} {27} {28} {29}

Overdose may occur if many pieces of gum are chewed simultaneously or in rapid succession. {18} {19} Overdose also may occur if several transdermal systems are worn simultaneously. {28} Absorption may be reduced by the early nausea and vomiting known to occur with excessive nicotine intake. If gum is swallowed without chewing, nicotine will not be released or absorbed in significant amounts because of the acid pH of the stomach.

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Early effects of overdose (in possible order of occurrence)
    
Nausea and/or vomiting {01}{02}{06}{07}{09}{17}{18}{19}{20}{22}{25}{27}{28}{29}
    
increased watering of mouth, severe {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
abdominal pain, severe {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
diarrhea, severe {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
pale skin {06}{07}{20}{25}{27}{28}{29}
    
cold sweat {01}{06}{07}{18}{19}{20}{25}{27}{29}
    
headache, severe {01}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
dizziness, severe {01}{02}{06}{07}{09}{17}{18}{19}{20}{22}{25}{27}{28}{29}
    
disturbed hearing and vision {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
tremor {06}{07}{20}{25}{27}{28}{29}
    
confusion {01}{02}{06}{07}{18}{19}{20}{25}{27}{28}{29}
    
weakness, severe {01}{06}{07}{17}{18}{19}{20}{22}{25}{27}{28}{29}

Late effects of overdose (in possible order of occurrence)
    
Extreme exhaustion {06}{07}{18}{19}{20}{25}{27}{28}{29}
    
fainting {01}{02}{18}{19}
    
hypotension {01}{06}{07}{09}{18}{19}{20}{25}{27}{29}
    
difficulty in breathing, severe {01}{02}{06}{07}{09}{18}{19}{20}{25}{27}
    
fast, weak, or irregular pulse {01}{17}{18}{19}{22}
    
seizures {01}{02}{06}{07}{09}{18}{19}{20}{25}{27}{28}{29}
    
death —due to respiratory paralysis{06}{07}{18}{19}{20}{25}{27}{28}{29} or cardiac failure{06}{07}{20}{25}{27}{28}{29}


Treatment of overdose


For chewing gum only:
To decrease absorption: In a conscious patient, if emesis has not occurred, vomiting may be induced with ipecac syrup. {01} In an unconscious patient, a clear airway must be secured and ventilatory support may be required. {18} Gastric lavage may be performed followed by administration of a suspension of activated charcoal that is to be left in the stomach. {01} {02}

To enhance elimination: A saline cathartic will hasten the gastrointestinal passage of the gum. {01}



For transdermal systems only:
To decrease absorption: Remove the patch and flush the skin surface with water and dry. Do not use soap because it may increase nicotine absorption. {05} {06} {07} {20} {25} {27} {28} {29} If the patch has been ingested, administer activated charcoal. {06} {07} {20} {25} {27} {29} In an unconscious patient, the airway should be secured before administering activated charcoal via a nasogastric tube. Repeated doses of charcoal should be administered as long as the patch remains in the gastrointestinal tract because it will continue to release nicotine. {05} {06} {07} {20} {25} {27} {29}

To enhance elimination: A saline cathartic or sorbitol may be added to the first dose of activated charcoal to speed passage of the patch. {06} {07} {20} {25} {27} {29}



For all nicotine replacement products:
Supportive care: Administration of anticonvulsants such as lorazepam {40} or barbiturates for seizures, {05} {06} {07} {08} {20} {25} {27} {29} and atropine for excessive bronchial secretions or diarrhea; {05} {06} {07} {08} {20} {25} {27} {28} {29} respiratory support for respiratory failure; {01} {05} {06} {07} {08} {20} {25} {27} {28} {29} intensive fluid support for hypotension and cardiovascular collapse. {01} {05} {06} {07} {08} {20} {25} {27} {28} {29} Vasopressors may be administered if hypotension does not respond to atropine and fluids. {40} Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Nicotine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to nicotine or to any component of the product

