Nicotine

Registered South African indications:

• Temporary aid to the cigarette smoker seeking to give up their smoking habit while participating in a behavioural modification programme under professional supervision (Efficacy, without concomitant participation in a behavioural modification programme has not been established)

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy women or women who may become pregnant
• Safety and effectiveness in children and adolescents who smoke have not been evaluated. Should not be given to children
• Immediate post-myocardial infarction period
• Life-threatening dysrhythmias
• Severe or worsening angina pectoris
• Active temporomandibular joint disease

Caution recommended in the following patient groups

• Breastfeeding
• Severe renal impairment
• Moderate to severe hepatic impairment

Cardiovascular and cerebrovascular disease

• Use with caution and evaluate benefits against risks in patients with coronary heart disease, serious arrhythmias, vasospastic diseases, recent stroke, or uncontrolled hypertension
• Non-pharmacological interventions, such as counselling should be considered

Endocrine disorders

• Use with caution in patients with hyperthyroidism or phaeochromocytoma as nicotine-induced catecholamine release remains unaffected by tolerance

Diabetes mellitus

• Close monitoring of blood sugar levels is required during initiation as changes in catecholamine release can affect carbohydrate metabolism

Renal and hepatic impairment

• Use with caution in patients with moderate to severe hepatic impairment or severe renal impairment due to decreased clearance of nicotine and its metabolites

Gastrointestinal disorders

• Nicotine may exacerbate symptoms in patients with esophagitis, gastric ulcers, or active/inactive peptic ulcer disease

Rapid administration

• Chewing the gum too fast can cause light-headedness, nausea, hiccups, and mouth irritation; ensure the gum is chewed slowly to control these effects
• Patients should not exceed the recommended dosage

Smoking urges

• As the urge to smoke fades, gradually reduce the number of pieces of gum chewed each day. Unless advised otherwise, no attempt to stop using the gum should be made until the craving is satisfied with one or two pieces a day
• The gum should not be used for more than 3 months
• Patients should remember to carry the gum with them at all times in case they feel the sudden urge to smoke again

History of seizures

• Exercise caution in patients with a history of epilepsy or seizures when introducing nicotine replacement therapy

Denture wearers

• Nicotine gum may be difficult to chew and can occasionally stick to or damage dentures

Pediatric population

• Do not administer to children; nicotine doses tolerated by adults can cause fatal toxicity in paediatric patients

Excessive consumption (Xylitol)

• Formulations containing xylitol may cause diarrhoea and flatulence if ingested in large amounts

Duration of use

• Do not use for more than 3 months; usage should be gradually reduced as cravings fade to avoid prolonged dependence

Transferred dependence

• While less harmful than tobacco, there is a risk of transferring nicotine dependence to the gum

Smoking cessation (drug interactions)

• Stopping smoking may increase blood levels of medicines with a narrow therapeutic window (e.g., theophylline, clozapine) due to changes in CYP1A2 metabolism
• If symptoms persist or get worse, or if new symptoms occur, patients should stop use and consult a health care professional

Effects on ability to drive and use machines

• Nicotine replacement therapy can cause dizziness. Patients should ensure that they know how nicotine replacement therapy affects their ability to drive and use machines, before engaging in these activities

Forms avail. in SA and covered in this monograph: slt, chg

South African registered indications and dosages

Temporary aid to the cigarette smoker seeking to give up their smoking habit while participating in a behavioural modification programme under professional supervision
(Efficacy, without concomitant participation in a behavioural modification programme has not been established)

• Oral (chg): 10-12 pieces, daily (of 2mg or 4mg gum) is sufficient to control the urge to smoke; Gum should be chewed very slowly (over approx. 30mins) until it is tasted or a slight tingling is felt in the mouth; Whenever patient feels the need to smoke, one piece of gum should be placed in the mouth; Treatment duration: 3 months; Max: 15 pieces of chewing gum/24hrs

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Gradual weaning from the gum should then be initiated. Treatment should be stopped when the dose is reduced to 1-2 chewing gums per day

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The benefits of nicotine gum use beyond 3 months has not been demonstrated

