Nicorette invisi 15 mg patch.

'Each patch is 13.5 sq.cm, containing nicotine 1.75mg/sq.cm, releasing a nominal 15 mg of nicotine per 16 hours'.

For a full list of excipients, see section 6.1.

Transdermal patch.

Semi-transparent, beige, imprinted 13.5 cm² rectangular TTS with rounded corners. Centrally located on a rectangular, aluminized and siliconised release liner'.

Nicorette Patch is indicated for the relief of nicotine withdrawal symptoms as an aid to smoking cessation in adults and children over 12 years of age.

If possible, Nicorette Patch should be used in conjunction with a behavioural support programme.

The patient should make every effort to stop smoking completely during treatment with Nicorette Patch.

Behavioural therapy, advice and support will normally improve the success rate.

It is intended that the patch is worn through the waking hours (approximately 16 hours) being applied on waking and removed at bedtime.

Adults (over 18 years of age)

For best results, most smokers are recommended to start on 25 mg / 16 hours patch (Step 1) and use one patch daily for 8 weeks. Gradual weaning from the patch should then be initiated. One 15 mg/16 hours patch (Step 2) should be used daily for 2 weeks followed by one 10 mg/16 hours patch (Step 3) daily for 2 weeks.

Lighter smokers (i.e. those who smoke less than 10 cigarettes per day) are recommended to start at Step 2 (15 mg) for 8 weeks and decrease the dose to 10 mg for the final 4 weeks.

Those who experience excessive side effects with the 25 mg / 16 hours patch (Step 1), which do not resolve within a few days, should change to a 15 mg / 16 hours patch (Step 2). This should be continued for the remainder of the 8 week course, before stepping down to the 10 mg / 16 hours patch (Step 3) for 4 weeks. If symptoms persist the advice of a healthcare professional should be sought.

Adults who use NRT beyond 9 months are recommended to seek additional help and advice from a healthcare professional.

Adolescents (12 to 18 years)

The dose and method of use are as for adults however as data are limited in this age group, the recommended treatment duration is 12 weeks. If longer treatment is required, advice from a healthcare professional should be sought.

How to apply the patches

Nicorette Patch should be applied to clean, dry intact areas of hairless skin, for example on the hip, upper arm, or chest. These areas should be varied each day and the same site should not be used on consecutive days.

1. Wash your hands before applying the patch.

2. Cut open the pouch with scissors along the side, as indicated. Select a clean, dry, hairless intact area of skin, such as the hip, upper arm or chest.

3. Peel one part of the silvery aluminium backing away. Avoid touching the sticky surface of the patch with your fingers.

4. Apply the sticky part of the patch carefully onto the skin and peel off the remaining half of the silvery aluminum backing.

5. Press the patch firmly onto the skin with your palm or finger-tips.

6. Rub your fingers firmly round the edge to ensure that the patch sticks firmly.

Use of skin oils or talc can prevent proper adhesion of the patch.

After removal, used patches should be disposed of carefully.

Nicorette Patches should not be administered to patients with known hypersensitivity to nicotine or any component of the patch.

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 Nicorette Patch presents a lesser hazard than continuing to smoke. However dependent smokers currently hospitalised as a result of myocardial infarction, severe dysrhythmia or CVA and who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, Nicorette Patch 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.

Renal or hepatic impairment: Nicorette Patch 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. After removal, the patch should be folded in half, adhesive side innermost, and placed inside the opened sachet, or in a piece of aluminium foil. The used patch should then be disposed of carefully, away from the reach of children or animals.

Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, Nicorette Patch 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.

Generalised dermatological disorders: Patients with chronic generalised dermatological disorders such as psoriasis, chronic dermatitis or urticaria should not use Nicorette Patch.

Angioedema and urticaria have been reported.

Erythema may occur. If it is severe or persistent, treatment should be discontinued.

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 i.e. increase in blood pressure and heart rate and also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration.

Pregnancy

NRT is not contraindicated in pregnancy. The decision to use NRT should be made on a risk-benefit assessment as early on in the pregnancy as possible with the aim of discontinuing use as soon as possible.

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 to assist a quit attempt.

Nicotine passes to the fetus affecting breathing movements and has a dose-dependent effect on placental/fetal circulation. However 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.

