никоретте

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 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

The minimum lethal dose of nicotine in a non tolerant man has been estimated to be 40 to 60 mg. Even small quantities of nicotine may be dangerous in children and may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.

Symptoms

Signs and symptoms of an overdose from a nicotine patch would be expected to be the same as those of acute nicotine poisoning, including pallor, cold sweat, salivation, nausea, vomiting, abdominal pain, diarrhoea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion and weakness. Prostration, hypotension, respiratory failure, rapid or weak or irregular pulse, circulatory collapse and convulsions (including terminal convulsions) may ensue with large overdoses.

Management

Overdose from Topical Exposure

The nicotine patch(es) should be removed immediately in the event of an overdose or if the patient shows signs of overdosage. The user should seek medical attention immediately. The skin surface may be flushed with water and dried. No soap should be used since it may increase nicotine absorption. Nicotine will continue to be delivered into the bloodstream for several hours after removal of the system because of a depot of nicotine in the skin.

Overdose from Ingestion

All nicotine intake should stop immediately. The patient should seek medical attention immediately and be treated symptomatically.

Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastrointestinal absorption of nicotine.

Contraindications

Hypersensitivity to any component of the inhalator.

Никоретте Inhalator is contraindicated in children under the age of 12 years.

Никоретте is contraindicated in patients with hypersensitivity to the system, the active substance, or any of the excipients.

Никоретте patches should not be used by non-smokers, occasional smokers or children under 12 years.

Incompatibilities

Not applicable

Not applicable.

Pharmaceutical form

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. Excessive use of Никоретте Inhalator 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 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.

Allergic reactions (including symptoms of anaphylaxis) occur rarely during 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.

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

# 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.

Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, sleep disturbance, coughing or influenza-like illness. Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration and insomnia may be related to withdrawal symptoms associated with smoking cessation.

Application site reactions are the most frequent adverse reaction associated with Никоретте. Никоретте can cause other adverse reactions related to the pharmacological effect of nicotine or withdrawal effects related to smoking.

The following undesirable effects have been reported in clinical trials or spontaneously post-marketing.

Certain symptoms which have been reported such as depression, irritability, nervousness, restlessness, mood lability, anxiety, drowsiness, impaired concentration, insomnia and sleep disturbances may be related to withdrawal symptoms associated with smoking cessation. Subjects quitting smoking by any means could expect to suffer from asthenia, headache, dizziness, coughing or influenza-like illness.

Immune System Disorders

Uncommon>1/1000; <1/100: hypersensitivity NOS*

Very rare <1/10000: anaphylactic reactions

Psychiatric

Very common >1/10: sleep disorders including abnormal dreams and insomnia

Common >1/100; <1/10: nervousness

Nervous system disorders

Very Common >1/10: headache, dizziness

Common >1/100; <1/10: tremor

Not known: seizures

Cardiac disorders

Common >1/100; <1/10: palpitations

Uncommon >1/1000; <1/100: tachycardia NOS

Respiratory, Thoracic and Mediastinal Disorders

Common >1/100; <1/10: dyspnoea, pharyngitis, cough

Gastrointestinal Disorders

Very Common >1/10: nausea, vomiting

Common >1/100; <1/10: dyspepsia, abdominal pain upper, diarrhea NOS, dry mouth, constipation

Skin and Subcutaneous Tissue Disorders

Common >1/100; <1/10: sweating increased

Very rare > 1/100000; <1/10000: dermatitis allergic*, dermatitis contact*, photosensitivity

Musculoskeletal and Connective Tissue Disorders

Common >1/100; <1/10: arthralgia, myalgia

General Disorders and Administration Site Conditions

Very Common >1/10: application site reactions NOS*

Common >1/100; <1/10: chest pain, pain in limb, pain NOS, asthenia, fatigue

Uncommon >1/1000; <1/100 malaise, influenza-like illness

* see below

Application site reactions, including transient rash, itching, burning, tingling, numbness, swelling, pain and urticaria are the most frequent undesirable effects of Никоретте patch. The majority of these topical reactions are minor and resolve quickly following removal of the patch. Pain or sensation of heaviness in the limb or area around which the patch is applied (e.g. chest) may be reported.

