SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Nicotinell Tropical fruit 4 mg medicated chewing-gum

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each piece of medicated chewing-gum contains:

Active substance: 4 mg nicotine (as 20 mg nicotine polacrilin (1:4)). Excipient(s): sorbitol (0.1 g), sodium (11.45 mg) and butylhydroxytoluene (E321)

For a full list of excipients, see section 6.1

3    PHARMACEUTICAL FORM

Medicated chewing-gum.

The coated chewing-gum is off-white in colour and rectangular in shape.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Treatment of tobacco dependence by providing relief of nicotine craving and nicotine withdrawal symptoms, and by facilitating smoking cessation in smokers motivated to stop smoking or facilitating smoking reduction in smokers who cannot or are reluctant to stop.

4.2 Posology and method of administration

Adults and elderly

Users should stop smoking completely during treatment with Nicotinell Tropical fruit medicated chewing-gum.

The dosage should be chosen on the basis of the patient’s nicotine dependence. The 4 mg medicated chewing-gum is intended to be used by smokers with a strong nicotine dependency and by those who have previously failed to stop smoking with the 2 mg gum. In other cases, the 2 mg gum shall be used.

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

Low to moderate

dependen^cy    Moderate to strong dependency    Strong to very strong

dependency

Less than 20

tigarettes / da^y    From 20 to 30 cigarettes / day

Low dose forms are

preferable    Low (2 mg gum) or high (4 mg gum) dose forms are acceptable

(^{2 mg} gum)    depending on patient characteristics and preference.

If an adverse event occurs with the use of the high dose form, use of the low dose form should be considered.

The initial dosage should be individualized on the basis of the patient’s nicotine dependence.

One piece of Nicotinell Tropical fruit medicated chewing-gum to be chewed when the user feels the urge to smoke.

Normal use is 8-12 pieces per day, up to a maximum of 15 pieces a day for the 4 mg gum and 25 pieces per day for the 2 mg gum.

The characteristics of medicated 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.

Smoking cessation

The treatment duration is individual. Normally, treatment should continue for at least 3 months. After 3 months, the users should gradually reduce the nicotine dose. Treatment should be discontinued when the dose has been reduced to 1-2 pieces of medicated chewing-gum per day. Regular use of Nicotinell Tropical fruit medicated chewing-gum beyond 1 year is generally not recommended. Some ex-smokers may need treatment with the medicated chewing-gum for longer to avoid returning to smoking. Remaining gums should be kept, since the urge to smoke may return suddenly. Counselling may improve the chance for smokers to quit.

Smoking reduction:

Nicotinell Tropical fruit medicated chewing-gum should be used between periods of smoking in order to prolong smoke-free intervals and with the intention of reducing smoking as much as possible. If a reduction in the number of cigarettes per day has not been achieved after 6 weeks, professional advice should be sought. A quit attempt should be made as soon as the smoker feels ready, but not later than 6 months after start of treatment. If a quit attempt cannot be made within 9 months after starting treatment, professional advice should be sought. Regular use of Nicotinell Tropical fruit medicated chewing-gum beyond 1 year is generally not recommended. Some ex-smokers may need treatment with the medicated

chewing-gum for longer to avoid returning to smoking. Remaining gums should be kept, since the urge to smoke may return suddenly. Counselling may improve the chance for smokers to quit.

Directions for use:

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

2.    The medicated 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.

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 medicated chewing-gum.

Children and adolescents (< 18 years)

Nicotinell Tropical fruit medicated chewing-gum should not be used by people under 18 years of age without recommendation from a physician. There is no experience in treating adolescents under the age of 18 years with Nicotinell Tropical fruit medicated chewing-gum.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients. Nicotinell Tropical fruit medicated chewing-gum should not be used by non-smokers.

4.4 Special warnings and precautions for use

Dependent smokers with a recent myocardial infarction, unstable or worsening angina (including Prinzmetal’s angina), severe cardiac arrhythmias, uncontrolled hypertension or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, Nicotinell Tropical fruit medicated chewing-gums may be considered. As data on safety in this patient group are limited, initiation should only be under close medical supervision.

Nicotinell Tropical fruit medicated chewing-gums should be used with caution in patients with hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease, heart failure, diabetes mellitus, hyperthyroidism or pheochromocytoma and severe hepatic and/or renal impairment.

Patients should initially be encouraged to stop smoking with non-pharmacological interventions (such as counselling).

Swallowed nicotine may exacerbate symptoms in subjects suffering from active oesophagitis, oral or pharyngeal inflammation, gastritis or peptic ulcer.

Doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in small children and may prove fatal (see section 4.9).

People having problems with the joint of the jawbone and denture wearers, may experience difficulty in chewing the medicated chewing-gum In this case, it is recommended that they use a different pharmaceutical form of nicotine replacement therapy.

Special warnings about excipients

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

Nicotinell Tropical fruit medicated chewing-gum contains sugar substitute, including 0,1 g sorbitol (E420) per medicated chewing-gum, a source of 0.02 g fructose. Calorific value 1.0 kcal/piece of medicated chewing-gum (Nicotinell Tropical fruit 2 mg) and 0.9 kcal/piece of medicated chewing-gum (Nicotinell Tropical fruit 4 mg) respectively.

Nicotinell Tropical fruit medicated chewing-gum contains sodium 11.44 and 11.45 mg per piece respectively (Nicotinell Tropical fruit 2 mg and Nicotinell Tropical fruit 4 mg respectively). To be taken into consideration by patients on a controlled sodium diet.

The gum base contains butylhydroxytoluene (E321) which may cause local irritation to mucous membranes.

4.5 Interaction with other medicinal products and other forms of interaction

Drug Interactions: No information is available on interactions between Nicotinell Tropical fruit medicated chewing-gum and other medicinal products.

Smoking but not nicotine is associated with increased CYP1A2 activity. After stopping smoking there may be reduced clearance of substrates for this enzyme and increased plasma levels of some medicinal products of potential clinical importance because of their narrow therapeutic window e.g. theophylline, tacrine, olanzapine and clozapine.

The plasma concentrations of other active substances metabolised by CYP1A2 e.g. caffeine, paracetamol, phenazone, phenylbutazone, pentazocine, lidocaine, benzodiazepines, warfarin, oestrogen and vitamin B12 may also increase after stopping smoking. However the clinical significance of this effect is unknown. Smoking may lead to reduced analgesic effects of propoxyphene, reduced diuretic response to furosemide, reduced effect of propranolol on blood pressure and heart rate and reduced responder rates in ulcer healing with H2-antagonists.

Smoking and nicotine may raise the blood levels of cortisol and catecholamines, i.e. may lead to a reduced effect of nifedipine or adrenergic antagonists and to an increased effect of adrenergic agonists.

Increased subcutaneous absorption of insulin which occurs upon smoking cessation may necessitate a reduction in insulin dose.

4.6 Pregnancy and lactation

Pregnancy

In pregnant women complete cessation of tobacco smoking should always be recommended without nicotine replacement therapy. Nevertheless, in the case of failure in highly dependent pregnant smokers, tobacco withdrawal via nicotine replacement therapy may be recommended. Indeed, foetal risk is probably lower than that expected with tobacco smoking, due to:

-    lower maximal plasma nicotine concentration than with inhaled nicotine

-    no additional exposure to polycyclic hydrocarbons and carbon monoxide

-    improved chances of quitting smoking by the third trimester.

Smoking continued during the third trimester may lead to intra-uterine growth retardation or even premature birth or stillbirth, depending on the daily amount of tobacco.

Tobacco withdrawal with or without nicotine replacement therapy should not be undertaken alone but as part of a medically supervised smoking cessation program.

In the third trimester nicotine has haemodynamic effects (e.g. changes in foetal heart rate) which could affect the foetus close to delivery. Therefore, after the sixth month of pregnancy, the medicated chewing-gum should only be used under medical supervision in pregnant smokers who have failed to stop smoking by the third trimester.

Lactation

Nicotine is excreted in breast milk in quantities that may affect the child even in therapeutic doses. Nicotinell Tropical fruit medicated chewing-gum, like smoking itself, should therefore be avoided during breast-feeding. Should smoking withdrawal not be achieved, use of the medicated chewing-gum by breast-feeding smokers should only be initiated after advice from a physician. Where nicotine replacement therapy is used whilst breast-feeding, the medicated chewing-gum should be taken just after breast-feeding and not during the two hours before breast-feeding.

Effects on ability to drive and use machines

Smoking cessation can cause behavioral changes. There is no evidence of any risks associated with driving or operating machinery when the medicated chewing-gum is used following the recommended dose.

4.8 Undesirable effects

Nicotinell Tropical fruit medicated chewing-gum can cause adverse reactions similar to those associated with nicotine administered by smoking. These can be attributed to the pharmacological effects of nicotine, which are dose-dependent.

Non dose-dependent adverse reactions are as follows: jaw muscle ache, erythema, urticaria, hypersensitivity, angioneurotic oedema and anaphylactic reactions.

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.