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 women is suffering from nausea during pregnancy. If patches are used they should be removed before going to bed.

Lactation

NRT is not contraindicated in lactation. Nicotine from smoking and NRT is found in breast milk. However the amount of nicotine the infant is exposed to 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.

Not applicable.

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.

Nicorette Patch 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 Nicorette Patch has not been found to cause any serious adverse effects. Excessive use of Nicorette Patch by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.

About 20% of Nicorette patch users experience mild local skin reactions, during the first weeks of treatment.

Reported adverse events associated with Nicorette 10mg, 15mg and 25mg Invisi Patch include:

*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), including isolated reports.

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 intake 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.

Nicotine has no therapeutic uses except as replacement therapy for the relief of abstinence symptoms in nicotine-dependent smokers.

Owing to its many actions, the overall effects of nicotine are complex. A wide variety of stimulant and depressant effects are observed that involve the central and peripheral nervous, cardiovascular, endocrine, gastro-intestinal and skeletal motor systems. Nicotine acts on specific binding sites or receptors throughout the nervous system.

The patches are labelled by the average amount of nicotine released over 16 hours.

A linear relationship exists between released amount of nicotine (dose) and plasma levels of nicotine over the therapeutic dose range, 10-25 mg/16 hours The mean peak plasma levels of nicotine (C_max ) achieved are calculated to:

The calculated peak plasma levels are in the same range as true measured peak plasma concentrations: 11 ng/mL for the 10 mg patch and 25 ng/mL for the 25 mg patch. Interpolation yelds a peak plasma concentration of 16 ng/mL for the 15 mg patch.

The maximum level of plasma concentration after administration is reached after approximately 9 hours (t_max). The plasma peak is in the afternoon/ evening when the risk of relapse is highest.

The volume of distribution of nicotine is about 2 to 3 L/kg and the half-life approximately 3 hours. The major eliminating organ is the liver, and average plasma clearance is about 70 L/hour. The kidney and lung also metabolise nicotine. More than 20 metabolites of nicotine have been identified, all of which are believed to be less active than the parent compound.

Plasma protein binding of nicotine is less than 5%. Therefore, changes in nicotine binding from use of concomitant drugs or alterations of plasma proteins by disease states would not be expected to have significant effects on nicotine kinetics.

The primary metabolite of nicotine in plasma, cotinine, has a half-life of 15 to 20 hours and concentrations that exceed nicotine by 10-fold.

The primary urinary metabolites are cotinine (12% of the dose) and trans-3-hydroxy-cotinine (37% of the dose). About 10% of nicotine is excreted unchanged in the urine.

Progressive severity of renal impairment is associated with decreased total clearance of nicotine. Raised nicotine levels have been seen in smoking patients undergoing hemodialysis.

The pharmacokinetics of nicotine is unaffected in cirrhotic patients with mild liver impairment (Child score 5) and nicotine clearance is decreased in cirrhotic patients with moderate liver impairment (Child score 7).

A minor reduction in total clearance of nicotine has been demonstrated in healthy elderly patients, however, not justifying adjustment of dosage.

Plasma nicotine concentrations show dose proportionality for the three patch doses.

Preclinical data indicate that nicotine is neither mutagenic nor genotoxic.

There are no other findings derived from preclinical testing of relevance to the prescriber in determining the safety of the product which have not been considered in other relevant sections of this Summary of Product Characteristics.

Triglycerides, medium-chain

basic butylated methacrylate copolymer

Polyethylenterephthalate film (PET)

Acrylate Matrix

Acrylic adhesive solution

Potassium hydroxide

Croscarmellose sodium

Aluminium acetylacetonate

Release Liner

Polyethylenterephthalate (PET) film single side aluminised, both sides siliconised

Blending varnish

Printing ink beige

Printing ink brown

Not applicable.

36 months.

Do not store above 25° C.

Package sizes: 15 mg/16 h 7 and 14 patches

All pack sizes may not be marketed.

Each patch is packed in a heat-sealed laminate pouch consisting of paper, PET film, aluminium acrylnitrilcopolymer.

Nicotine residues in the used patches may present a hazard to children and pets, thus used patches should be folded, sticky sides together, put back in an empty pouch and placed in household rubbish.

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom

PL 15513/0160

02 December 2008

02 December 2008