Pregnancy—Not recommended during pregnancy; spontaneous abortions have been reported; use only if the likelihood of smoking cessation outweighs the potential risks that continued smoking poses to the fetus





Breast-feeding—Distributed into and accumulates in breast milk





Use in children—Small amounts of nicotine can cause serious harm in children






Dental—Chewing gum may cause severe occlusive stress resulting in damage to teeth, dentures, or dental work
Other medications, especially alpha-adrenergic blocking agents, insulin, propoxyphene, propranolol, sympathomimetic agents, or xanthine-derivative bronchodilators (except dyphylline)
Other medical problems, especially severe angina pectoris, life-threatening cardiac arrhythmias, recent cerebrovascular accident, hypertension, or post–myocardial infarction state

Proper use of this medication

Proper administration of the chewing gum
» Reading patient instructions carefully before using

» Using as directed on the label; participating in a behavioral modification program to increase likelihood of success in quitting {55}

» Using gum only when there is an urge to smoke; chewing gum slowly and intermittently (chewing it several times, then “parking” it between cheek and gums; chewing again after tingling sensation subsides) {55} for 30 minutes

» Not chewing too fast, not chewing more than one piece of gum at a time, and not chewing more than one piece within an hour, {55} to avoid adverse effects or overdose

» Not drinking acidic beverages, such as citrus juices, coffee, soft drinks, or tea within 15 minutes before or while chewing gum

Compliance with chewing gum therapy
» Reducing number of pieces chewed each day over a 2- to 3-month period

» Importance of carrying gum at all times during therapy

Using hard sugarless candy between doses of gum to help alleviate urge to smoke between doses of chewing gum {55}

Proper administration of the transdermal systems
» Reading patient instructions carefully before using

» Participating in a behavioral modification program to increase likelihood of success in quitting {55}

» Keeping patch in sealed pouch until ready to apply to skin

» Not trimming or cutting patch

Applying to clean, dry skin area on upper arm or torso free of oil, hair, scars, cuts, burns, or irritation

Pressing the patch firmly in place with palm for about 10 seconds; making sure there is good contact, especially around edges

Keeping patch in place even during showering, bathing, or swimming; replacing patches that have fallen off

» Washing hands with plain water after handling patches; soap will enhance transdermal absorption of nicotine

» Alternating application sites; not keeping patch on for more than 24 hours because it loses strength and may irritate the skin

Folding used patches in half with adhesive sides together, and replacing in protective pouch or aluminum foil; disposing of patch carefully, out of reach of children or pets

Getting into the habit of changing patch at the same time each day to help increase compliance

Removing the patch during strenuous exercise to prevent increased nicotine plasma concentrations

Removing the 24-hour patch at bedtime (after 16 hours) if you begin having abnormal dreams or disturbed sleep and putting a new patch on upon awakening the next day {22}

» Proper dosing

» Proper storage

Precautions while using this medication
» Not smoking during treatment with nicotine replacement products {17}

» Not using nicotine replacement products during pregnancy

» Preventing accidental ingestion of nicotine replacement products by children or pets to avoid poisoning

For the chewing gum only
» Not chewing more than 24 pieces of gum a day

» Not using gum for longer than 6 months to avoid physical dependence; consulting physician if need for gum continues after 6 months {55}

» Discontinuing use and consulting physician or dentist if excessive sticking to dental work occurs; gum may damage dental work or dentures

For the transdermal systems only
» Calling physician and not applying new patch if evidence of allergic reaction; knowing that allergic reaction to nicotine patch could cause reaction to use of cigarettes or other products containing nicotine

» Not using patches for longer than 12 weeks; consulting physician if need for patch continues after 12 weeks {55}


Side/adverse effects
Signs of potential side effects, especially injury or irritation to mouth, teeth, or dental work (with gum only); hypertension; fast or irregular heartbeat; and hypersensitivity reactions


General Dosing Information
The necessity of immediate cessation of smoking upon initiation of therapy must be emphasized. {01} {06} {07} {08} {17} {20} {22} {25} {26} {27} {28} {29} Continued smoking while using nicotine replacement products may cause adverse effects as a result of peak nicotine concentrations higher than those found after smoking alone. {06} {07} {20} {25} {27} {28} {29}



For chewing gum only
When there is an urge to smoke, one piece of gum is chewed very slowly and intermittently (chewing it several times, then “parking” it between the cheek and gums; chewing again after the tingling sensation subsides) for about 30 minutes until most of the nicotine is released. {01}

The amount of nicotine released depends on the rate of chewing and the amount of time the saliva is in contact with the resin.

