SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Nicorette Freshfruit 4 mg Gum Nicorette Fruitfusion 4mg Gum Boots NicAssist Fruit Fresh 4 mg Gum

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Chewing Gum containing 4mg nicotine, as nicotine resinate.

For excipients, see 6.1.

3    PHARMACEUTICAL FORM

Medicated Chewing Gum A square, coated, creme coloured piece of gum

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

This product 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.

This product is indicated in pregnant and lactating women making a quit attempt.

4.2 Posology and method of administration

Adults and Children over 12 years of age

This product should be chewed slowly according to the instructions.

The strength of gum to be used will depend on the smoking habits of the individual. In general, if the patient smokes 20 or less cigarettes a day, 2mg nicotine gum is indicated. If more than 20 cigarettes per day are smoked, 4mg nicotine gum will be needed to meet the withdrawal of the high serum nicotine levels from heavy smoking.

This product should be used whenever the urge to smoke is felt or to prevent cravings in situations where these are likely to occur.

Smokers willing or able to stop smoking immediately should initially replace all their cigarettes with the Gum and as soon as they are able, reduce the number of gums used until they have stopped completely.

Smokers aiming to reduce cigarettes should use this product, as needed, between smoking episodes to prolong smoke-free intervals and with the intention to reduce smoking as much as possible.

As soon as they are ready smokers should aim to quit smoking completely. Maximum daily dose: 15 pieces per day.

When making a quit attempt behavioural therapy, advice and support will normally improve the success rate. Those who have quit smoking, but are having difficulty discontinuing this product are recommended to contact their pharmacist or doctor for advice.

For those using the 4mg gum, switching to the 2mg gum may be helpful when stopping treatment or reducing the number of gums used each day.

The chewing gums should be used whenever there is an urge to smoke according to the “chew and rest” technique described on the pack. After about 30 minutes of such use, the gum will be exhausted. Absorption of nicotine is through the buccal mucosa, any nicotine which is swallowed being destroyed by the liver.

4.3 Contraindications

Hypersensitivity to nicotine or any component of the chewing gum. This product is contraindicated in children under the age of 12 years.

4.4 Special warnings and precautions for use

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

Underlying cardiovascular disease: In stable cardiovascular disease this product presents a lesser hazard than continuing to smoke. However dependent smokers currently hospitalised as a result of myocardial infarction, unstable or worsening angina including Prinzmetal’s angina, severe dysrhythmia or CVA and who are considered to be haemodynamically unstable and/or who suffer with uncontrolled hypertension should be encouraged to stop smoking with non-pharmacological interventions. If this fails, this product 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 NRT is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.

GI disease: Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis or peptic ulcers and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.

Renal or hepatic impairment: This product 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. Nicotine gum should be disposed of with care.

Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, this product should be used with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma.

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 metabolised by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops smoking, this may result in slower metabolism and a consequent rise in blood levels of such drugs. This is of potential clinical importance for products with a narrow therapeutic window, e.g. theophylline, clozapine and ropinirole.

Excipients: This product also contains butylated hydroxy toluene (E321); this may cause irritation to the mucous membranes.

Denture warning: Smokers who wear dentures may experience difficulty in chewing this product. The chewing gum may stick to, and may in rare cases damage dentures.

4.5 Interaction with other medicinal products and other forms of interaction

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 i.e. increase in blood pressure and heart rate and

also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration.

4.6 Fertility, Pregnancy and lactation

Fertility

In females tobacco smoking delays time to conception, decreases in-vitro fertilization success rates, and significantly increases the risk of infertility.

In males tobacco smoking reduces sperm production, increases oxidative stress, and DNA damage. Spermatozoa from smokers have reduced fertilizing capacity.

The specific contribution of nicotine to these effects in humans is unknown. 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. Ideally smoking cessation during pregnancy should be achieved without NRT. 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 if this is not achievable this product 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.

4.7 Effects on ability to drive and use machines

This product has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Effects of Smoking Cessation

Some symptoms may be related to nicotine withdrawal associated with stopping smoking. These can include; irritability/aggression, dysphoria/depressed mood, anxiety, restlessness, poor concentration, increased appetite/weight gain, urges to smoke (cravings), night-time awakenings/sleep disturbance and decreased heart rate.

Increased frequency of aphthous ulcer may occur after abstinence from smoking. The causality is unclear.

Adverse Drug Reactions

This product may cause adverse reactions similar to those associated with nicotine given by other means, including smoking, and these are mainly dose-dependent. At recommended doses this product has not been found to cause any serious adverse effects. Most of the undesirable effects reported by the patients occur during the first 3-4 weeks after start of treatment.

