This product is indicated for the relief of nicotine withdrawal symptoms as an aid to smoking cessation in adults and children over 12 years of age. It is also indicated in pregnant and lactating women (see section 4.6).

In smokers currently unable or not ready to stop smoking abruptly, this product may also be used as part of a programme to reduce smoking prior to stopping completely.

If possible, this product should be used in conjunction with a behavioural support programme.

Behavioural therapy, advice and support will normally improve the success rate.

Smoking cessation

Adults (over 18 years of age)The patient should make every effort to stop smoking completely during treatment with this product .

The initial dose is based on the individual's nicotine dependence. The tablet is used sublingually with a recommended dose of one tablet per hour or, for heavy smokers (smoking more than 20 cigarettes per day), two tablets per hour. Allow the tablet to dissolve slowly (about 30 minutes).You should not swallow or chew the tablet.

Increasing to two tablets per hour may be considered for patients who fail to stop smoking with the one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.

Most smokers require 8 to 12 or 16 to 24 tablets per day, not to exceed 40 tablets. The duration of treatment is individual, but up to three months of treatment is recommended. The nicotine dose should then be gradually reduced, by decreasing the total number of tablets used per day. The treatment should be stopped when the daily consumption is down to one or two tablets.

Adults who use NRT beyond 9 months are recommended to seek additional help and advice from a healthcare professional.

Adolescents (12 to 18 years)

The patient should make every effort to stop smoking completely during treatment with this product.

The initial dose is based on the individual's nicotine dependence. The tablet is used sublingually with a recommended dose of one tablet per hour or, for heavy smokers (smoking more than 20 cigarettes per day), two tablets per hour. Increasing to two tablets per hour may be considered for patients who fail to stop smoking with the one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.

Most smokers require 8 to 12 or 16 to 24 tablets per day, not to exceed 40 tablets. Use for up to 8 weeks to break the habit of smoking, then gradually reduce the dose over a 4 week period. The treatment should be stopped when the daily consumption is down to one or two tablets. As data are limited in this age group, the recommended duration of treatment is 12 weeks. If longer treatment is required, advice from a healthcare professional should be sought.

Smoking reduction

Adults (over 18 years of age)

Use this product between smoking episodes to manage the urge to smoke, to prolong smoke-free intervals and with the intention to reduce smoking as much as possible. If a reduction in 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.

When making a quit attempt the smoking cessation instructions above can be followed.

Adolescents (12 to 18 years)

Where adolescents are motivated to stop smoking abruptly, smoking cessation should be recommended. However, smoking reduction can be considered where adolescents are not ready or able to stop smoking abruptly. As data are limited in this age group, and the recommended duration of NRT is 12 weeks, adolescents should consult a healthcare professional before starting the “ smoking reduction prior to stopping” regimen.

Use this product between smoking episodes to manage the urge to smoke, to prolong smoke-free intervals and with the intention to reduce smoking as much as possible. If a reduction in 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.

When making a quit attempt the smoking cessation instructions for adolescents (12 to 18 years) given above can be followed.

Hypersensitivity to any component of the sublingual tablet.

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

A risk-benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:

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 have 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 smoking is stopped and NRT is initiated as reductions in nicotine induced catecholamine release can affect carbohydrate metabolism.

GI disease: Nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis or peptic ulcers and 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.

Seizures: Potential risks and benefits of nicotine should be carefully evaluated

before use in subjects with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

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

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.

No clinically relevant interactions between nicotine replacement therapy and other drugs have 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.

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

NRT is not contraindicated in pregnancy. The decision to use NRT should be made on a risk-benefit assessment as early on in the pregnancy as possible with the aim of discontinuing use as soon as possible.

Smoking during pregnancy is associated with risks such as intra-uterine growth retardation, premature birth or stillbirth. Stopping smoking is the single most effective intervention for improving the health of both pregnant smoker and her baby. The earlier abstinence is achieved the better.

Ideally smoking cessation during pregnancy should be achieved without NRT. Nicotine passes to the foetus and affects its breathing movements and circulation. The effect on the circulation is dose-dependent. However for women unable to quit on their own, NRT may be recommended to assist a quit attempt, the risk of using NRT to the fetus is lower than that expected with tobacco smoking, due to lower maximal plasma nicotine concentration and no additional exposure to polycyclic hydrocarbons and carbon monoxide.