No liquids, especially acidic beverages, should be consumed within 15 minutes before or while chewing a piece of gum {17} {18} {19} because a decrease in the pH of the mouth may interfere with the absorption of nicotine. {18} {19}

The use of nicotine polacrilex for longer than 6 {55} months may be an indication that this medication is being used as a substitute source of nicotine to maintain nicotine dependence. However, while the use of nicotine replacement products is preferable to a return to smoking, {56} these products should be continued beyond 6 months only if the patient believes that discontinuation of replacement therapy will definitely result in an immediate resumption of smoking. {55} {01}

For transdermal systems only
If a patient is unable to stop smoking by the fourth week of therapy, treatment should be discontinued, as the patient is unlikely to quit on that attempt. {05} {06} {07} {08} {25} {27} {28} {29}

It is recommended that nicotine transdermal systems be removed during, {28} and a new system applied following, {52} strenuous exercise. If left on, nicotine plasma concentrations may be increased as a result of increased absorption of nicotine from the skin depot, increased skin temperature, and increased cutaneous vasodilation and perfusion. {53} {54}

The use of nicotine transdermal systems for longer than 12 weeks in patients who have stopped smoking has not been evaluated and is not recommended. {05} {06} {07} {08} {25} {27} {28} {29}

Most manufacturers supply supportive instructional materials and provide telephone information accessible by patients.


Oral Dosage Forms

NICOTINE POLACRILEX GUM{16} USP

Usual adult and adolescent dose
Smoking cessation adjunct
Patients smoking fewer than twenty-five cigarettes a day, use the 2-mg strength. {17}

Patients smoking twenty-five or more cigarettes a day, use the 4-mg strength. {17}

Weeks one to six—Oral, one piece of chewing gum every one to two hours. {17}

Weeks seven to nine—Oral, one piece of chewing gum every two to four hours. {17}

Weeks ten to twelve—Oral, one piece of chewing gum every four to eight hours. {17}

Note: Patients should use at least nine pieces of chewing gum daily during the first six weeks of therapy. {17} {55}



Usual adult prescribing limits
Twenty-four pieces of chewing gum a day. {17} {21}

Usual pediatric dose
Safety and efficacy have not been established. {01}

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—


2 mg (OTC) [Nicorette (flavors) (glycerin) (gum base) (sodium bicarbonate) (sodium carbonate) (sorbitol){17}]


4 mg (OTC) [Nicorette (flavors) (glycerin) (gum base) (sodium carbonate) (sorbitol) (D&C Yellow No. 10){17}]

Canada—


2 mg (OTC) [Nicorette (gum) (menthol) (magnesium oxide) (peppermint oil) (sodium bicarbonate) (sodium carbonate) (xylitol){18}]


4 mg (Rx) [Nicorette Plus (gum) (magnesium oxide) (menthol) (peppermint oil) (sodium carbonate) (xylitol) (D&C Yellow No. 10){19}]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), {55} unless otherwise specified by manufacturer. Protect from light. {18} {19}

Auxiliary labeling:
   • Chew slowly.
   • Do not chew more than 24 {17} {21} pieces in one day.



