Nicorette Invisi Transdermal Patch

Nicotine.

Active Ingredient: Nicotine 1.75 mg/cm².
Transparent patch for topical application available in sizes of 22.5cm²/13.5cm²/9.0cm².
Nicorette lnvisi Transdermal Patch 10mg/15mg/25mg per 16 Hours is a semi-transparent, beige, imprinted, 9.0cm²/13.5cm²/22.5cm², rectangular Transdermal Therapeutic System (TTS), with rounded corners. It consists of pre-coated backing layer, nicotine source layer, and a skin contact adhesive layer on a pre-coated aluminized and siliconized release liner, and contains 15. 75mg/23.62mg/39.37mg nicotine.
Excipients/Inactive Ingredients: Medium chain triglycerides, basic butylated methacrylate copolymer, polyethylenterephthalate film (PET), acrylic adhesive solution, potassium hydroxide, croscarmellose sodium, aluminium acetylacetonate and siliconized PET release liner with aluminized single side.

Pharmacotherapeutic Group: Drug used in nicotine dependence. ATC Code: N07BA01.
Pharmacology: Pharmacodynamics: Abrupt cessation of the established, regular use of tobacco-containing products results in the characteristic syndrome, with withdrawal symptoms including cravings (urges to smoke) as described as follows.
Regardless of the means used, a variety of symptoms are known to be associated with quitting habitual tobacco use. These include emotional or cognitive effects such as dysphoria or depressed mood; insomnia; irritability, frustration or anger; anxiety; difficulty concentrating, and restlessness or impatience. There may also be physical effects such as decreased heart rate; increased appetite or weight gain, dizziness or presyncopal symptoms, cough, constipation, gingival bleeding or apthous ulceration, or nasopharyngitis. In addition, and of clinical significance, nicotine cravings may result in profound urges to smoke.
Clinical studies have shown that nicotine replacement products can help smokers abstain from or reduce their smoking by relieving these withdrawal symptoms.
Patch treatment mimics the fluctuations of nicotine over the day in smokers, with no nicotine administration during sleep. Daytime nicotine patch treatment does not give the nicotine induced sleep disturbances seen with nicotine administration during sleep.
Pharmacokinetics: All patches are labelled by the average amount of nicotine absorbed by the average patient over 16 hours.
Representative mean values of C_max for the patches are presented in the table as follows: (See Table 1.)

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The calculated peak plasma levels are in the same range as true measured peak plasma concentrations: 11 ng/ml for the 10mg patch and 24.2ng/ml for the25mg patch. Interpolation yields a peak plasma concentration of 15.4ng/ml for the 1 5mg 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 is approximately 3 hours. The major eliminating organ is the liver, although the lungs and brain also metabolise nicotine to a small extent. The enzyme primarily involved in biotransformation of nicotine is CYP2 A6. Seventeen 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 considered to be low, about 5%. Therefore, changes in nicotine binding from the 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 terminal half-life of 14 to 20 hours; the plasma concentrations of cotinine exceed those of nicotine by 10-fold.
The primary urinary metabolites are cotinine (10-12% of the dose) and trans-3-hydroxy-cotinine (28-37% of the dose). About 10-15% 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 haemodialysis.
The pharmacokinetics of nicotine is unaffected in cirrhotic patients with mild liver impairment (Child-Pugh score 5) and nicotine clearance is decreased by about40-500/o in cirrhotic patients with moderate liver impairment (Child-Pugh 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.

For treatment of tobacco dependence by relieving nicotine craving and withdrawal symptoms thereby facilitating smoking cessation in smokers motivated to quit.
Advice and support normally improve the success rate.

The patient should make every effort to stop smoking completely during treatment with Nicorette lnvisi Transdermal Patch. Advice and support normally improve the success rate.
Adults and the Elderly: The patch should be applied to an intact area of the skin upon waking up in the morning and removed at bedtime.
Heavy smokers (those smoking 15 or more cigarettes in a 24-hour period) are recommended to start at Step 1 with the 25mg/1 6 hours patch and use one patch daily for 8 weeks.
Gradual weaning from the patch should then be initiated. One 15mg/16 hours patch should be used daily for 2 weeks followed by one 1 0mg/16 hours patch daily for 2 weeks.
Light smokers (those smoking less than 15 cigarettes in a 24-hour period) are recommended to start at Step 2 (15mg/16 hours patch) for 8 weeks and decrease the dose to Step 3 (1 0mg/16 hours patch) for the final 4 weeks. (See Table 2.)

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Combination therapy: Highly dependent smokers, smokers who experience "breakthrough" cravings or those who have failed with single N RT treatment, can use a flexible smoking cessation format, in combination with the patch for fast relief of cravings.
Children and Adolescents Nicorette lnvisi Transdermal Patch should not be administered to persons under 1 8 years of age without recommendation from a healthcare professional.
There is limited experience of treating this age group with Nicorette lnvisi Transdermal Patch.
Use of the patch beyond 6 months is generally not recommended. Some ex-smokers may need longer treatment to avoid returning to smoking.
How to apply the patches: Nicorette lnvisi Transdermal 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 as far as possible. Avoid touching the sticky surface of the patch with your fingers, as much as possible.
4. Apply the sticky part of the patch carefully onto the skin and peel off the remaining half of the silvery aluminium 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.
7. If the patch comes off, replace with a new one. Use of skin oils or talc can prevent proper adhesion of the patch.
After removal, used patches should be disposed of carefully.
The patches should be folded after use with the sticky side inwards, put back in an empty pouch and disposed of where children cannot reach it.
Administration of nicotine should be stopped temporarily if any symptoms of nicotine excess occur. Nicotine intake should be decreased by either lowering dosing frequency or strength if nicotine excess symptoms persist. Please refer to symptoms and treatment of overdose for further details.
Route of administration: Apply on dry intact area of skin.

