Nicotine Tartrate

(USAN)

💊 Chemical information

Nicotine Bitartrate (USAN).
Chemical formula: C10H14N2,2C4H6O6,2H2O = 498.4.
CAS — 65-31-6 (anhydrous nicotine tartrate).
ATC — N07B A01.
ATC Vet — QN07BA01.

💊 Dependence and Withdrawal

Nicotine dependence is most commonly associated with cigarette smoking. It is characterised by a strong desire to continue taking the agent, a physical and psychological need for it, and a characteristic abstinence syndrome on withdrawal. Common symptoms seen on nicotine withdrawal include irritability, anxiety, depression, restlessness, poor concentration, increased appetite, weight gain, and insomnia. The management of smoking cessation is discussed under Uses and Administration, below. Mild withdrawal symptoms have been reported from nicotine replacement preparations used to aid smoking cessation.
1. Hatsukami D, et al. Physical dependence on nicotine gum: effect of duration of use. Psychopharmacology (Berl) 1993; 111: 449–56
2. Benowitz NL, Henningfield JE. Establishing a nicotine threshold for addiction: the implications for tobacco regulation. N Engl J Med 1994; 331: 123–5
3. Keenan RM, et al. Pharmacodynamic effects of cotinine in abstinent cigarette smokers. Clin Pharmacol Ther 1994; 55: 581–90
4. Slade J, et al. Nicotine and addiction: the Brown and Williamson documents. JAMA 1995; 274: 225–33
5. Kessler DA. Nicotine addiction in young people. N Engl J Med 1995; 333: 186–9
6. Doll R, Crofton J, eds. Tobacco and health. Br Med Bull 1996; 52: 1–223
7. Benowitz NL. Nicotine addiction. Prim Care 1999; 26: 611–31
8. Colby SM, et al. Are adolescent smokers dependent on nicotine? A review of the evidence. Drug Alcohol Depend 2000; 59 (suppl 1): S83–S95
9. Royal College of Physicians. Nicotine addiction in Britain: a report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians, 2000. Also available at: http://www.rcplondon.ac.uk/pubs/books/nicotine/ index.htm (accessed 30/07/08
10. West R, et al. A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl) 2000; 149: 198–202.

💊 Adverse Effects and Treatment

Nicotine is a highly toxic substance and in acute poisoning death may occur within 1 hour due to respiratory failure arising from paralysis of the muscles of respiration. The fatal oral dose of nicotine for an adult is from 40 to 60 mg. Less severe poisoning causes initial stimulation followed by depression of the autonomic nervous system. Typical symptoms include burning of the mouth and throat, nausea and salivation, abdominal pain, vomiting, diarrhoea, dizziness, weakness, hypertension followed by hypotension, mental confusion, headache, hearing and visual disturbances, dyspnoea, faintness, convulsions, sweating, and prostration. Transient cardiac standstill or paroxysmal atrial fibrillation may occur. Nicotine is rapidly absorbed through the skin or by inhalation as well as by ingestion, and nicotine poisoning may occur due to careless handling when it is used as a horticultural insecticide. Prompt treatment of nicotine poisoning is essential. If contact was with the skin, contaminated clothing should be removed and the skin washed thoroughly with cold water without rubbing. If the patient has swallowed nicotine, gastric lavage and activated charcoal may be beneficial. Treatment is supportive and includes support of respiration and control of convulsions. Atropine may be used to suppress features of parasympathomimetic stimulation. Apart from effects such as dizziness, headache, and gastrointestinal disturbances mentioned above, adverse effects associated with nicotine replacement preparations have also included cold and flu-like symptoms, palpitations, insomnia, vivid dreams, myalgia, chest pain, blood pressure changes, anxiety, irritability, somnolence, and dysmenorrhoea. Allergic reactions have been reported. Adverse effects associated with specific preparations include skin reactions with transdermal patches; nasal irritation, epistaxis, lachrymation, and sensations in the ear with the nasal spray; throat irritation with the spray, inhalator, sublingual tablets, lozenges, or chewing gum; aphthous ulceration with the inhalator, sublingual tablets, lozenges, or chewing gum; increased salivation and sometimes swelling of the tongue with chewing gum; cough, rhinitis, stomatitis, sinusitis, and dry mouth with the inhalator; and unpleasant taste with the sublingual tablets or lozenges. Excessive swallowing of nicotine released from oral replacement preparations may cause hiccups in the first few days of treatment.
1. Greenland S, et al. A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Safety 1998; 18: 297–308
2. Gourlay SG, et al. Predictors and timing of adverse experiences during transdermal nicotine therapy. Drug Safety 1999; 20: 545–55.