Excessive swallowing of nicotine which is released in the saliva may, at first, cause hiccups. Those who are prone to indigestion may suffer initially from minor degrees of dyspepsia or heartburn; slower chewing will usually overcome this problem.

Excessive consumption of nicotine medicated chewing-gums by subjects who have not been in the habit of inhaling tobacco smoke, could possibly lead to nausea, faintness and headache.

Increased frequency of aphthous ulcer may occur after abstinence from smoking.

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

Common (>1/100 to <1/10)

Nervous system disorders: headache, dizziness

Gastrointestinal disorders: hiccups, gastric symptoms e.g. nausea, flatulence, vomiting, dyspepsia, salivary hypersecretion, stomatitis, oral pain, or pharyngolaryngeal pain

Musculoskeletal and connective tissue disorders: jaw muscle ache

Uncommon (>1/1,000 to <1/100) Cardiac disorders: palpitations

Rare (>1/10,000, <1/1,000)

Immune system disorders: hypersensitivity, angioneurotic oedema and anaphylactic reactions

Cardiac disorders: atrial arrhythmia (e.g. atrial fibrillation)

Certain symptoms which have been reported such as dizziness, headache and insomnia may be ascribed to withdrawal symptoms in connection with smoking cessation and may be due to insufficient administration of nicotine.

Cold sores may develop in connection with smoking cessation, but any relation with the nicotine treatment is unclear.

The patient may still experience nicotine dependence after smoking cessation.

4.9 Overdose

In overdose, symptoms corresponding to heavy smoking may be seen.

The acute lethal oral dose of nicotine is about 0.5 - 0.75 mg per kg bodyweight, corresponding in an adult to 40 - 60 mg. Even small quantities of nicotine are dangerous in children, and may result in severe symptoms of poisoning which may prove fatal. If poisoning is suspected in a child, a doctor must be consulted immediately.

Overdose with Nicotinell Tropical fruit medicated chewing-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 medicated chewing-gum is small. Since the release of nicotine from the medicated chewing-gum is slow, very little nicotine is absorbed from the stomach and intestine, and if any is, it will be inactivated in the liver.

General symptoms of nicotine poisoning include: weakness, perspiration, salivation, throat burn, nausea, vomiting, diarrhoea, abdominal pain, hearing and visual disturbances, headache, tachycardia and cardiac arrhythmia, dyspnoea, prostration, circulatory collapse, coma and terminal convulsions. Treatment of overdose

Symptoms of overdose may develop rapidly, especially in children. Emesis is usually spontaneous. Administration of oral activated charcoal and gastric lavage should be considered as soon as possible and within 1 hour of ingestion. Monitor vital signs and treat symptomatically.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in nicotine dependence ATC Code: N07BA01

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 medicated chewing-gum replaces part of the nicotine that would have been administrated via tobacco and reduces the intensity of the withdrawal symptoms and smoking urge.

5.2 Pharmacokinetic properties

When the medicated chewing-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 a 2 mg medicated chewing-gum is approximately 6.4 nanograms per ml (after approximately 45 minutes). The nicotine peak plasma mean concentration after a single dose of a 4 mg medicated chewing-gum is approximately 9.3 nanograms per ml (after approximately 60 minutes). (The 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 halflife is approximately three hours. Nicotine crosses the blood-brain barrier, the placenta and is detectable in breast milk.

5.3 Preclinical safety data

Nicotine was positive in some in vitro genotoxicity tests but there are also negative results with the same test systems. Nicotine was negative in standard 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.

PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Gum base (containing butylhydroxytoluene (E321)) Xylitol

Calcium Carbonate (E170)

Sorbitol (E420)

Mannitol (E421)

Sodium Carbonate Anhydrous Sodium Hydrogen Carbonate Natural Mint Flavouring Polacrilin Glycerol (E422)

Sucralose

Levomenthol

Mango

Gelatine

Titanium dioxide (E171)

Acesulfame potassium (E950)

Carnauba wax Talc

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

The medicated chewing-gum is packed in PVC/PVdC/aluminium blisters each containing 12 pieces of medicated chewing-gum. The blisters are packed in boxes containing 12, 24, 48, 84, 96 and 204 pieces of medicated chewing-gum.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Used Nicotinell medicated chewing-gum should be disposed of with care.

7 MARKETING AUTHORISATION HOLDER

Novartis Consumer Health UK Ltd,

Park View,

Riverside Way,

Watchmoor Park,

Camberley,

Surrey GU15 3YL

8    MARKETING AUTHORISATION NUMBER(S)

PL 00030/0450

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION 17/05/2011

10 DATE OF REVISION OF THE TEXT

04/07/2013