NiQuitin Patch 21mg/24h - Smoking Cessation - 28 Patches

1. NAME OF THE MEDICINAL PRODUCT

NIQUITIN 21 mg/24 hours, transdermal device

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Nicotine ............................................................ 114.00 mg For one 22 cm2 transdermal device. For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Transparent transdermal device.

4. CLINICAL DATA

4.1 Therapeutic indications This medicinal product is indicated for the treatment of tobacco dependence in order to relieve nicotine withdrawal symptoms in subjects wishing to stop smoking. Although permanent cessation of smoking is preferred, this drug may be used in a smoking reduction strategy as a step towards permanent cessation. 4.2. 4.2. Dosage and administration Reserved for adults and children over 15 years of age. DOSAGE The degree of nicotine dependence will be assessed by the number of cigarettes consumed per day or by the Fagerström test. This medicine may be used as monotherapy or in combination with NIQUITIN 2 g chewing gum or NIQUITIN 2 mg chewable tablets. If used in combination, medical advice should be sought. - QUITTING TOBACCO o Monotherapy: Initial phase 3 to 4 weeks Follow-up treatment 3 to 4 weeks Withdrawal from treatment 3 to 4 weeks Fagerström test score of 5 or more or Smoking 20 or more cigarettes per day NIQUITIN 21 mg/24 h NIQUITIN 14 mg/24 h or NIQUITIN 21 mg/24 h* NIQUITIN 7 mg/24 h or NIQUITIN 14 mg/24 h then NIQUITIN 7 mg/24 h* Fagerström score less than 5 or Smoker of less than 20 cigarettes per day NIQUITIN 14 mg/24 h or increase to NIQUITIN 21 mg/24 h* NIQUITIN 14 mg/24 h or NIQUITIN 7 mg/24 h** NIQUITIN 7 mg/24 h or discontinue** *Depending on withdrawal symptom results. **If results are satisfactory. The dosage of the transdermal system should be adapted to the individual response: increase the dose if smoking abstinence is not complete or if withdrawal symptoms are observed, decrease in case of suspected overdose. The duration of treatment is approximately 3 months but may vary according to individual response. It is recommended not to use this drug beyond 6 months. - In combination with oral forms In combination with NIQUITIN 2 mg Gum or NIQUITIN 2 mg Chewable Tablets: Individuals who, in spite of well-managed monotherapy, continue to experience cravings to smoke, or individuals who have failed monotherapy, may combine the transdermal devices with an oral form that has a faster onset of withdrawal symptoms, such as NIQUITIN 2 mg Gum or NIQUITIN 2 mg Suckable Tablets. The combination of transdermal devices with chewing gums has been shown to be superior to either treatment alone. Initial Treatment Treatment should begin with a 21 mg/24 hr transdermal device applied to the skin daily in the morning and removed and replaced the following morning, in combination with NIQUITIN Chewing Gum 2 mg or NIQUITIN Chewable Tablet 2 mg. Chew one gum or suck one tablet each time the urge to smoke arises with a minimum of 4 NIQUITIN Gum or 4 NIQUITIN 2 mg tablets per day. Usually 5 or 6 gums or tablets provide adequate effect. Do not use more than 24 gums or 24 tablets per day. This full dose should be used for 6 to 12 weeks, after which a gradual withdrawal from substitutes should be initiated. This should be done in the following way: Use the lower dose transdermal devices, i.e. 14 mg/24 h for 3-6 weeks and then 7 mg/24 h for 3-6 weeks while continuing to use the same number of 2 mg chewing gum or 2 mg sucking tablet as at the start of treatment, and then reduce the number of 2 g chewing gum or 2 mg sucking tablet used per day, up to a maximum of 12 months of total treatment. See printable CPR table Gradually reduce the number of chewing gums or sucking tablets until cessation - PROGRESSIVE STOPPING o Monotherapy If the patient chooses to reduce before quitting, they can reduce gradually by starting treatment: - with a 21 mg/24 h device (if the patient has a score ≥ 5 on the Fagerström test) - or with a 14 mg/24 h device (if the patient has a score < 5 on the Fagerström test) Per day for 2 weeks, then stop smoking at the end of the 2 weeks and continue treatment at the dosage described in the printable PCR table In combination with oral forms Combination of transdermal device treatment with oral forms NIQUITIN 2 mg chewing gum or chewing tablet can be done once smoking has been stopped according to the dosage described above.The reduction in tobacco consumption should gradually lead the patient to stop smoking completely. This should be attempted as soon as possible within 6 months of starting treatment. If after 9 months of treatment, the attempt to stop smoking completely has failed, it is recommended that advice be sought from a health professional to consider an alternative strategy. It is recommended to apply the device after opening to a dry skin surface without skin lesions and where hairiness is scarce (trunk, upper arm). Do not apply to red, damaged or irritated skin. A new system should be applied every 24 hours to a different application site, preferably in the morning upon awakening. The device should be kept in its protective pouch until use. During handling, avoid contact with the eyes, nose and wash hands after application. 4.3. Contraindications - Non-smoker or occasional smoker. - Hypersensitivity to any of the ingredients. - Skin condition that may interfere with the use of a transdermal device. 4.4. Special warnings and precautions for use Special warnings - To ensure the best chance of success, the use of this medicine should be accompanied by a complete cessation of smoking. - Due to the pharmacological effects of nicotine, certain medical conditions require medical advice and supervision: o severe liver and/or kidney failure, o developing gastric or duodenal ulcers, - Nicotine is a toxic substance. In children, the application of this medicine can be fatal, so do not leave this device within the reach of children even after use. It is recommended to fold the transdermal device on itself before throwing it away. Special precautions for use In case of burning, stinging, itching, skin rash, during sun exposure, it is recommended to stop the treatment temporarily until the symptoms disappear. In case of severe or persistent skin reaction, it is recommended to discontinue the treatment and to use another pharmaceutical form (see section 4.8). 