Document: spc-doc_PL 02855-0279 change

• spc-doc_PL 00079-0361
• spc-doc_PL 02855-0279

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

NICABATE CLEAR 21 mg/24 hrs transdermal patches

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

NICABATE CLEAR is a transdermal delivery system for transdermal use available in systems of 22 cm containing 114 mg nicotine, equivalent to

5.1 mg/cm of nicotine and delivers 21 mg over 24 hours.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Transdermal patch.

Each patch is rectangular and is comprised of clear backing and a protective liner which is removed prior to use.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

NICABATE CLEAR is indicated for the relief of nicotine withdrawal symptoms including cravings as an aid to smoking cessation. If possible, when stopping smoking, NICABATE CLEAR should be used in conjunction with a behavioural support programme.

NICABATE CLEAR is indicated in adults and adolescents aged 12 years and over.

4.2 Posology and method of administration

Posology

Adults (18 years and over)

The patches should be used as directed below. Prior to initiation of therapy users should be committed to stopping smoking. During a quit attempt, every effort should be made to stop smoking during treatment with NICABATE CLEAR. Concurrent behavioural support is recommended, as such programmes have been shown to be beneficial for smoking cessation.

NICABATE CLEAR patches should be applied once a day, at the same time each day and preferably soon after waking and worn continuously for 24 hours.

NICABATE CLEAR therapy should usually begin with NICABATE CLEAR 21 mg/24 hrs and be reduced according to the following dosing schedule:-

Dose		Duration
Step	NICABATE CLEAR 21	First 6
1	mg/24 hrs	weeks
Step	NICABATE CLEAR 14	Next 2
2	mg/24 hrs	weeks
Step	NICABATE CLEAR 7	Last 2
3	mg/24 hrs	weeks

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 NICABATE CLEAR 7 mg/24 hrs for the final 2 weeks.

Patients on NICABATE CLEAR 21 mg/24 hrs who experience excessive side effects, which do not resolve within a few days, should change to NICABATE CLEAR 14 mg/24 hrs. This strength should then be continued for the remainder of the 6 week course before stepping down to NICABATE CLEAR 7 mg/24 hrs 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 NICABATE CLEAR patch may be continued beyond 10 weeks if needed to stay cigarette free, however, those who use the patches beyond 9 months are recommended to seek additional help and advice from a healthcare professional.

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

Paediatric population

Adolescents (12 to 17 years) should follow the schedule of treatment for adults presented above for steps 1, 2 and 3, but as data are limited, duration of NRT in this age group is restricted to 12 weeks. If longer treatment is required advice from a healthcare professional should be sought.

NICABATE CLEAR is contraindicated in children under 12 years of age.

Method of administration

NICABATE CLEAR patches should be applied to a non-hairy, clean, dry skin site. The NICABATE 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 optimise the effect against morning cravings.

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.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

NICABATE CLEAR patches should not be used by:

•    children under 12 years

•    occasional smokers

•    non-smokers.

4.4 Special warnings and precautions for use

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, NICABATE CLEAR 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 NICABATE CLEAR 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.

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: NICABATE CLEAR is potentially a dermal irritant and can cause contact sensitisation.

4.5 Interaction with other medicinal products and other forms of interaction

No clinically relevant interactions between nicotine replacement therapy and other drugs has definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.

Healthcare professionals are reminded that smoking cessation itself may require the adjustment of some drug therapy.

4.6 Fertility, Pregnancy and lactation

Pregnancy

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. However for women unable to quit on their own, NRT may be recommended by a healthcare professional to assist a quit attempt. The risk of using NRT to the fetus 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.

However, as nicotine passes to the fetus affecting breathing movements and has a dose dependent effect on placental/fetal circulation, the decision to use NRT should be made as early on in the pregnancy as possible. The aim should be to use NRT for only 2-3 months.

Intermittent dosing products may be preferable as these usually provide a lower daily dose of nicotine than patches. However patches may be preferred if the woman is suffering from nausea during pregnancy. If patches are used they should be removed before going to bed.