Symptoms and Treatment of Overdose: Excessive use of nicotine from either nicotine replacement products and/or smoking might cause symptoms of an overdose.
Overdosage with nicotine can occur if many patches are used simultaneously or if the user has very low nicotine dependence or uses other forms of nicotine concomitantly, including smoking.
Symptoms of overdose are those of acute nicotine poisoning and include nausea, vomiting, increased salivation, abdominal pain, diarrhea, sweating, headache, dizziness, disturbed hearing and marked weakness. At high doses, these symptoms may be followed by hypotension, weak and irregular pulse, breathing difficulties, prostration, circulatory collapse and general convulsions.
Doses of nicotine that are tolerated by adult smokers during treatment may produce severe symptoms of poisoning in small children and may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.
Management of overdose: Administration of nicotine must be stopped immediately and the patient must be treated symptomatically. Remove patch and rinse application site with water. If excessive amount of nicotine is swallowed, activated charcoal reduces the gastrointestinal absorption of nicotine.

Hypersensitivity to nicotine or any of the components of the patch.

A risk benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions: Dependent smokers with a recent myocardial infarction, unstable or worsening angina including Prinzmetal's angina, severe cardiac arrhythmias, recent cerebrovascular accident, and or who suffer with uncontrolled hypertension should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, the Nicorette patch may be considered but as data on safety in this patient group are limited, initiation should only be under close medical supervision.
Patients with diabetes mellitus should be advised to monitor their blood sugar levels more closely than usual when smoking is stopped and NRT is initiated, as reductions in nicotine-induced catecholamine release can affect carbohydrate metabolism.
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.
Nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastric or peptic ulcers and NRT preparations should be used in caution in these conditions.
Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.
Doses of nicotine tolerated by smokers can produce severe toxicity in children that may be fatal. Products containing nicotine should not be left where they maybe handled or ingested by children, see Overdose.
Nicorette Invisi Transdermal Patch should be removed prior to undergoing any Magnetic Resonance Imaging (MRI) procedures to prevent the risk of burns.

Nicotine passes to the foetus and affects its breathing movements and circulation. The effect on the circulation is dose-dependent. Therefore the pregnant smoker should always be advised to stop smoking completely without the use of nicotine replacement therapy. The risk of continued smoking may pose greater hazard to the foetus as compared with the use of nicotine replacement products in a supervised smoking cessation programme. Use of Nicorette lnvisi Transdermal Patch by the pregnant smoker should only be initiated after advice from a healthcare professional.
Nicotine passes freely into breast milk in quantities that may affect the child, even with therapeutic doses. The use of Nicorette lnvisi Transdermal Patch should therefore be avoided when breastfeeding. Should smoking cessation not be achieved, use of the Nicorette lnvisi Transdermal Patch by breastfeeding smokers should only be initiated after advice from a healthcare professional.

Most of the undesirable effects reported by the subjects occur during the early phase of treatment and are mainly dose-dependent. Allergic reactions (including symptoms of anaphylaxis) occur rarely during use of Nicorette Invisi Transdermal Patch.
About 20% of users experienced mild local skin reactions during the first weeks of treatment. As would be expected, the types of adverse reactions seen for the Nicorette lnvisi Transdermal Patch in clinical trials are similar to those associated with nicotine administered by other means.
Clinical Trial Data: The safety of nicotine from clinical trial data is based on data on a meta-analysis of randomized clinical trials (RCTs) for the treatment of smoking cessation.
ADRs with patch formulations identified from clinical trials are presented below in Table 3.
Table 3: ADRs Reported with a frequency ≥1 % identified from Meta-analysis of Clinical Trial Data with Nicotine Patch formulations. (See Table 3.)

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Post Marketing Data Preferred Term: Post Marketing Data: Adverse drug reactions first identified during post-marketing experience with nicotine are presented in Table 4. Frequencies are provided according to the following convention: Very common; Common; Uncommon; Rare; Very rare; Not known. (See Table 4.)

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Smoking (but not nicotine) is associated with increased activity of CYP1 A2.After giving up smoking, clearance of certain medications which are metabolized via CYP1 A2 may be reduced. This may lead to increased plasma levels of certain medications. The increase may be of clinical significance for products with narrow therapeutic windows, e.g. theophylline, tacrine, clozapine or ropinirole.
Plasma level of other medications which are in part metabolized via CYP1 A2,e.g. imipramine, olanzapine, clomipramine and fluvoxamine, might also rise after stop smoking. There are no data supporting this, however, and the possible clinical significance of this effect on these medications is unknown.
Limited data indicates that the metabolism of flecainide and pentazocine might also be capable of being induced by smoking.

Dispose used patches sensibly.
Do not use if the patient is pregnant or breastfeeding.
Not for sale to or use by persons under age 18.

Do not store above 30°C.

Drugs Used in Substance Dependence

N07BA01 - nicotine ; Belongs to the class of drugs used in the management of nicotine dependence.

NP