Nicotinell^® Mint 2mg Medicated Chewing Gum

One piece of medicated chewing gum contains 2 mg nicotine (as 10 mg nicotine – polacrilin (1:4)).

For excipients, see section 6.1

Medicated chewing gum.

Each piece of coated chewing gum is off-white in colour and rectangular in shape.

Nicotinell gum relieves and/or prevents craving and nicotine withdrawal symptoms associated with tobacco dependence. It is indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.

Nicotinell gum is indicated in pregnant and lactating women making a quit attempt.

Nicotinell gum should preferably be used in conjunction with a behavioural support programme.

Adults and elderly

Users should stop smoking completely during treatment with Nicotinell gum.

One piece of Nicotinell gum to be chewed when the user feels the urge to smoke. Normally, 8-12 pieces per day can be used, up to a maximum of 25 pieces per day.

The 2 mg chewing gum may not be well suited to smokers with a strong or very strong nicotine dependency.

The 4 mg chewing gum is intended to be used by smokers with a strong or very strong nicotine dependency and those who have previously failed to stop smoking with the aid of nicotine replacement therapy.

The optimal dosage form is selected according to the following table:

If an adverse event is noted when high dose forms are initiated, this should be replaced by the lower dosage form.

The characteristics of chewing-gum as a pharmaceutical form are such that individually different nicotine levels can result in the blood. Therefore, dosage frequency should be adjusted according to individual requirements within the stated maximum limit.

Directions for use:

1. One piece of gum should be chewed until the taste becomes strong.

2. The chewing gum should be rested between the gum and cheek.

3. When the taste fades, chewing should commence again.

4. The chewing routine should be repeated for 30 minutes.

The treatment time is individual. Normally, treatment should continue for at least 3 months.

After three months, the user should gradually cut down the number of pieces chewed each day until they have stopped using the product.

Treatment should be discontinued when the dose has been reduced to 1-2 pieces of gum per day. Nicotinell gum is sugar free.

Adolescents (aged 12-18 years of age)

The above recommendation can be used for adolescents aged between 12 and 18 years of age. As data are limited in this age group, medical advice should be obtained should it be found necessary to use the gum beyond 12 weeks.

Concomitant use of acidic beverages such as coffee or soda may decrease the buccal absorption of nicotine. Acidic beverages should be avoided for 15 minutes prior to chewing the gum.

Hypersensitivity to nicotine or any components of the gum.

Nicotinell gum should not be used by non-smokers.

Any risks that may be associated with nicotine replacement therapy are substantially outweighed by the well established dangers of continued smoking.

Precautions: Users should stop smoking completely during therapy with Nicotinell gum. They should be informed that if they continue to smoke while using the gums they may experience increased adverse effects due to the hazards of smoking, including cardiovascular effects.

Cardiovascular disease

In stable cardiovascular disease Nicotinell gum presents a lesser hazard than continuing to smoke. However dependant smokers currently hospitalised as a result of a recent myocardial infarction, severe disrythmia, or recent cerebrovascular accident who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, Nicotinell gum may be considered but as data on safety in this patient group are limited, initiation should only be under medical supervision.

Diabetes mellitus

Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when nicotine replacement therapy is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

Allergic reactions

Angioedema and urticaria have been reported.

Gastro-intestinal disease

Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis, or peptic ulcers and oral nicotine replacement therapy preparations should be used with caution in these conditions. Ulcerative stomatitis have been reported.

Renal and or hepatic impairment

Should be used with caution in patients with moderate to severe hepatic impairment and/or severe renal impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.

Danger in small children

Doses of nicotine tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Products containing nicotine should not be left where they may be misused, handled or ingested by children. Nicotinell gum should be disposed of with care.

Pheochromocytoma and uncontrolled hyperthyroidism

Nicotinell gum should be used with caution in patients with uncontrolled hyperthyroidism or pheochromocytoma as nicotine causes the release of catecholamines.

Transferred dependence

Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Stopping smoking

Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly CYP 1A1). When a smoker stops, this may result in slower metabolism and a consequential rise in blood levels of drugs such as theophylline, tacrine, olanzaprine and clozaprine.

Other warnings

If denture wearers experience difficulty in chewing the gum, it is recommended that they use a different pharmaceutical form of nicotine replacement therapy.

Patients with rare hereditary problems of fructose intolerance should not take this medicine.

Nicotinell 2mg gum contains sorbital (E420) 0.2g per gum, a source of 0.04g fructose. Calorific value 1.0 kcal/piece of gum.

Nicotinell 2mg gum contains sodium 11.50 mg per piece of gum.

No information is available on interactions between Nicotinell gum and other drugs. No clinically relevant interactions between nicotine replacement therapy and other drugs has definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.

Pregnancy

Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the fetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but Nicotinell gums may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the fetus would not normally be exposed to nicotine.

Lactation

The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest.

Not applicable.

Some symptoms such as dizziness, headache and sleep disturbances may be related to the withdrawal of nicotine associated with stopping smoking.