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The gum should be chewed slowly for 30 minutes to release most of the nicotine. The patient should not expect the gum to give the same quick satisfaction that smoking does. Depending on the patient’s needs, the rate of chewing and the time between pieces can be adjusted

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Patient must give up smoking completely

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See Additional Prescribing Points for method of administration

Not established for use in children (see Contraindications)

Pregnancy

South African recommendations

Contraindicated

• Nicotine may cause foetal harm when administered to a pregnant woman, it is therefore contraindicated in women who are or may become pregnant, and female patients should be advised to take adequate precautions to avoid becoming pregnant
• The doctor may wish to consider a pregnancy test before instituting therapy with nicotine replacement therapy. If nicotine replacement therapy is used during pregnancy, or if the patient becomes pregnant while taking on this product, the patient should be apprised of the potential hazard to the foetus
• Nicotine passes to the foetus and affects its breathing movements and circulation. The effect on circulation is dose-dependent. Therefore, the pregnant smoker should always be advised to stop smoking completely without use of nicotine replacement therapy
• The risk of continued smoking may pose a greater hazard to the foetus as compared with the use of nicotine replacement products in a supervised smoking cessation programme
• Maternal smoking in pregnancy is associated with low birth weight infants and increased risk of abortion, premature birth, still birth and neonatal death. Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby. The earlier abstinence is achieved the better

Women of childbearing potential/ contraception in males and females

• In contrast to the well-known adverse effects of tobacco smoking on human conception and pregnancy, the effects of therapeutic nicotine treatment are unknown
• Thus, whilst to date no specific advice regarding the need for female contraception has been found to be necessary, the most prudent state for women intending to become pregnant is to be both non-smoking, and not using nicotine replacement therapy (NRT)
• Whilst smoking may have adverse effects on male fertility, no evidence exists that particular contraceptive measures are required during NRT treatment by males

Breastfeeding

South African recommendations

• Caution; not recommended
• Because of the potential for serious adverse reactions to nursing infants from nicotine, a decision should be made whether to discontinue nicotine replacement therapy
• Nicotine passes freely into breast milk in quantities that may affect the infant, even at therapeutic doses, and therefore should not be used by mothers breastfeeding their infants
• As nicotine is the major addictive substance in tobacco smoke, the possibility exists that dependence on the nicotine in nicotine replacement therapy may occur. Should smoking cessation not be achieved, use by breastfeeding smokers should only be initiated after advice from a health care provider
• Women should take nicotine replacement therapy as soon as possible after breastfeeding

Fertility

South African recommendations

• In females, tobacco smoking delays time to conception, decreases in vitro fertilisation success rates, and increases risk of infertility
• In males, tobacco smoking reduces sperm production, increases oxidative stress and DNA damage. Spermatozoa from smokers have reduced fertilising capacity. The specific contribution of nicotine however, to these effects in humans, is unknown

South African recommendations

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

South African recommendations

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; no dose adjustment recommended

South African recommendations

• No dose adjustment recommended

Immune System Disorders

Less frequent

• Allergic reactions (including angioedema)
• Hypersensitivity

Nervous System Disorders

Frequent

• Headache
• Dizziness
• Dysgeusia
• Paraesthesia

Cardiac Disorders

Less frequent

• Palpitations
• Reversible atrial fibrillation

Respiratory, Thoracic and Mediastinal Disorders

Frequent

• Cough
• Throat irritation

Gastrointestinal Disorders

Frequent

• Gastrointestinal discomfort
• Hiccups
• Nausea
• Vomiting
• Diarrhoea
• Abdominal pain
• Dry mouth
• Dyspepsia
• Flatulence
• Stomatitis
• Salivary hypersecretion

Skin and Subcutaneous Tissue Disorders

Less frequent

• Erythema
• Urticaria

General Disorders and Administration Site Conditions

Frequent

• Sore mouth or throat
• Jaw muscle ache
• Burning sensation (at the application site)
• Fatigue

