4.1. Therapeutic indications

This product relieves and/or prevents craving and nicotine withdrawal symptoms in nicotine dependence, such as those arising from the use of tobacco or electronic cigarettes. It is indicated to aid quitting or reduction prior to quitting, to assist those who are unwilling or unable to use such products, and as a safer alternative to smoking tobacco for smokers and those around them.

It is also indicated in pregnant and lactating women making a quit attempt.

4.2. Posology and method of administration

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

Smoking/Vaping Cessation

Adults (over 18 years of age)

The patient should make every effort to stop smoking or vaping 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)/heavy vapers (e.g. vape frequently or use high strength e-liquid), 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/vaping with one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.

Most patients 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 or vaping 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)/ heavy vapers (e.g. vape frequently or use high strength e-liquid), two tablets per hour. Increasing to two tablets per hour may be considered for patients who fail to stop smoking/vaping with the one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.

Most patients 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/vaping, 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/Vaping Reduction

Adults (over 18 years of age)

Use this product between smoking/vaping episodes to manage the urge to smoke/vape, to prolong smoke/vape-free intervals and with the intention to reduce smoking/vaping as much as possible. If a reduction in number of cigarettes/e-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 patient 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/vaping cessation instructions above can be followed.

Adolescents (12 to 18 years)

Where adolescents are motivated to stop smoking/vaping abruptly, smoking/vaping cessation should be recommended. However, smoking/vaping reduction can be considered where adolescents are not ready or able to stop smoking/vaping 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/vaping reduction prior to stopping” regimen.

Use this product between smoking/vaping episodes, as needed to manage the urge to smoke/vape, to prolong smoke/vape-free intervals and to reduce their use as much as possible . If a reduction in number of cigarettes/e-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 patient 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/vaping cessation instructions for adolescents (12 to 18 years) given above can be followed.

4.3. Contraindications

Hypersensitivity to any component of the sublingual tablet.

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. The risks of continued vaping are not yet established.

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 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. The risks of continued vaping are not yet established.

Diabetes mellitus: Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when quitting 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 or vapers 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.

4.5. Interaction with other medicinal products and other forms of interaction

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.

4.6. Fertility, pregnancy and lactation

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 foetus 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.

Because of the potential for nicotine-free periods, intermittent dose forms are preferable as these usually provide a lower daily dose of nicotine than patches. However, patches may be considered as an alternative if the woman is suffering from nausea during pregnancy. If patches are used they should be removed before going to bed.

There is no or limited data regarding the effect of vaping in pregnancy.

Use of NRT by the pregnant smoker/vaper 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.

There is no or limited data regarding the effect of vaping in lactating women.

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

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.

There is no or limited data regarding the effect of vaping on fertility.

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, 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.

Effects of Vaping Cessation

The nicotine withdrawal effects of vaping cessation have not been established; however it is anticipated that many of the effects relating to nicotine withdrawal will be the same as those seen with tobacco smoking cessation.

Adverse Drug Reactions

This product may cause adverse reactions similar to those associated with nicotine given by other means, including smoking and vaping, 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 or vaping 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.

System Organ Class

Reported Adverse Event

Incidence

Infections and Infestations

Rhinitis

Common

Immune System

Hypersensitivitya

Common

Disorders

Anaphylactic reactiona

Not known

Psychiatric Disorders

Abnormal dreams*

Uncommon

Nervous System Disorders

Headachea#

Burning sensationc

Dizziness

Dysgeusia

Paraesthesiaa

Seizures

Very common

Common

Common

Common

Common

Not known

Eye Disorders

Blurred vision

Lacrimation increased

Not known

Not known

Cardiac Disorders

Palpitationsa

Tachycardiaa

Atrial fibrillation

Common

Uncommon

Very rare

Vascular Disorders

Flushinga

Hypertensiona

Uncommon

Uncommon

Respiratory, Thoracic and Mediastinal Disorders

Throat irritation**

Cough**

Sore mouth or throat

Bronchospasm

Dysphonia

Dyspnoeaa

Nasal congestion

Sneezing

Throat tightness

Very common

Common

Common

Uncommon

Uncommon

Uncommon

Uncommon

Uncommon

Uncommon

Gastrointestinal Disorders

Hiccups****

Nauseaa

Abdominal pain

Diarrhoea***

Dry mouth

Dyspesia

Flatulence

Salivary hypersecretion

Stomatitis

Vomitinga

Eructation

Glossitis

Oral mucosal blistering and exfoliation

Paraesthesia oral***

Dysphagia

Hypoaesthesia oral***

Retching

Dry throat

Gastrointestinal discomforta

Lip pain

Very common

Very common

Common

Common

Common

Common

Common

Common

Common

Common

Uncommon

Uncommon

Uncommon

Uncommon

Rare

Rare

Rare

Not known

Not known

Not known

Musculoskeletal and Connective Tissue Disorders

Pain in jawb

Muscle tightnessb

Uncommon

Not known

Skin and Subcutaneous Tissue Disorders

Hyperhidrosisa

Pruritusa

Rasha

Urticariaa

Erythemaa

Uncommon

Uncommon

Uncommon

Uncommon

Not known

General Disorders and Administration Site Conditions

Fatiguea

Astheniaa

Chest discomfort and paina

Malaisea

Allergic reactions including angioedema

Common

Unommon

Uncommon

Uncommon

Rare

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.

4.9. Overdose

Symptoms: Symptoms of overdose with nicotine from this product may occur in smokers/vapers who have previously had a low nicotine intake from cigarettes/e-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/vapers) is known to significantly increase tolerability compared with non- smokers/vapers. The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60 mg. 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/vapers 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.