In principle, Nicotinell gums can cause adverse reactions similar to those associated with nicotine administered by other means (including smoking) and these are mainly dose dependant. At recommended doses Nicotinell gum has not been found to cause any serious adverse effects. Excessive consumption of Nicotinell gum by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

Most of the side effects which are reported by patients occur generally during the first 3-4 weeks after initiation of therapy.

Nicotine from gums may sometimes cause a slight irritation of the throat and increase salivation at the start of the treatment.

The gum may stick to and in rare cases damage dentures and dental appliances.

Common (> 1/100).

Nervous system disorders: headache, dizziness

Gastrointestinal disorders: hiccups, gastric symptoms e.g. nausea, vomiting, indigestion, heartburn, increased salivation, irritation or sore mouth or throat

Musculoskeletal, connective and bone disorders: jaw muscle ache.

Uncommon (>1/1,000, <1/100)

Cardiac disorders: palpitations

Skin and subcutaneous tissue disorders: erythema, urticaria

Rare (<1/1,000)

Cardiac disorders: cardiac arrhythmias (e.g. atrial fibrillation)

Immune system disorders: hypersensitivity, angioneurotic oedema and anaphylactic reactions.

In overdose, symptoms corresponding to heavy smoking may be seen, however the toxicity of nicotine cannot be directly compared with that of smoking, because tobacco smoke contains additional toxic substances (eg. carbon monoxide and tar).

Overdose with Nicotinell gum may only occur if many pieces are chewed simultaneously. Nicotine toxicity after ingestion will most likely be minimized as a result of early nausea and vomiting that occur following excessive nicotine exposure. Risk of poisoning by swallowing the gum is small. Since the release of nicotine from the gum is slow, very little nicotine is absorbed from the stomach and intestine, and if any is, it will be inactivated in the liver.

Chronic smokers can tolerate doses of nicotine that, in a non-smoker, would be more toxic, because of the development of tolerance.

Symptoms

The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40-60mg. Symptoms of acute nicotine poisoning include nausea, salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. In extreme cases, these symptoms may be followed by hypotension, rapid or weak or irregular pulse, breathing difficulties, prostration, circulatory collapse and terminal convulsions.

Management of overdose

Following overdose, symptoms may be rapid particularly in children. All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine.

ATC Code: N07B A01

Pharmacotherapeutic group: Drugs used in nicotine dependence

Nicotine, the primary alkaloid in tobacco products and a naturally occurring autonomous substance, is a nicotine receptor agonist in the peripheral and central nervous systems and has pronounced CNS and cardiovascular effects. On consumption of tobacco products, nicotine has proven to be addictive, resulting in craving and other withdrawal symptoms when administration is stopped. This craving and these withdrawal symptoms include a strong urge to smoke, dysphoria, insomnia, irritability, frustration or anger, anxiety, concentration difficulties agitation and increased appetite or weight gain. The gum replaces part of the nicotine that would have been administrated via tobacco and reduces the intensity of the withdrawal symptoms and smoking urge.

When the gum is chewed, nicotine is steadily released into the mouth and is rapidly absorbed through the buccal mucosa. A proportion, by the swallowing of nicotine containing saliva, reaches the stomach and intestine where it is inactivated.

The nicotine peak plasma mean concentration after a single dose of the 2 mg coated gum is approximately 6.4 nanograms per ml (after 45 minutes) (average plasma concentration of nicotine when smoking a cigarette is 15-30 nanograms per ml).

Nicotine is eliminated mainly via hepatic metabolism; small amounts of nicotine are eliminated in unchanged form via the kidneys. The plasma half-life is approximately three hours. Nicotine crosses the blood-brain barrier, the placenta and is detectable in breast milk.

No definite conclusion can be drawn on the genotoxic activity of nicotine in vitro. Nicotine was negative in in-vivo tests.

Animal experiments have shown that nicotine induces post-implantation loss and reduces the growth of foetuses.

The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine.

Gum base (containing butylhydroxytoluene)

Calcium carbonate

Sorbitol (E420)

Sodium carbonate anhydrous

Sodium hydrogen carbonate

Polacrilin,

Glycerol

Purified water

Levomenthol

Peppermint oil

Eucalyptus oil

Saccharin

Sodium saccharin

Acesulfame potassium

Xylitol

Mannitol (E421)

Gelatin

Titanium dioxide (E171)

Carnauba wax

Talc.

Not applicable.

2 years.

Do not store above 25°C.

The chewing-gum is packed in PVC/PVdC/aluminium blisters each containing either 2 or 12 pieces of gum. The blisters are packed in boxes containing 2, 12, 24, 36, 48, 60, 72, 84, 96 108, 120 and 204 pieces of gum.

Not all pack sizes may be marketed.

No special requirements.

Novartis Consumer Health UK Ltd

Trading as Novartis Consumer Health

Wimblehurst Road,

Horsham,

West Sussex RH12 5AB

PL 00030/0427

8 December 2006

8^th December 2010

GSL