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Post-marketing experience

Immune System Disorders

Frequency unknown

• Anaphylactic reaction

Psychiatric Disorders

Less frequent

• Abnormal dream

Nervous System Disorders

Frequency unknown

• Seizures

Eye Disorders

Less frequent

• Blurred vision
• Increased lacrimation

Cardiac Disorders

Less frequent

• Tachycardia

Vascular Disorders

Less frequent

• Flushing
• Hypertension

Respiratory, Thoracic and Mediastinal Disorders

Less frequent

• Bronchospasm
• Dysphonia
• Dyspnoea
• Nasal congestion
• Oropharyngeal pain
• Sneezing
• Throat tightness

Gastrointestinal Disorders

Less frequent

• Dry throat
• Dysphagia
• Eructation
• Glossitis
• Oral hypoaesthesia
• Oral mucosal blistering and exfoliation
• Lip pain
• Oral paraesthesia
• Retching

Skin and Subcutaneous Tissue Disorders

Less frequent

• Hyperhidrosis
• Pruritus
• Rash

Musculoskeletal, Connective Tissue and Bone Disorders

Less frequent

• Pain in jaw
• Muscle tightness

General Disorders and Administration Site Conditions

Less frequent

• Asthenia
• Chest discomfort and pain
• Malaise

No significant interactions (see Additional Prescribing Points)

None routine. Specific cases may require

• Blood glucose (patients with diabetes mellitus)

Method of administration 

1. The patient must give up smoking completely. The gradual cutting down of tobacco consumption will not work
2. Nicotine gum has been prescribed as part of a programme to help the patient stop smoking
3. Whenever the patient feels the need to smoke, one piece of gum should be placed in the mouth
4. When the gum is chewed, nicotine is slowly released and is absorbed through the lining of the mouth
5. The gum should be chewed very slowly until it is tasted or a slight tingling is felt in the mouth. Because of its nicotine content, the gum does not taste like an ordinary chewing gum
6. As soon as the gum can be tasted, chewing must stop
7. After the taste or tingling is almost gone (about one minute), the gum should be chewed slowly again until the taste is more pronounced. Then chewing should be stopped again
8. The gum should be chewed slowly for 30 minutes to release most of the nicotine. The patient should not expect the gum to give the same quick satisfaction that smoking does
9. Most people find that 10 to 12 pieces per day of nicotine gum 2 mg or 4 mg are enough to control their urge to smoke. If this is not the case, consult your doctor or pharmacist. Do not use more than 15 pieces in 24 hours. Depending on the patient’s needs, the rate of chewing and the time between pieces can be adjusted

Interaction with other medicines and other forms of interaction

• No clinically relevant interactions between nicotine replacement therapy and other medicines has definitely been established
• However, nicotine replacement therapy may possibly enhance the haemodynamic effects of adenosine, i.e. increase in blood pressure and heart rate and also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration
• Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medicines in ex-smokers
• Smoking is considered to increase metabolism and thus lower blood levels of medicines such as caffeine, theophylline, imipramine and pentazocine, through enzyme induction
• Cessation of smoking may result in increased levels of these medicines. Absorption of glutethimide may be decreased and the “first pass” metabolism of propoxyphene decreased by smoking cessation
• Other reported effects of smoking, which do not involve enzyme induction, include reduced diuretic effects of furosemide and decreased cardiac output, and increased blood pressure with propranolol, which may also relate to the hormonal effects of nicotine. Smoking cessation may reverse these actions
• Both smoking and nicotine can increase circulating cortisol and catecholamines. Therapy with adrenergic agonists or with adrenergic blockers may need to be adjusted according to changes in nicotine therapy or smoking status

Nicotine is an agonist at nicotine receptors in the peripheral and central nervous system (CNS) and has pronounced CNS and cardiovascular effects. Abrupt cessation of the established, regular use of tobacco-containing products results in the characteristic syndrome, with withdrawal symptoms including cravings (urges to smoke). Clinical studies have shown that nicotine replacement products can help smokers abstain from or reduce their smoking by relieving these withdrawal symptoms. The majority of smokers will gain weight on stopping smoking. In clinical trials, nicotine replacement therapy has been shown to attenuate post-cessation weight gain. Owing to the slower rate of absorption of nicotine through the buccal mucosa, it does not reproduce the pleasure of cigarette smoking. Although one is still supplying the body with nicotine, the blood levels achieved after repeated administration of nicotine replacement therapy are less than those achieved after smoking.