💊 Pharmacokinetics

Nicotine is readily absorbed through mucous membranes and the skin; bioavailability of oral nicotine is low due to extensive firstpass metabolism. Nicotine is widely distributed; it crosses the blood-brain barrier and the placenta and is found in breast milk. The elimination half-life is about 1 to 2 hours. Nicotine is metabolised mainly in the liver via the cytochrome P450 isoenzyme CYP2A6 to cotinine and nicotine-N-oxide. Nicotine and its metabolites are excreted in the urine.
1. Gorsline J, et al. Steady-state pharmacokinetics and dose relationship of nicotine delivered from Nicoderm (nicotine transdermal system). J Clin Pharmacol 1993; 33: 161–8
2. Gupta SK, et al. Bioavailability and absorption kinetics of nicotine following application of a transdermal system. Br J Clin Pharmacol 1993; 36: 221–7
3. Schneider NG, et al. Clinical pharmacokinetics of nasal nicotine delivery: a review and comparison to other nicotine systems. Clin Pharmacokinet 1996; 31: 65–80
4. Benowitz NL, et al. Sources of variability in nicotine and cotinine levels with the use of nicotine nasal spray, transdermal nicotine and cigarette smoking. Br J Clin Pharmacol 1997; 43: 259–67
5. Zins BJ, et al. Pharmacokinetics of nicotine tartrate after singledose liquid enema, oral, and intravenous administration. J Clin Pharmacol 1997; 37: 426–36
6. Schneider NG, et al. The nicotine inhaler: clinical pharmacokinetics and comparison with other nicotine treatments. Clin Pharmacokinet 2001; 40: 661–84.

💊 Uses and Administration

The main physiological action of nicotine is paralysis of all autonomic ganglia, preceded by stimulation. Centrally, small doses cause respiratory stimulation, while larger doses produce convulsions and arrest of respiration. The effects on skeletal muscle are similar to those on ganglia. Nicotine chewing gum, transdermal patches, lozenges, sublingual tablets, nasal spray, or inhalator are used as aids for smoking cessation (below) and many such products are also used to reduce the amount smoked. For smoking cessation, treatment is usually continued for up to 3 months, then gradually withdrawn. For smoking reduction, it may be continued for up to 6 months, and an attempt to quit then made. If use is to be continued beyond 9 months, additional advice from a healthcare professional should be sought.
Chewing gum is available in strengths of 2 mg and 4 mg; the nicotine may be present in the gum in the form of a complex with methacrylic acid polymer (nicotine polacrilex). Individuals who smoke 20 cigarettes or less per day should start with the 2-mg strength gum chewed slowly over about 30 minutes when the urge to smoke occurs. Those who smoke over 20 cigarettes a day or require more than 15 pieces daily of the 2-mg gum should receive the 4-mg strength. Not more than 15 pieces should be used per day.
Sublingual tablets containing the equivalent of 2 mg of nicotine as a β-cyclodextrin complex may be used: the recommended dose is 1 or 2 tablets sublingually every hour, increased to a maximum of 40 tablets daily if necessary.
Lozenges containing 1 or 2 mg of nicotine (as the polacrilex or as the tartrate) are available. The initial dose is 1 lozenge every 1 to 2 hours increased to a maximum daily dose of 30 of the 1-mg lozenges or 15 of the 2-mg lozenges.
Adhesive transdermal patches are designed to be worn for 16 or 24 hours and are available in different strengths that deliver from 5 to 21 mg during the recommended wearing time. One patch should be applied daily, on waking, to a dry, non-hairy area of skin on the hip, trunk, or upper arm, usually beginning with the highest strength or with a dose determined by the previous daily consumption of cigarettes. A different site of application should be used each day with several days elapsing before the patch is applied to the same area of skin.
A suggested initial dosage for a nasal spray containing 500 micrograms per spray is one spray administered into each nostril up to twice hourly as required up to a maximum of 80 sprays daily for the first 8 weeks and reduced gradually thereafter. Treatment for more than 3 months is not recommended.
Nicotine inhalator cartridges contain nicotine 10 mg for use in an appropriate inhaler mouthpiece. The initial dose is 6 to 16 cartridges daily for up to 12 weeks and is reduced gradually over a further 4 to 12 weeks. Nicotine has been used as a horticultural insecticide.