Excessive consumption of this product by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches. Excessive swallowing of dissolved nicotine may, at first, cause hiccupping.

Nicotine from the gum may sometimes cause a slight irritation of the throat at the start of treatment and may also cause increased salivation.

Those who are prone to indigestion may suffer initially from minor degrees of indigestion or heartburn if the 4mg nicotine gum is used; slower chewing and the use of the 2mg nicotine gum (if necessary more frequently) will usually overcome this problem.

The chewing gum may stick to, and may in rare cases damage dentures.

The adverse reactions observed in patients treated with oral nicotine formulations during clinical trials and post-marketing experience are listed below by system organ class (SOC). Frequencies are defined in accordance with current guidance, as: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1 000, <1/100); rare (>1/10 000, <1/1 000); very rare (<1/10 000), Not known - cannot be estimated from the available data.

System Organ Class	Reported Adverse Event	Incidence
Immune System Disorders	Hypersensitivitya	Common
	Anaphylactic reactiona	Not known
Psychiatric disorders	Abnormal dreams	Uncommon
Nervous System Disorders	Headachea#	Very Common
	Burning sensationc	Common
	Dizziness	Common
	Dysgeusia	Common
	Paraesthesiaa	Common
Eye Disorders	Blurred Vision	Not known
	Lacrimation increased	Not known
Cardiac Disorders	Palpitationsa	Uncommon
	Tachycardiaa	Uncommon
	Reversible atrial fibrillation	Very Rare
Vascular Disorders	Flushinga	Uncommon
	Hypertensiona	Uncommon

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms: The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 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 an overdose: All nicotine intake should stop immediately and the patient should be treated symptomatically. Artificial respiration should be instituted if necessary. Activated charcoal reduces the gastro-intestinal absorption of nicotine.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in nicotine dependence ATC code: N07B A01

The pharmacological effects of nicotine are well documented. Those resulting from chewing this product are comparatively small. The response at any one time represents a summation of stimulant and depressant actions from direct, reflex and chemical mediator influences on several organs. The main pharmacological actions are central stimulation and/or depression; transient hyperpnoea; peripheral vasoconstriction (usually associated with a rise in systolic pressure); suppression of appetite and stimulation of peristalsis.

Increased appetite is a recognised symptom of nicotine withdrawal and postcessation weight gain is common. Clinical trials have demonstrated that Nicotine Replacement Therapy can help control weight following a quit attempt.

5.2 Pharmacokinetic properties

Nicotine administered in chewing gums is readily absorbed from the buccal mucous membranes. Demonstrable blood levels are obtained within 5-7 minutes and reach a maximum about 30 minutes after the start of chewing. Blood levels are roughly proportional to the amount of nicotine chewed and have been shown never to exceed those obtained from smoking cigarettes.

5.3 Preclinical safety data

Preclinical data indicate that nicotine is neither mutagenic nor genotoxic.

There are no other findings derived from preclinical testing of relevance to the prescriber in determining the safety of the product which have not been considered in other relevant sections of this Summary of Product Characteristics.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Core Gum

Chewing gum base, containing butylated hydroxy toluene (E321) Xylitol

Peppermint oil

Sodium carbonate, anhydrous Acesulfame Potassium Levomenthol Magnesium oxide, light Quinoline yellow Al-Lake (E104)

Talc

Sub-coating Tuttifrutti QL84441 Hypromellose Sucralose Polysorbate 80 Purified water

Coating

Xylitol

Acacia

Titanium dioxide (E171)

Tuttifrutti QL84441 Quinoline yellow Al-lake (E104)

Carnauba wax Purified Water

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

Blister: 3 Years

Box: 3 Years. Shelf life after opening 3 months.

6.4    Special precautions for storage

Do not store above 25^oC.

6.5    Nature and contents of container

PVC/PVDC/Al Blister packed strips each containing 15 pieces supplied in packs of 15, 30, 105 and 210 pieces.

Blister packed strips each containing 6 pieces supplied in packs of 12 pieces.

Blister packed strips each containing 10 pieces supplied in packs of 10 pieces. and

Laminated cardboard box, wrapped in a transparent plastic film, containing 25 pieces, supplied in packs of 25, 100 and 200.

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

Dispose of Nicorette Gum sensibly.

Any unused product or waste material should be disposed of in accordance with local requirements.

7    MARKETING AUTHORISATION HOLDER

McNeil Products Limited Foundation Park Roxborough Way Maidenhead Berkshire SL6 3UG United Kingdom

8    MARKETING AUTHORISATION NUMBER(S)

PL 15513/0137

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

18/07/2006

DATE OF REVISION OF THE TEXT

18/05/2016