Hypersensitivity reactions, including contact dermatitis and allergic dermatitis have also been reported. In the case of severe or persistent local reactions at the application site (e.g. severe erythema, pruritus or oedema) or a generalized skin reaction (e.g. urticaria, hives or generalised skin rashes) users should be instructed to discontinue use of Никоретте and contact their physician.

If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the Никоретте dose should be reduced or discontinued.

Preclinical safety data

None stated.

The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and consequential mild fetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.

Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of Никоретте. Effects on fertility have not been established.

Comparison of the systemic exposure necessary to elicit these adverse responses from preclinical test systems with that associated with the recommended use of Никоретте indicate that the potential risk is low and outweighed by the demonstrable benefit of nicotine therapy in smoking cessation. However, Никоретте should only be used by pregnant women on medical advice if other forms of treatment have failed.

Therapeutic indications

Никоретте Inhalator 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.

Никоретте Inhalator is indicated in pregnant and lactating women making a quit attempt.

Никоретте patches relieve and/or prevent craving and nicotine withdrawal symptoms associated with tobacco dependence. They are 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.

Никоретте patches are indicated in pregnant and lactating women making a quit attempt.

If possible, when stopping smoking, Никоретте patches should be used in conjunction with a behavioural support programme.

Pharmacotherapeutic group

Pharmacodynamic properties

Pharmacotherapeutic Group: Drug for treatment of addiction.

ATC Code: N07B A01

Никоретте Inhalator facilitates uptake of nicotine through the buccal mucosa into the venous circulation. The amount taken up alleviates the craving symptoms caused by the absence of nicotine from smoking.

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

Pharmacotherapeutic classification: N07B A01

(Anti-smoking agents: N07BA, Nicotine 01)

Nicotine, the chief alkaloid in tobacco products and a naturally occurring autonomic drug, is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects.

Withdrawal from nicotine in addicted individuals is characterised by craving, nervousness, restlessness, irritability, mood lability, anxiety, drowsiness, sleep disturbances, impaired concentration, increased appetite, minor somatic complaints (headache, myalgia, constipation, fatigue) and weight gain.

Withdrawal symptoms, such as cigarette craving, may be controlled in some individuals by steady-state plasma levels lower than those for smoking.

In clinically controlled trials, Никоретте was shown to alleviate nicotine withdrawal symptoms as well as craving. Никоретте reduced the severity of cravings by at least 35% at all times of day during the first two weeks of abstinence, compared to placebo (p<0.05).

Pharmacokinetic properties

The following information is based on data derived from Никоретте 10mg Inhalator:

Nicotine given i.v. has a volume of the distribution of 2 or 3 l/kg with a half life of 1-2 hours. Average plasma clearance is about 1-2 l/min mainly in the liver. More than 20 metabolites are known, all less active than nicotine: cotinine, with a half life of 15-20 hours and concentrations ten times that of nicotine is the main one.

Plasma binding of nicotine below 5% means significant displacement of drugs or nicotine is unlikely. Nicotine is excreted in the urine principally as cotinine (15%), 3-hydroxycotinine (45%), nicotine (10%).

Most inhaled nicotine is absorbed via the buccal mucosa. Forced rapid inhalation over 20 minutes, results in a wide range of nicotine doses (1.3-6.2 mg). On average 2 mg of nicotine is released during 20 minutes of intensive use. Uptake is slow and free of the peaks resultant from cigarette smoking. In normal use, plasma levels of 6-8ng/ml nicotine are obtained - about one third that from smoking, which is equivalent to an hourly 2mg nicotine chewing gum.

When used like a cigarette the inhalator on average delivers 1mg in 80 puffs (e.g. 8 puffs per minute for 10 minutes). When used in this way this results in, a degree of nicotine substitution of about 50% compared to hourly smoking. Peak plasma levels occur within 15 minutes after the end of inhalation. Forced rapid inhalation for 20 minutes per hour for 12 hours achieved steady state plasma levels of 20-25ng/ml.

Ambient temperature affects volatilisation of nicotine, the biologically available dose rising by 35% for each 10°C above 20°C. Use below 15°C is not recommended.

Because the pattern of use if decided by the patient up to a limit of 6 cartridges per day to relieve craving, therapeutic levels of nicotine are individual, dictated by the level of dependence.