Alzheimer’s disease.

The use of nicotine as a cholinergic agonist is one of a number of methods being studied1 to overcome brain cholinergic deficits in patients with Alzheimer’s disease. Preliminary studies2,3 using nicotine patches have been of limited duration and were inconclusive. Transdermal nicotine has been used for the control of behavioural symptoms such as agitation in a small number of patients with

Alzheimer’s disease.

4 A systematic review5 was unable to present any conclusions on the efficacy and safety of nicotine in Alzheimer’s disease because of a lack of adequate randomised controlled studies.
1. Baldinger SL, Schroeder DJ. Nicotine therapy in patients with Alzheimer’s disease. Ann Pharmacother 1995; 29: 314–15
2. Wilson AL, et al. Nicotine patches in Alzheimer’s disease: pilot study on learning, memory, and safety. Pharmacol Biochem Behav 1995; 51: 509–14
3. Snaedal J, et al. The effects of nicotine in dermal plaster on cognitive functions in patients with Alzheimer’s disease. Dementia 1996; 7: 47–52
4. Rosin RA, et al. Transdermal nicotine for agitation in dementia. Am J Geriatr Psychiatry 2001; 9: 443–4
5. López-Arrieta JLA, Sanz FJ. Nicotine for Alzheimer’s disease. Available in The Cochrane Database of Systematic Reviews; Issu
2. Chichester: John Wiley; 2001 (accessed 28/04/05).

Blepharospasm.

Nicotine nasal spray was reported to be of benefit in a patient with blepharospasm refractory to botulinum A toxin.1 However, a subsequent study in 4 patients with blepharospasm reported no improvement with the use of nicotine nasal spray.2
1. Dursun SM, et al. Treatment of blepharospasm with nicotine nasal spray. Lancet 1996; 348: 60
2. Dressler D, et al. Nicotine nasal spray is not reliable treatment for blepharospasm: results of a pilot study. Mov Disord 1998; 13: 190.

Extrapyramidal disorders.

Nicotine transdermal patches have been reported to produce beneficial effects1 in schizophrenic patients with antipsychotic-induced akathisia. Because of an apparent inverse association between smoking and Parkinson’s disease, transdermal nicotine patches have been investigated in the treatment of parkinsonian symptoms, but with little evidence of overall benefit.2,3
1. Anfang MK, Pope HG. Treatment of neuroleptic-induced akathisia with nicotine patches. Psychopharmacology (Berl) 1997; 134: 153–6
2. Vieregge A, et al. Transdermal nicotine in PD: a randomized, double-blind, placebo-controlled study. Neurology 2001; 57: 1032–5
3. Lemay S, et al. Lack of efficacy of a nicotine transdermal treatment on motor and cognitive deficits in Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 31–9.

Skin disorders.

There have been anecdotal reports of nicotine producing beneficial effects in various skin disorders, including pyoderma gangrenosum,1 and dermatitis due to fluorouracil therapy.2
1. Kanekura T, et al. Nicotine for pyoderma gangrenosum. Lancet 1995; 345: 1058
2. Kingsley EC. 5-Fluorouracil dermatitis prophylaxis with a nicotine patch. Ann Intern Med 1994; 120: 813.

Smoking cessation.