Breast-feeding

Nicotine from smoking and NRT is found in breast milk. However the amount of nicotine the infant is exposed to from NRT 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.

Fertility

There are no relevant data available See section 5.3

4.7 Effects on ability to drive and use machines

NICABATE CLEAR transdermal patch has no or negligible influence on the ability to drive and use machines. However, users of nicotine replacement products should be aware that smoking cessation can cause behavioural changes.

4.8 Undesirable effects

Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1,000 to <1/100), rare (>1/10,000 to <1/1,000) and very rare (<1/10,000), not known (cannot be estimated from the available data).

Application site reactions are the most frequent adverse events associated with NICABATE CLEAR patches. Other adverse events may occur and may be related to the pharmacological effects of nicotine or withdrawal effects related to stopping smoking (see Pharmacodynamic Effects).

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.

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

System Organ Class and Frequency	Adverse Reaction/Event
Immune System Disorders Uncommon Very rare	hypersensitivity* anaphylactic reactions
Psychiatric Very common Common	sleep disorders including abnormal dreams and insomnia nervousness
Nervous system disorders Very Common	headache, dizziness
Common	tremor
Cardiac Disorders Common	palpitations
Uncommon	tachycardia
Respiratory, Thoracic and Mediastinal Disorders Common	dyspnoea, pharyngitis, cough
Gastrointestinal Disorders Very Common	nausea, vomiting
Common	dyspepsia, upper abdominal pain, diarrhoea, dry mouth, constipation
Skin and Subcutaneous Tissue Disorders Common Very rare	increased sweating allergic dermatitis *, contact dermatitis *, photosensitivity
Musculoskeletal and Connective Tissue Disorders Common	arthralgia, myalgia
General Disorders and Administration Site Conditions Very common Common	application site reactions* chest pain*, pain in limb*, pain, asthenia,

System Organ Class and Frequency	Adverse Reaction/Event
Uncommon	fatigue/malaise influenza-like illness

* The majority of 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.

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

Paediatric population (12-17 years inclusive)

There are no specific adverse event data for this population. However, the frequency, type and severity of adverse reactions in adolescents are expected to be the same as adults, based upon a pharmacokinetic study demonstrating a similar pharmacokinetic profile in the adolescent age group compared to adults.

4.9 Overdose

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in nicotine dependence

ATC code: N07BA01 Mechanism of action

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.

Clinical efficacy and safety

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

5.2 Pharmacokinetic properties

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

Plasma concentrations of nicotine are proportional to dose for the three dosage forms of NICABATE 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 pronounced early peak in nicotine blood levels seen with inhalation of cigarette smoke is not observed with NICABATE CLEAR.

Distribution

Following removal of NICABATE 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 NICABATE CLEAR is removed most non-smoking patients will have nondetectable nicotine concentrations in 10 to 12 hours.

A dose of radio-labelled 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.

Biotransformation

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.

Elimination

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 nicotine patches. Obese men using nicotine patch had significantly lower AUC and C_max 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.

5.3 Preclinical safety data

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 NICABATE CLEAR. Effects on fertility have not been established.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Drug Reservoir:

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

3 years

6.4    Special precautions for storage

Store below 30°C

6.5    Nature and contents of container

Each patch is contained in a laminate sachet.

7, 14, 21, 28 or 42 patches in a carton. Not all pack sizes may be marketed.

6.6    Special precautions for disposal

Nicotine residues in the used patches are a hazard to children and pets. Used patches should be folded, sticky sides together, put back in the empty sachet and disposed of in accordance with local requirements.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

Omega Pharma Ltd.

1^st Floor

32 Vauxhall Bridge Road LONDON, SW1V 2SA United Kingdom

MARKETING AUTHORISATION NUMBER(S)

PL 02855/0279

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:    03/04/2001

Date of latest renewal:    02/04/2006

DATE OF REVISION OF THE TEXT

16/12/2015