Document: NiQuitin Clear transdermal patch ENG SmPC change

• NiQuitin Clear transdermal patch SmPC
• NiQuitin Clear transdermal patch ENG SmPC

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SUMMARY OF PRODUCT CHARACTERISTICS

NiQuitin Clear 7 mg/24 hours transdermal patch

NiQuitin Clear 14mg/24 hours transdermal patch

NiQuitin Clear 21mg/24 hours transdermal patch

Each (7 cm²) patch of 7 mg/24 hours contain 36 mg nicotine
Each (15cm²) patch of 14 mg/24 hours contain 78 mg nicotine
Each (21 cm²) patch of 21 mg/24 hours contain 114 mg nicotine

For thefull list of excipients, see section 6.1.

Transdermal patch.

21 mg/24 hours is marked NCQ 21

14 mg/24 hours is marked NCQ 14

7 mg/24 hours is marked NCQ 7

NiQuitin Clear is indicated for the relief of nicotine withdrawal symptoms associated with smoking cessation. If possible, when stopping smoking, NiQuitin Clear should be used in conjunction with a behavioural support programme.

The patches should be used as directed below. Prior to initiation of therapy users should be committed to stopping smoking. During a quit attempt, any smoking is very likely to lead to relapse. Therefore users must not smoke during a cessation attempt. No other form of nicotine should be taken at the same time.Concurrent behavioural support is recommended, as such programmes have been shown to be beneficial for smoking cessation.

Posology

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

Dose	Duration
Step 1 NiQuitin Clear 21 mg	First 6 weeks
Step 2 NiQuitin Clear 14 mg	Next 2 weeks
Step 3 NiQuitin Clear 7 mg	Last 2 weeks

Smokers with low nicotine dependence (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 NiQuitin Clear 7 mg for the final 2 weeks.

NiQuitin Clear patients on NiQuitin Clear 21 mg who experience excessive side-effects (please refer to section 4.4), which do not resolve within a few days, should change to NiQuitin Clear 14mg. This strength should then be continued for the remainder of the 6 week course before stepping down to NiQuitin Clear 7 mg 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 patients who have reduced strength as above), should be completed in full. It should not extend beyond 10 consecutive weeks.

However, further courses may be used at a later time, for NiQuitin Clear users who continue or resume smoking.

Paediatric population

NiQuitin Clear should only be used in adolescents (aged 12 – 17 years) with advice from a doctor.

NiQuitin Clear is not recommended for use in children under 12 years of age due to lack of data on safety and efficacy.

Method of administration

NiQuitin Clear patches should be applied once a day, at the same time each day and preferably soon after awakening, to a non-hairy, clean, dry skin site and worn continuously for 24 hours. The NiQuitin Clear 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 optimize the effect against morning cravings.

Hypersensitivity to the active substance or to any of the excipientslisted in section 6.1.

NiQuitin Clear patches should not be used by non-smokers, occasional smokers or children.

NiQuitin Clear should not be used in patients with recent myocardial infarction, unstable or worsening angina pectoris, Prinzmetal’s angina, severe cardiac arrythmias, or recent cerebrovascular accident.

Paediatric population

The amounts of nicotine that are tolerated by adult smokers can produce symptoms of poisoning and could prove fatal if NiQuitin Clear is applied by children, or ingested by children. Even used NiQuitin Clear patches contain enough residual nicotine to be harmful to children.

Patients should therefore be warned to keep patches out of the reach of children and instructed to dispose of used patches carefully in a place away from children.

Safety on Handling

NiQuitin Clear is potentially a dermal irritant and can cause contact sensitization. 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.

Precautions

Patients must stop smoking and using any other form of nicotine completely when starting and throughout NiQuitin Clear therapy. Patients should be warned that if they continue to smoke or use any additional source of nicotine while using NiQuitin Clear there is a potential to experience adverse effects due to peak nicotine levels higher than those experienced from smoking or using other nicotine products alone. If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the NiQuitin Clear dose should be reduced or discontinued. Concomitant medications may need dosage adjustment (see Drug Interactions).

The maximum duration of a treatment course is 10 weeks. Patients should not continue beyond this treatment period because the chronic consumption of nicotine can be toxic and addicting. Tachycardia occurring in association with the use of NiQuitin Clear was reported occasionally.