Smoking is the single most important cause of preventable illness and premature death in the UK and USA; it is estimated that around 1 in 5 deaths are due to smokingrelated illnesses. The financial burden of smoking-related diseases on healthcare providers is also substantial. Many governments have undertaken initiatives to promote smoking cessation for which there is substantial evidence of a decline in the risk of disease1 and death.2 As the abstinence period increases, the reduced risk of disease in former smokers may even approach, although rarely does it ever equal, that of people who have never smoked.1. Nicotine dependence and the development of a characteristic withdrawal syndrome (see Dependence and Withdrawal, above) make stopping smoking very difficult. Many individuals relapse when trying to give up or need several attempts before successfully stopping. Both nonpharmacological and pharmacological treatments can improve the abstinence rate and are most effective when the two approaches are combined.3-12 Nonpharmacological methods include counselling, training in coping skills, and support groups; although the abstinence rate increases with the intensity of the support, even brief advice is effective in encouraging cessation. The first-line pharmacological intervention is nicotine replacement therapy (NRT) which is an effective treatment for reducing the cravings associated with stopping smoking. NRT is available in numerous formulations: chewing gum, transdermal patches, inhalators, nasal sprays, sublingual tablets, and lozenges. A systematic review10 of NRT found abstinence was more than doubled when compared with controls, regardless of the intensity of any additional nonpharmacological support. Choice of formulation is based on patient preference, tolerance, and previous treatments, if any. The transdermal patch is easiest to use and compliance is greatest with this route but local effects may be troublesome. The gum has an unpleasant taste initially and some find the chewing action difficult. The sublingual tablet may be useful for those who have difficulty chewing the gum. The nasal spray has a fast onset of action but may cause local irritation. The inhalator has the advantage of simulating cigarette smoking but may cause local irritation of the mouth and throat. The lozenge has the advantage that it can be sucked discreetly. Patients who are unable to tolerate one type of NRT may benefit from a course of an alternative NRT preparation. Combination therapy with different types of NRT (patches with either the nasal spray, inhalator, or chewing gum) has also been tried as a means of increasing efficacy. NRT for smoking cessation is usually continued for about 3 months before being withdrawn. Although the manufacturers advise gradual withdrawal, others6,8 have found that this offers no advantage and recommend abrupt withdrawal. NRT for smoking reduction is typically continued for longer periods. NRT has also been used long-term and may be of particular benefit in those patients who feel they would relapse if NRT was stopped or in those who have persistent withdrawal symptoms. There has been concern over the use of NRT in patients with cardiovascular disease (see Effects on the Cardiovascular System, above) but clinical experience and studies have shown that NRT can be used with caution in these patients. The use of NRT in those who have suffered a recent myocardial infarction or those with severe arrhythmias or unstable angina is, however, contraindicated as such patients have not been adequately studied. A number of other drugs have also been used to achieve abstinence from smoking.13-15 Bupropion is effective and recommended by some as a first-line alternative to NRT; its action is said to be independent of its antidepressant activity. Bupropion in combination with NRT has been used successfully. Evidence to support the use of most other antidepressants is lacking,16 but nortriptyline appears to be effective and is used as a second-line drug. A study17 found, however, that there was no advantage in combining nortriptyline with NRT. Clonidine is also effective but adverse effects limit its usefulness.15 Preliminary investigations suggest that selegiline and mecamylamine may be effective.13,15 The cannabinoid-1 receptor antagonist rimonabant has produced promising results in early studies,13,14 although a systematic review18 of 3 randomised controlled studies found the evidence to be inconclusive. A systematic review19 of studies on the use of the oral nicotine receptor partial agonists varenicline and cytisine concluded that both drugs have a potential place in smoking cessation. Varenicline compared favourably with placebo and bupropion in helping smokers to quit, but its efficacy in preventing relapse still remains to be fully established. Like bupropion, varenicline is recommended by some as a first-line alternative to NRT. Cytisine is widely used in central and eastern Europe but the current evidence for efficacy is limited and better designed studies are required to test earlier findings. There is little or no evidence to support the efficacy of other treatments such as silver acetate, lobeline, or anxiolytics such as buspirone, and their use is not recommended. A vaccine for the prevention of smoking relapse is under investigation.13,14
1. Dresler CM, et al. Reversal of risk upon quitting smoking. Lancet 2006; 368: 348–9
2. Vollset SE, et al. Smoking and deaths between 40 and 70 years of age in women and men. Ann Intern Med 2006; 144: 381–9
3. American Society of Health-System Pharmacists. ASHP therapeutic position statement on smoking cessation. Am J HealthSyst Pharm 1999; 56: 460–4
4. Anonymous. Nicotine replacement to aid smoking cessation. Drug Ther Bull 1999; 37: 52–4
5. West R, et al. Smoking cessation guidelines for health professionals: an update. Thorax 2000; 55: 987–99
6. Royal College of Physicians. Nicotine addiction in Britain: a report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians, 2000. Also available at: http://www.rcplondon.ac.uk/pubs/books/nicotine/ index.htm (accessed 02/07/04
7. Fiore MC, et al. A clinical practice guideline for treating tobacco use and dependence: a US public health service report. JAMA 2000; 283: 3244–54
8. Simpson D. Smoking cessation. In: Doctors and tobacco: medicine’s big challenge. London: Tobacco Control Resource Centre, British Medical Association, 2000. Also available at: http:// www.bma.org.uk/tcrc.nsf/4723e4b3bbc9362e802566e300360f8e/ d51b23fb23791f22802568ab00668cf1/06.00FILE/D&T_EN.pdf (accessed 14/07/06
9. Covey LS, et al. Advances in non-nicotine pharmacotherapy for smoking cessation. Drugs 2000; 59: 17–31
10. Stead LF, et al. Nicotine replacement therapy for smoking cessation. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2008 (accessed 09/07/08)
11. Nides M. Update on pharmacologic options for smoking cessation treatment. Am J Med 2008; 121 (suppl 1): S20–S31
12. Ranney L, et al. Systematic review: smoking cessation intervention strategies for adults and adults in special populations. Ann Intern Med 2006; 145: 845–56
13. Foulds J, et al. Developments in pharmacotherapy for tobacco dependence: past, present and future. Drug Alcohol Rev 2006; 25: 59–71
14. Garwood CL, Potts LA. Emerging pharmacotherapies for smoking cessation. Am J Health-Syst Pharm 2007; 64: 1693–8. Correction. ibid.; 1995
15. Buchhalter AR, et al. Novel pharmacological approaches for treating tobacco dependence and withdrawal: current status. Drugs 2008; 68: 1067–88
16. Hughes JR, et al. Antidepressants for smoking cessation. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2007 (accessed 09/07/08)
17. Aveyard P, et al. Nortriptyline plus nicotine replacement versus placebo plus nicotine replacement for smoking cessation: pragmatic randomised controlled trial. BMJ 2008; 336: 1223–7
18. Cahill K, Ussher M. Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2007 (accessed 09/07/08)
19. Cahill K, et al. Nicotine receptor partial agonists for smoking cessation. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2007 (accessed 28/06/07).