Intermittent dosing products may be preferable as these usually provide a lower daily dose of nicotine than patches. However, patches may be preferred if the woman is suffering from nausea during pregnancy. If patches are used they should be removed before going to bed.

Use of nicotine by the pregnant smoker should only be initiated after advice from a health care professional.

Lactation

Nicotine should be avoided during breast-feeding.

However, NRT is not contraindicated in lactation. Nicotine from smoking and NRT is found in breast milk. However the amount of nicotine the infant is exposed to is relatively small and less hazardous than the second-hand smoke they would otherwise be exposed to.

Using intermittent dose NRT preparations, compared with patches, may minimize the amount of nicotine in the breast milk as the time between administrations of NRT and feeding can be more easily prolonged.

Use of the nicotine by breast feeding smokers should only be initiated after advice from a health care professional. Women should take the product as soon as possible after breastfeeding.

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

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, decreased heart rate, dizziness, presyncopal symptoms, cough, constipation, gingival bleeding or nasopharyngitis.

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. 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.

Most of the undesirable effects associated with this product occur during the first 3-4 weeks after starting treatment. Irritation in the mouth and throat may be experienced, however most subjects adapt to this with ongoing use.

Allergic reactions (including symptoms of anaphylaxis) can occur during the use of the product.

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.

^a Systemic effects; ^b Tightness of jaw and pain in jaw with nicotine gum formulation

^c At the application site

^*Identified only for formulations applied during the night

^**Higher frequency observed in clinical studies with inhaler formulation.

***Reported the same or less frequently than placebo

**** Higher frequency observed in clinical studies with mouth spray formulation

^# Although the frequency in the active group is less than that of the placebo group, the frequency in the specific formulation in which the PT was identified as a systemic ADR was greater in the active group than the placebo group.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms: Symptoms of overdose with nicotine from this product may occur in smokers who have previously had a low nicotine intake from cigarettes or if other sources of nicotine are used concomitantly with this product.

Acute or chronic toxicity of nicotine in man is highly dependent on mode and route of administration. Adaptation to nicotine (e.g. in smokers) is known to significantly increase tolerability compared with non-smokers. 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, vomiting, increased 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.

Doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in children and may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.

Pharmacotherapeutic group: Drug used in nicotine dependence.

ATC code: N07B A01

The pharmacological effects of nicotine are well documented. Those resulting from using this product are comparatively small. The response at any one time represents a summation of stimulant and depression actions from direct, reflex and chemical mediator influences on several organs. The principal 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.

Most of the absorption of nicotine from this product occurs directly through the buccal mucosa. The absolute bioavailability, after sublingual administration of the tablet, is approximately 50%. The systemic bioavailability of orally administered nicotine is lower due to the amount removed initially by the liver (the first-pass effect). Hence, the high and rapidly rising nicotine concentrations seen after smoking are rarely produced by treatment with this product.

Nicotine from smoking is rapidly absorbed from the lungs into arterial plasma whereas nicotine from sublingual tablets passes more slowly into the venous system.

Steady-state trough nicotine plasma concentrations, achieved after ten hourly doses of one tablet, are in the order of magnitude of 10 ng/mL, which is about 50% of normal smoking levels.

There is a slight deviation from dose-linearity of AUC_inf and C_max when single doses of one, two and three tablets are given. This deviation may be explained by a larger fraction of the higher doses being swallowed and subject to first-pass elimination.

The therapeutic blood concentrations of nicotine, i.e. the blood levels which relieve craving, are based on the individual's nicotine dependence.

Preclinical data indicate that nicotine is neither mutagenic nor genotoxic.

Crospovidone

ß -cyclodextrin

Colloidal anhydrous silica

Magnesium stearate

Not applicable.

Two (2) years.

Do not store above 25° C.

Aluminium foil/PVC-PVDC circular-shaped blister strips (discs) of fifteen (15) tablets assembled in cartons, together with a dispenser. The dispenser is used to remove the tablets from the disc.

Package sizes

30 Tablets (two strips), together with the dispenser.

105 Tablets (seven strips), together with the dispenser.

Or

Al/Al blister strips of 10 sublingual tablets.

Package sizes

Cardboard box of 10, 20, 30, 90, 100, 150 or 210 sublingual tablets with a package insert/booklet.

Not all pack sizes may be marketed.

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