4.5. Interactions with other medicinal products and other forms of interaction Tobacco may, through a process of enzymatic induction due to aromatic hydrocarbons, decrease the blood concentrations of certain medicinal products such as caffeine, theophylline, imipraminic antidepressants, flecainide, pentazocine. Smoking cessation, especially when taking this drug, may lead to an increase in the concentrations of these active ingredients due to the reversibility of the enzymatic induction effect. For drugs with a narrow therapeutic margin, such as theophylline, smoking cessation should be accompanied, in addition to dosage adjustment, by close clinical and even biological monitoring, with the patient being informed of the risks of overdose. Because of its specific pharmacological, cardiovascular, neurological and endocrine properties, nicotine may, like tobacco: - lead to an increase in cortisol and cathecolamine concentrations, - require dosage adjustment of nifedipine, beta-blockers and insulin, - reduce the effects of diuretics, - slow the rate of healing of gastric ulcers by H2 antihistamines, - increase the incidence of adverse effects of estrogestogens 4.6. Pregnancy and lactation Pregnancy 1/ Experimental studies in several species have not shown any teratogenic or foetotoxic effect of nicotine administered at continuous flow and at maternotoxic doses. Under the same conditions of administration, fetal hypotrophy is observed at even higher doses in one species, the mouse, but not in the rat or rabbit. In the clinic, a limited number of observations have not yet been made showing any deleterious effects, either maternal or foetal, of nicotine used for smoking cessation. 4.7. Effects on ability to drive and use machines Not applicable. 4.8. Adverse reactions Nicotine transdermal devices may cause adverse reactions similar to nicotine administered by other means. Systemic side effects - palpitations - dizziness, headache, - nausea, vomiting, - insomnia, dreaming disorder Local side effects - erythema and pruritus at the application site, more rarely oedema, burning sensation. These effects are mostly moderate and regress spontaneously after removal of the system. In case of severe or persistent skin reactions, it is recommended to stop the treatment and use another form of nicotine substitute. Some symptoms such as dizziness, headache and insomnia may be related to smoking cessation. An increase in the occurrence of mouth ulcers may occur after smoking cessation. The causal relationship is not clearly established. 4.9. Overdose Nicotine overdose may occur if the treated patient had previously very low nicotine intakes or is concomitantly using other nicotine-based smoking cessation treatments. Symptoms of overdose are those of acute nicotine intoxication including nausea, hyper salivation, abdominal pain, diarrhoea, sweating, headache, dizziness, hearing impairment and general weakness. At high doses, hypotension, weak and irregular pulse, respiratory distress, prostration, cardiovascular collapse and convulsions may occur. The doses of nicotine tolerated by smokers during treatment may lead to acute intoxication which may be fatal in young children. Action in case of overdose: Nicotine should be discontinued immediately and symptomatic treatment instituted. Assisted ventilation and oxygen therapy should be undertaken if necessary.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties DRUGS USED IN NICOTINE DEPENDENCE, ATC Code: N07BA01 Abrupt cessation of smoking after prolonged daily use results in a withdrawal syndrome comprising at least four of the following symptoms: dysphoria or depressed mood, insomnia, irritability, feelings of frustration or anger, anxiety, difficulty in concentrating, restlessness or impatience, slowing of heart rate, increased appetite, increased weight. The sensation of craving for nicotine is considered to be a clinical symptom in its own right of the withdrawal syndrome. Clinical studies have shown that nicotine replacement products can help smokers to abstain from smoking or to reduce their tobacco consumption by reducing withdrawal symptoms. The adverse effects of continued smoking in patients with coronary artery disease and/or a history of stroke have been clearly demonstrated. Studies in these patients have shown that there is no deleterious effect of nicotine replacement therapy. 5.2. Pharmacokinetic properties Nicotine is absorbed directly through the skin into the systemic circulation. Plasma concentrations of nicotine reach a plateau within 2-4 hours after application of the transdermal system. A relatively constant plasma concentration persists for 24 hours. After repeated daily application of NIQUITIN, equilibrium is achieved on the second application with dose-dependent concentrations maintained throughout the day. Plasma nicotine concentrations are dose-dependent for all three NIQUITIN dosages. After repeated application of NIQUITIN 22, 15 or 7 cm2, the mean maximum steady-state plasma nicotine concentrations are approximately 17 ng/ml, 12 ng/ml, 6 ng/ml respectively. For comparison, smoking a cigarette every half hour leads to mean plasma concentrations of about 44 ng/ml. The sharp and early peak in blood nicotine levels observed with cigarette smoking is not observed with NIQUITIN. After withdrawal from the system, plasma nicotine concentrations are slower to decrease than would be expected from the plasma elimination half-life of nicotine, determined after intravenous administration, which is 2 hours. The probable existence of skin deposition explains why about 10% of the nicotine reaching the bloodstream comes from the skin after withdrawal from the system. The volume of distribution of nicotine is large (about 2.5 l/kg). Nicotine crosses the blood-brain barrier, the placenta and is found in breast milk. Plasma protein binding is negligible.