Absorption

Following transdermal application, the skin rapidly absorbs nicotine released initially from the patch adhesive. The plasma concentrations of nicotine reach a plateau within 2-4 hours after initial application of Никоретте with relatively constant plasma concentrations persisting for 24 hours or until the patch is removed. Approximately 68% of the nicotine released from the patch enters systemic circulation and the remainder of the released nicotine is lost via vaporisation from the edge of the patch.

With continuous daily application of Никоретте (worn for 24 hours), dose- dependent steady state plasma nicotine concentrations are achieved following the second Никоретте application and are maintained throughout the day. These steady state maximum concentrations are approximately 30% higher than those following a single application of Никоретте.

Plasma concentrations of nicotine are proportional to dose for the three dosage forms of Никоретте. The mean plasma steady state concentrations of nicotine are approximately 17 ng/ml for the 21 mg/day patch, 12 ng/ml for the 14 mg/day patch and 6 ng/ml for the 7 mg/day patch. For comparison, half-hourly smoking of cigarettes produces average plasma concentrations of approximately 44 ng/ml.

The pronounced early peak in nicotine blood levels seen with inhalation of cigarette smoke is not observed with Никоретте.

Distribution

Following removal of Никоретте, plasma nicotine concentrations decline with an apparent mean half-life of 3 hours, compared with 2 hours for IV administration due to continued absorption of nicotine from the skin depot. If Никоретте is removed most non-smoking patients will have non-detectable nicotine concentrations in 10 to 12 hours.

A dose of radiolabelled nicotine given intravenously showed a distribution of radioactivity corresponding to the blood supply with no organ selectively taking up nicotine. The volume of distribution of nicotine is approximately 2.5 l/kg.

Metabolism

The major elimination organ is the liver and average plasma clearance is about 1.2 l/min; the kidney and the lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be pharmacologically inactive. The principal metabolites are cotinine and trans- 3-hydroxycotinine. Steady state plasma cotinine concentrations exceed nicotine by 10-fold. The half-life of nicotine ranges from 1 to 2 hours and cotinine's between 15 and 20 hours.

Excretion

Both nicotine and its metabolites are excreted through the kidneys and about 10% of nicotine is excreted unchanged in the urine. As much as 30% may be excreted in the urine with maximum flow rates and extreme urine acidification (pH≤5).

There were no differences in nicotine kinetics between men and women using Никоретте. Obese men using Никоретте had significantly lower AUC and Cmax values compared with normal weight men. Linear regression of AUC vs total body weight showed the expected inverse relationship (AUC decreases as weight increases). Nicotine kinetics were similar for all sites of application on the upper body and upper outer arm.

Qualitative and quantitative composition

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 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 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. If a child swallows, chews or sucks on the nicotine 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 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.

The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.

Patients hospitalised for MI, severe dysrhythmia or CVA who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, Никоретте patches may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. Once patients are discharged from hospital they can use NRT as normal. If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the nicotine patch dose should be reduced or discontinued.

Diabetes: Blood glucose levels may be more variable when stopping smoking, with or without NRT as catecholamines released by nicotine can affect carbohydrate metabolism, so it is important for diabetics to monitor their blood glucose levels more closely than usual while using this product.

Allergic reactions: Susceptibility to angioedema and urticaria.

Atopic or eczematous dermatitis (due to localised patch sensitivity): In the case of severe or persistent local reactions at the site of application (e.g. severe erythema, pruritus or oedema) or a generalised skin reaction (e.g. urticaria, hives or generalised skin rashes), users should be instructed to discontinue use of Никоретте and contact their physician.

Contact sensitisation: Patients with contact sensitisation should be cautioned that a serious reaction could occur from exposure to other nicotine-containing products or smoking.

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

- Renal and hepatic impairment: Use 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.

- Phaeochromocytoma and uncontrolled hyperthyroidism: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.

- Seizures: Potential risks and benefits of nicotine should be carefully evaluated before use in subjects taking anti-convulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

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. The patches should be folded in half with the adhesive side innermost and disposed of with care.