Topical Dosage Forms

NICOTINE TRANSDERMAL SYSTEM{24} USP

Usual adult and adolescent dose
Smoking cessation adjunct; depending on the product


Patients weighing more than 100 pounds (45 kg), smoking more than ten cigarettes a day, and without cardiovascular disease:


Sixteen-hour system: Topical, to intact skin—
Nicotrol: One 15-mg system applied for sixteen hours per day for six weeks. {26} Alternatively, one 15-mg system applied for sixteen hours per day for eight weeks. Patients who have successfully abstained from smoking for eight weeks should have their dose reduced to one 10-mg system applied for sixteen hours per day for two weeks. The dosage should be further reduced to one 5-mg system applied for sixteen hours per day for two weeks. {29}



Twenty-four-hour system: Topical, to intact skin—
Habitrol: Initially one 21-mg system per day for three {28} to eight weeks. {06} {28} Patients who have successfully abstained from smoking should have their dose reduced to one 14-mg system per day for the next two to four weeks. {06} The dosage should be further reduced to one 7-mg system per day for the following two to four weeks. {06}

Nicoderm, NicoDerm CQ, or generic: Initially one 21-mg system per day for six weeks. {22} {25} {27} Patients who have successfully abstained from smoking should have their dose reduced to one 14-mg system per day for two weeks. The dosage should be further reduced to one 7-mg system per day for two weeks. {05} {22} {25} {27}

Prostep: Initially one 22-mg system per day for four to eight weeks. {07} {08} Patients who have successfully abstained from smoking should have their dose reduced to one 11-mg system per day for two to four weeks. {07} {08}




Patients weighing less than 100 pounds (45 kg), smoking fewer than ten cigarettes a day, or with cardiovascular disease:


Sixteen-hour system: Topical, to intact skin—
Nicotrol: One 15-mg system applied for sixteen hours per day for six weeks. {26}



Twenty-four-hour system: Topical, to intact skin—
Habitrol: Initially one 14-mg system per day for four to eight weeks. {06} Patients who have successfully abstained from smoking should have their dose reduced to one 7-mg system per day for the next two to four weeks. {06}

Nicoderm, NicoDerm CQ, or generic: Initially one 14-mg system per day for six weeks. {05} {22} {25} {27} Patients who have successfully abstained from smoking should have their dose reduced to one 7-mg system per day for two {22} {27} to four weeks. {25} {27}

Prostep: One 11-mg system per day for four to eight weeks. {07} {08}




Usual pediatric dose
Safety and efficacy have not been established. {05} {06} {07} {08} {25}

Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—



16-hour System


15 mg (OTC) [Nicotrol{26}]



24-hour Systems


7 mg (Rx) [Habitrol{06}][Generic]{25}


7 mg (OTC) [NicoDerm CQ{22}]


11 mg (Rx) [Prostep{07}]


14 mg (Rx) [Habitrol{06}][Generic]{25}


14 mg (OTC) [NicoDerm CQ{22}]


21 mg (Rx) [Habitrol{06}][Generic]{25}


21 mg (OTC) [NicoDerm CQ{22}]


22 mg (Rx) [Prostep{22}]

Canada—



16-hour Systems


5 mg (Rx) [Nicotrol{29}]


10 mg (Rx) [Nicotrol{29}]


15 mg (Rx) [Nicotrol{29}]



24-hour Systems


7 mg (Rx) [Nicoderm{27}]


7 mg (OTC) [Habitrol]{31}


11 mg (Rx) [Prostep{20}{51}]


14 mg (Rx) [Nicoderm{27}]


14 mg (OTC) [Habitrol]{31}


21 mg (Rx) [Nicoderm{27}]


21 mg (OTC) [Habitrol]{31}


22 mg (Rx) [Prostep{20}{51}]

Note: Nicotine transdermal systems are designed to release a constant, controlled dose of nicotine over the period during which they are applied to the skin. Systems are labeled by the dose actually absorbed by the patient, not by the total nicotine content. {25}


Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in the intact, {05} {06} {07} {08} {25} {27} {28} {29} light-resistant {24} pouch. Because nicotine is volatile, the system may lose strength if removed from pouch prematurely. {05} {06} {07} {08} {25}

Auxiliary labeling:
   • For external use only.
   • Follow the manufacturer's directions carefully.



Revised: 01/29/1999



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