6. PHARMACEUTICAL DATA

6.1. List of excipients Ethylene/vinyl acetate copolymer (40% VA). Occlusive carrier: Ethylene, vinyl acetate, polyethylene terephthalate. Flow control membrane: Polyethylene film. Contact adhesive: Polyisobutylene. Release liner: Silicone polyester film 6.2. Incompatibilities Not applicable. 6.3. Shelf life 2 years. 6.4. Special storage conditions Store at a temperature not exceeding +25°C. 6.5. Nature and contents of packaging Transdermal device in a bag (PET/PE/Aluminium/acrylonitrile polymer). Box of 7, 14 or 28. 6.6. Special precautions for disposal and handling No special requirements.

7. MARKETING AUTHORISATION HOLDER

Laboratoires GLAXOSMITHKLINE SANTE GRAND PUBLIC 100, route de Versailles BP 23 78164 Marly-Le-Roi Cedex

8. MARKETING AUTHORISATION NUMBER(S)

- 379 559-5 or 34009 379 559 5 9: transdermal device in sachet (PET/PE/Aluminium/Acrylonitrile Copolymer); box of 28. 9. DATE OF FIRST AUTHORISATION/REINVAL OF AUTHORISATION [to be completed by the holder] 10. DATE OF UPDATE OF TEXT [to be completed by the holder] 11. DOSIMETRY Not applicable. INSTRUCTIONS FOR THE PREPARATION OF RADIOPHARMACEUTICALS Not applicable. CONDITIONS OF PRESCRIPTION AND DELIVERY Medicinal product not subject to medical prescription.