Stopping smoking: Polycyclic aromatic hydrocarbons in tobacco smoke induce the metabolism of drugs catalysed by CYP 1A2 (and possibly by CYP 1A1). When a smoker stops this may result in a slower metabolism and a consequent rise in blood levels of such drugs.

Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.

Safety on handling: Никоретте is potentially a dermal irritant and can cause contact sensitisation. Care should be taken during handling and in particular contact with the eyes and nose avoided. After handling, wash hands with water alone as soap may increase nicotine absorption.

Effects on ability to drive and use machines

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

Not applicable.

Dosage (Posology) and method of administration

Adults and Children over 12 years of age

Никоретте Inhalator 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 Inhalator and as soon as they are able, reduce the number of cartridges used until they have stopped completely.

Smokers aiming to reduce cigarettes should use the Inhalator, 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: 6 cartridges.

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 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 and/or quit smoking 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.

Никоретте patches should be applied once a day, at the same time each day and preferably soon after waking, to a non-hairy, clean, dry skin site and worn continuously for 24 hours. The Никоретте patch should be applied promptly on removal from its protective sachet.

Avoid applying to any skin which is broken, red or irritated. After 24 hours the used patch should be removed and a new patch applied to a fresh skin site. The patch should not be left on for longer than 24 hours. Skin sites should not be reused for at least seven days. Only one patch should be worn at a time.

Patches may be removed before going to bed if desired. However use for 24 hours is recommended to optimise the effect against morning cravings.

Concurrent behavioural support is recommended, as such programmes have been shown to be beneficial for smoking cessation.

Adults 18 years and over

Abrupt cessation of smoking:

During a quit attempt every effort should be made to stop smoking with Никоретте patches.

Никоретте therapy should usually begin with Никоретте 21 mg and be reduced according to the following dosing schedule:-

Light smokers (e.g. those who smoke less than 10 cigarettes per day) are recommended to start at Step 2 (14 mg) for 6 weeks and decrease the dose to Никоретте 7 mg for the final 2 weeks.

Patients on Никоретте 21 mg who experience excessive side-effects (please refer to precautions), which do not resolve within a few days, should change to Никоретте 14mg. This strength should then be continued for the remainder of the 6 week course before stepping down to Никоретте 7mg for two weeks. If the symptoms persist the patient should be advised to seek the advice of a healthcare professional.

For optimum results, the 10 week treatment course (8 weeks for light smokers or patients who have reduced strength as above), should be completed in full. Treatment with Никоретте patch may be continued beyond 10 weeks if needed to stay cigarette free, however, those who have quit smoking but are having difficulty discontinuing using the patches recommended to seek additional help and advice from a healthcare professional.

Further courses may be used at a later time, for Никоретте patch users who continue or resume smoking.

Gradual Cessation:

For smokers who are unwilling or unable to quit abruptly.

The 21 mg patch can be used daily for 2-4 weeks while the user continues to smoke as needed. At the end of the 2-4 weeks the user should quit completely and continue using Step 1 21 mg patch for 6 weeks daily without smoking. Thereafter following the Step 2 and 3 directions for abrupt cessation above. Should the patient feel able to quit completely before their designated quit date they can do so.

Reduction in smoking:

For smokers who wish to cut down with no immediate plans to quit.

A patch can be used while the user continues to smoke as needed. The user should reduce the number of cigarettes smoked as far as possible and to refrain from smoking as long as possible. Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use the patches on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Temporary Abstinence

Apply a patch to control troublesome withdrawal symptoms including craving during the period when smoking is being avoided. Users should be encouraged to stop smoking completely as soon as possible.

If users are still feeling the need to use the patches on a regular basis 6 months after the start of treatment and have still been unable to undertake a permanent quit attempt, then it is recommended to seek additional help and advice from a healthcare professional.

Adolescents and children

Adolescents (12 to 17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above. Where adolescents are not ready or not able to stop smoking abruptly, advice from a healthcare professional should be sought.

Safety and effectiveness in children who smoke has not been evaluated. Никоретте is not recommended for use in children under 12 years of age.

Special precautions for disposal and other handling

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

Because of residual nicotine, used cartridges may be a hazard to children, animals and fish and so should never be thrown away or left lying around. They should be kept in the case and disposed of with household rubbish.

No special requirements.