NiQuitin Clear should be used only with medical advice in patients with:

• cardiovascular disease (e.g. stable angina pectoris, heart failure, cerebrovascular disease, vasospastic diseases, severe peripheral vascular disease),

• uncontrolled hypertension, since nicotine may be a risk factor for the development of malignant hypertension,

• atopic or eczematous dermatitis (due to localised patch sensitivity)

• severe renal or hepatic impairment or active peptic ulcers,

• hyperthyroidism, pheochromocytoma or insulin-dependent diabetes.

• Seizures: use with caution in subjects taking anti-convulsant therapy or with a history of epilepsy as cases of convulsions have been reported in association with nicotine.

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 NiQuitin Clear and contact their physicians.

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

Smoking cessation, with or without nicotine substitutes, may alter the response to concomitant medication in ex-smokers.

The following drugs may require adjustment in dose at cessation of smoking.

May require a decrease in dose at cessation of smoking	Possible mechanism of action
Caffeine, theophylline, imipramine, pentazocine, phenacetin, phenylbutazone, tacrine, clomipramine.	Reduced induction of CYP1A2
Insulin	Increase in sub-cutaneous insulin absorption
Adrenergic blockers eg prazosin, propranolol.	Decreases circulating catecholamines
May require an increase in dose at cessation of smoking	Possible mechanism of action
Adrenergic agonists e.g. isoprenaline, salbutamol	Decreases in circulating catecholamines

Fertility

Effects on human fertility have not been established. Animal studies on fertility are considered to have limited relevance to the clinical use of transdermal nicotine, since the overall dose and routes of exposure cannot be directly correlated to the controlled use of a transdermal nicotine replacement therapy [refer 5.3 Preclinical Safety Data]

Pregnancy

Nicotine passes on to the foetus and affects the breathing pattern and circulation of the foetus. The effect on the circulation of the foetus is dose-dependent.

Pregnant smokers should therefore always be recommended to stop smoking without nicotine replacement therapy. The risk of continuous smoking may pose a greater risk for the foetus than the use of nicotine replacement therapy and medical assessment of the risk/benefit ratio of the use of NiQuitin Clear should be made. NiQuitin Clear should not be used by others than pregnant women with high nicotine dependence on doctors advice.

Breastfeeeding

Nicotine passes freely into breast milk in quantities that may affect the child even with therapeutic doses. NiQuitin Clear should therefore be avoided during breastfeeding. Shouldsmoking cessation not be achieved, use of NiQuitin Clear by breastfeeding mothers should only be initiated after advice from a healthcare professional.

NiQuitin Clear has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Application site reactions are the most frequent adverse reaction associated with NiQuitin Clear. NiQuitin Clear 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.

Cardiac disorders

Common (≥1/100, <1/10): palpitations

Uncommon (≥1/1000, <1/100): tachycardia NOS

Nervous system disorders

Very common (≥1/10): headache, dizziness

Common (≥1/100,<1/10: tremor)

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, diarrhoea NOS, dry mouth, constipation

Skin and subcutaneous tissue disorders

Common (≥1/100, <1/10): sweating increased

Very rare (<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

Immune system disorders

Uncommon (≥1/1000, <1/100): hypersensitivity NOS*

Frequency not known, cannot be estimated from available data: anaphylactic reactions

Psychiatric disorders

Very common (≥1/10): sleep disorders including abnormal dreams and insomnia

Common (≥1/100, <1/10): nervousness

*see below

Application site reactions, including transient rash, itching, burning, tingling, numbness, swelling, pain and urticaria are the most frequent undesirable effects of NiQuitin Clear 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 generalised skin reaction (e.g. urticaria, hives or generalised skin rashes) users should be instructed to discontinue use of NiQuitin Clear and contact their physician.

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

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 national reporting system listed in Appendix V

4.9 Overdose

The effects of applying several NiQuitin Clear patches simultaneously or swallowing NiQuitin patches are unknown.

Signs and symptoms of an overdose from a NiQuitin Clear patch would be expected to be the same as those of acute nicotine poisoning, including pallor, cold sweat, nausea, salivation, vomiting, abdominal pain, diarrhoea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion and weakness. Prostration, hypotension, respiratory failure and convulsions may ensue with large overdoses. Lethal doses produce convulsions quickly and death follows as a result of peripheral and central respiratory paralysis or, less frequently, cardiac failure.

