4.1. Therapeutic indications

Nicorette Inhalator 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.

Nicorette Inhalator 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

Nicorette Inhalator should be used whenever the urge to smoke/vape is felt or to prevent cravings in situations where these are likely to occur.

Smokers/vapers willing or able to stop smoking/vaping immediately should initially replace all their cigarettes/e-cigarettes with the Inhalator and as soon as they are able, reduce the number of Inhalator cartridges used until they have stopped completely.

Smokers/vapers aiming to reduce cigarettes/e-cigarettes should use the Inhalator, as needed, between smoking/vaping episodes to prolong smoke/vape-free intervals and with the intention to reduce smoking/vaping as much as possible.

As soon as they are ready smokers/vapers should aim to quit smoking/vaping completely.

Maximum daily dose: 6 cartridges.

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

Each cartridge can be used for approximately eight 5-minute sessions, with each cartridge lasting approximately 40 minutes of intense use. The more the subject is able to use the Inhalator, the easier it will be to achieve maximum reduction of cigarettes/e-cigarettes and/or quit smoking/vaping completely.

Method of administration

The cartridge is inserted into the mouthpiece according to the instructions. When a patient draws air into the mouth through the mouthpiece, nicotine is vaporised and absorbed by the buccal mucosa. Minimal nicotine reaches the lungs. The amount of nicotine from a puff is less than that from a cigarette. To compensate for less nicotine delivery from a puff it is necessary to inhale more often than when smoking a cigarette.

The number of cartridges, frequency, puffing/inhalation time and technique does vary between individuals.

The actual time that the cartridge is active depends on the intensity of use. After about 40 minutes of intense use the maximal dose is achieved and it is about then that the nicotine amounts released from the cartridge begin to fall away, such that the cartridge is rejected by the user.

4.3. Contraindications

Hypersensitivity to any component of the Inhalator.

Nicorette Inhalator 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. 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. If a child swallows, chews or sucks on the Inhalator cartridge (used as well as unused) there is a risk of poisoning in the child.

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.

Lung Disease: Patients with obstructive lung disease may find use of the Inhalator difficult. Nicotine mouth spray, gum, patch, nasal spray or sublingual tablet may be preferred in such cases. This product should be used with caution in patients with chronic throat disease and bronchospastic disease.

Allergic reactions: Susceptibility to angioedema and urticaria.

Potential choking hazard: This product contains some small parts. Any unused cartridges should remain in the cartridge tray to minimise the risk of swallowing.

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

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. Nicotine passes to the foetus and affects its breathing movements and circulation. The effect on the circulation is dose-dependent. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the foetus 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 considered as an alternative if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the foetus would not normally be exposed to nicotine.

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. 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.

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 take 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 medicinal 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 use of Nicorette Inhalator by those who have not been in the habit of inhaling tobacco smoke/vaping could possibly lead to nausea, faintness or headaches.

Most of the undesirable effects reported by the patient occur during the first weeks after starting treatment. About 40% of users experience mild local reactions such as cough and irritation in the mouth and throat however most subjects adapt to this with ongoing use.

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

Immune System Disorders

Hypersensitivitya

Anaphylactic reactiona

Common

Not known

Psychiatric Disorders

Abnormal dreamsc

Uncommon

Nervous System Disorders

Headachea#

Burning sensation*

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

Uncommon

Uncommon

Very rare

Vascular Disorders

Flushinga

Hypertensiona

Uncommon

Uncommon

Respiratory, Thoracic and Mediastinal Disorders

Cough**

Throat irritation**

Nasal congestion

Bronchospasm

Dysphonia

Dyspnoeaa

Sneezing

Throat tightness

Common

Very common

Common

Uncommon

Uncommon

Uncommon

Uncommon

Uncommon

Gastrointestinal Disorders

Nauseaa

Stomatitis

Hiccups****

Abdominal pain

Diarrhoea***

Dry mouth

Dyspepsia

Flatulence

Salivary hypersecretion

Vomitinga

Eructation

Glossitis

Oral mucosal blistering and exfoliation

Paraesthesia oral***

Dysphagia

Hypoaesthesia oral***

Retching

Dry throat

Gastrointestinal discomforta

Lip pain

Very common

Very common

Very common

Common

Common

Common

Common

Common

Common

Common

Uncommon

Uncommon

Uncommon

Uncommon

Rare

Rare

Rare

Not known

Not known

Not known

Skin and Subcutaneous Tissue Disorders

Hyperhidrosisa

Pruritusa

Rasha

Urticariaa

Angioedemaa

Erythemaa

Uncommon

Uncommon

Uncommon

Uncommon

Not known

Not known

Musculoskeletal and Connective Tissue Disorders

Pain in Jawb

Muscle tightnessb

Uncommon

Not known

General Disorders and Administration Site Conditions

Fatiguea

Astheniaa

Chest discomfort and paina

Malaisea

Common

Uncommon

Uncommon

Uncommon

a Systemic effects; b Tightness of jaw and pain in jaw with nicotine gum formulation c Identified only for formulations applied during the night

* At the application site

**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 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 in-take 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.