Spasticity.

There have been anecdotal reports1 of beneficial responses to nicotine in spastic dystonia.
1. Vaughan CJ, et al. Treatment of spastic dystonia with transdermal nicotine. Lancet 1997; 350: 565.

Tics.

Tourette’s syndrome is characterised by motor and vocal tics and behavioural disturbances. Nicotine1-5has been reported to be of benefit when used alone or with the more usual treatment of haloperidol in patients with Tourette’s syndrome whose symptoms were not satisfactorily controlled with haloperidol alone. It is hoped that the use of transdermal nicotine patches will avoid the reported problems of compliance associated with the taste and gastrointestinal effects of nicotine gum.
1. McConville BJ, et al. The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency to Tourette’s disorder. Biol Psychiatry 1992; 31: 832–40
2. Silver AA, Sanberg PR. Transdermal nicotine patch and potentiation of haloperidol in Tourette’s syndrome. Lancet 1993; 342: 182
3. Dursun SM, et al. Longlasting improvement of Tourette’s syndrome with transdermal nicotine. Lancet 1994; 344: 1577
4. Sanberg PR, et al. Nicotine for the treatment of Tourette’s syndrome. Pharmacol Ther 1997; 74: 21–5
5. Silver AA, et al. Transdermal nicotine and haloperidol in Tourette’s disorder: a double-blind placebo-controlled study. J Clin Psychiatry 2001; 62: 707–14.

Ulcerative colitis.