Overdose from topical exposure

The NiQuitin patch should be removed immediately if the patient shows signs of overdosage and the patient should seek immediate medical care. 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 patch because of a depot of nicotine in the skin.

Overdose from ingestion

Activated charcoal should be administered as long as the patch remains in the gastrointestinal tract since it will continue to release nicotine for many hours.

Management of nicotine poisoning

Other supportive measures include diazepam or barbiturates for seizures, atropine for excessive bronchial secretions or diarrhoea, respiratory support for respiratory failure and vigorous fluid support for hypotension and cardiovascular collapse.

Pharmacotherapeutic group: Drugs used in nicotine dependence

ATC-code: N07BA01

Nicotine, the chief alkaloid in tobacco products, 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 liability, 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, nicotine withdrawal symptoms were alleviated as well as craving. The severity of cravings was reduced by at least 35% at all times of day during the first two weeks of abstinence, compared to placebo (p0.05).

Absorption

Following transdermal application, the skin rapidly absorbs nicotine released from the patch adhesive. The plasma concentrations of nicotine reach a plateau within 2-4 hours after initial application of NiQuitin Clear with relatively constant plasma concentrations persisting for 24 hours or until the patch is removed. The bioavailability of the nicotine released from the patch is approx. 70% and the remainder of the released nicotine evaporates from the edge of the patch.

With daily application of NiQuitin Clear (worn for 24 hours), steady state plasma nicotine concentrations are achieved following the second NiQuitin Clear application and are maintained throughout the day. Steady state maximum concentrations are approximately 30% higher than those following a single application of NiQuitin Clear.

Plasma concentrations of nicotine are proportional to dose for the three strenghts of NiQuitin Clear. 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 high nicotine plasma concentrations seen initially from smoking is not observed with NiQuitin Clear.

Distribution

Following removal of NiQuitin Clear, 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 NiQuitin Clear is removed most non-smoking patients will have non-detectable nicotine concentrations in 10 to 12 hours.

Less than 5% of nicotine is bound to plasma proteins, and 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. Nicotine can pass the blood –brain barrier.

Metabolism

Nicotine is mainly metabolised in the liver, and average plasma clearance is about 1.2 l/min; nicotine is also metabolised by thekidney and the lung. 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 elimination half-life of nicotine ranges from 1 to 2 hours and cotinine’s between 15 and 20 hours.

Elimination

Both nicotine and its metabolites are excreted through the kidneys. The amount of unmetabolised nicotine which is excreted is pH-dependent. At maximum flow and extreme urine acidification (pH<5) the amount can be as much as 30%, but normally the amount is about 10%.

Special patientgroups

There were no differences in nicotine kinetics between men and women using NiQuitin. Obese men using NiQuitin had significantly lower AUC and Cmax values compared with normal weight men. Nicotine kinetics were similar for all sites of application on the upper body and upper outer arm.

The general toxicity of nicotine is well documented. Nicotine was not mutagenic or carciogenic in conventional assays. In studies in pregnant animals, at exposure levels resulting in maternal toxicity (in excess of those that will be obtained with the recommended use of NiQuitin Clear), a mild foetal toxicity was seen. Other effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development. Effects on fertility have not been established.

Nicotine has been reported to induce changes to the ovary and uterus of female rats and mice following repeated oral or intraperitoneal administration of doses exceeding those that result from the recommended use of NiQuitin Clear. Repeated intraperitoneal or oral administration of nicotine to male rats at doses exceeding those resulting from the recommended use of NiQuitin Clear was reported to cause a decrease in testis weight, changes in the epididymis and vas deferens, and a reversible decrease in Sertoli cell numbers with impairment of spermatogenesis.

Not applicable.

3 years

Store below 30C

21 mg/24 hours 7, 14, 21, 28 or 42 patches
14 mg/24 hours 7 or 14 patches
7 mg/24 hours 7 or 14 patches

Each patch is rectangular and is comprised of a clear backing and a protective liner. Each patch is contained in a laminate sachet.

Not all pack sizes may be marketed.

No special requirements.

GlaxoSmithKline Consumer Healthcare A/S

Nykær 68

2605 Brøndby

Denmark

21 mg/24 hours: 16487
14 mg/24 hours: 16488
7 mg/24 hours: 16489

2002-05-31/2007-05-31

2015-09-15