Investigation of the use of nicotine in ulcerative colitis has been prompted by the observation that this condition is rare in smokers.1 A systematic review2 found that transdermal nicotine was more effective than placebo in producing remission in patients with active ulcerative colitis, but appeared to be no more effective than standard therapy with a corticosteroid or aminosalicylate, and was associated with more adverse effects. It appears to be ineffective in maintaining disease remission.3 Any role is likely to be limited to patients who do not respond to standard therapy and who can tolerate the adverse effects.2 Local delivery to the colon, in the form of enemas4-6 and oral modified-release capsules,7 is under investigation as a means of reducing the adverse effects of nicotine.
1. Guslandi M. Nicotine treatment for ulcerative colitis. Br J Clin Pharmacol 1999; 48: 481–4
2. McGrath J, et al. Transdermal nicotine for induction of remission in ulcerative colitis. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2004 (accessed 08/03/06)
3. Thomas GAO, et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med 1995; 332: 988–92
4. Sandborn WJ, et al. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther 1997; 11: 663–71
5. Ingram JR, et al. Nicotine enemas for treatment of ulcerative colitis: a study of the pharmacokinetics and adverse events associated with three doses of nicotine. Aliment Pharmacol Ther 2004; 20: 859–65
6. Ingram JR, et al. A randomized trial of nicotine enemas for active ulcerative colitis. Clin Gastroenterol Hepatol 2005; 3: 1107–14
7. Green JT, et al. An oral formulation of nicotine for release and absorption in the colon: its development and pharmacokinetics. Br J Clin Pharmacol 1999; 48: 485–93.

💊 Preparations

USP 31: Nicotine Polacrilex Gum; Nicotine Transdermal System.

Proprietary Preparations

Arg.: Nicorette; Nicotinell TTS; Austral.: Nicabate; Nicorette; Nicotinell; QuitX; Austria: Nicorette; Nicotinell; Nicotrol; Belg.: Nicorette; Nicotinell; NiQuitin; Braz.: Nicorette; Nicotinell TTS; NiQuitin; Canad.: Habitrol; Nicoderm; Nicorette; Nicotrol; Prostep; Chile: Nicorette; Nicotinell; Cz.: Nicopass; Nicopatch; Nicorette; Nicotinell; NiQuitin; Denm.: Nicorette; Nicotinell; NiQuitin†; Fin.: Nicorette; Nicotinell; Fr.: Nicogum; Nicopass; Nicopatch; Nicorette; Nicotinell; NiQuitin; Ger.: Nicorette; Nicotinell; nikofrenon; NiQuitin; Gr.: Nicopass; Nicorette; Nicotinell; Hong Kong: Nicorette; Nicotinell; Hung.: Nicopass; Nicorette; Nicotinell; NiQuitin; India: Nicotinell TTS†; Irl.: Nicorette; Nicotinell; NiQuitin; Israel: Nicorette; Nicotinell; NiQuitin; Ital.: Nicorette; Nicotinell; NiQuitin; Malaysia: Nicorette; Nicotinell; Mex.: Nicorette; Nicotinell TTS†; NiQuitin; Neth.: Nicorette; Nicotinell; NiQuitin; Norw.: Nicorette; Nicotinell; NZ: Habitrol; Nicabate; Nicorette; Nicotinell; Nicotrol; Pol.: Nicorette; Nicotinell; NiQuitin; Port.: Nicopass; Nicopatch; Nicorette; Nicotinell TTS; NiQuitin; Rus.: Nicorette (Никоретте); S.Afr.: Nicorette; Quit; Singapore: Nicorette; Nicotinell; Spain: Nicomax; Nicorette; Nicotinell; Nicotrol†; NiQuitin; Swed.: Nicorette; Nicotinell; Nikotugg; NiQuitin; Switz.: Nicorette; Nicotinell; Thai.: Nicorette; Nicotinell; Turk.: Nicotinell; UK: Nicopass; Nicopatch; Nicorette; Nicotinell; NiQuitin; USA: Commit; Habitrol; Nicoderm; Nicorette; Nicotrol; Prostep; Venez.: Nicorette†.
Published May 08, 2019.