1. Name Of The Medicinal Product
Nicorette combi patch + gum.
2. Qualitative And Quantitative Composition
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.
Icy white 2 mg gum: Chewing gum containing 2mg nicotine, as nicotine resinate.
For a full list if excipients, see section 6.1.
3. Pharmaceutical Form
Transdermal patch.
Semi-transparent, beige, imprinted 13.5 cm2 rectangular TTS with rounded corners. Centrally located on a rectangular, aluminised and siliconised release liner.
Medicated chewing gum.
A square, coated, white coloured piece of gum.
4. Clinical Particulars
4.1 Therapeutic Indications
Nicorette combi patch + gum is indicated for the relief of nicotine withdrawal symptoms as an aid to smoking cessation in adults and children over 12 years of age.
It is used for smokers who smoke 10 or more cigarettes per day, individuals who experience acute or breakthrough cravings, or those who have failed with single treatment. The patch provides background nicotine levels while the gum is used for immediate relief of cravings. Combination treatment has been shown to have greater success rates than either patch or gum alone.
If possible, nicorette combi patch + gum should be used in conjunction with a behavioural support programme.
4.2 Posology And Method Of Administration
Nicorette combi patch + gum is a smoking cessation preparation consisting of a 15mg/16 hour invisi patch and an icy white 2mg chewing gum. The patient should initially use the invisi patch and icy white gum together to control cravings. After 12 weeks of treatment, the invisi patch should be discontinued and the patient should be weaned off nicotine using the icy white gum only – see table below.
The patient should make every effort to stop smoking completely during treatment with this product.
Behavioural therapy, advice and support will normally improve the success rate.
Adults (over 18 years of age)
Initial treatment | ||
| Invisi patch | Icy white 2mg gum |
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How to apply the Patch
The invisi 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. There is no clinically significant difference in bioavailability of nicotine when the patch is applied to either the hip, upper arm or chest.
1. Wash your hands before applying the invisi 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 invisi patch carefully onto the skin and peel off the remaining half of the silvery aluminum backing.
5. Press the invisi patch firmly onto the skin with your palm or finger- tips.
6. Rub your fingers firmly round the edge to ensure that the invisi patch sticks firmly.
Use of skin oils or talc can prevent proper adhesion of the invisi patch.
After removal, used invisi patches should be disposed of carefully.
It is intended that the invisi patch be worn through the waking hours (approximately 16 hours) being applied on waking and removed at bedtime. After 12 weeks the invisi patch should be discontinued.
Gum
The icy white gum should be chewed according to the instructions.
The icy white gum should be used whenever there is an urge to smoke according to the 'chew and rest' technique described on the pack. After about 30 minutes of such use, the gum will be exhausted. Use a minimum of four 2mg icy white gums per day; usually 5 – 6 icy white gums will be adequate for effect. Not more than 15 pieces of the icy white chewing gum may be used each day. Absorption of nicotine is through the buccal mucosa, any nicotine that is swallowed being destroyed by the liver.
Any icy white gums which remain following the initial 12 week period should be retained and used during the weaning period.
Weaning
For patients who have successfully abstained from smoking for 12 weeks using nicorette combi patch + gum, the invisi patches should be discontinued and the patient should be supported through a further 6-12 week weaning period using the same dosage of icy white gum as in the initial treatment phase. The amount of icy white gum used is then gradually reduced up to 9 months from the start of treatment. When daily use is 1-2 icy white gums, use should be stopped.
Any spare icy white gum should be retained as a craving may suddenly return.
Adults who use NRT beyond 9 months for smoking cessation are recommended to seek additional help and advice from a healthcare professional.
Adolescents (12 to 18 years)
The patient should make every effort to stop smoking completely during treatment with nicorette combi patch + gum.
The dose and method of use are as for adults. However, as data are limited in this age group, the recommended duration of treatment is 12 weeks. If longer treatment is required, advice from a healthcare professional should be sought.
The 12 week period should be made up as follows. For the first eight weeks, both the invisi patch and icy white gum should be used. The use of invisi patch should be discontinued after this period. For the remaining 4 weeks, only the icy white gum should be used and the amount should be gradually reduced until daily use is only 1-2 icy white gums. At this point, gum use should be discontinued completely.
4.3 Contraindications
Hypersensitivity to nicotine or any other components of the invisi patch or icy white gum.
4.4 Special Warnings And Precautions For Use
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 combi patch + gum 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 combi patch + gum 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 combi patch + gum 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 invisi patch should be folded in half, adhesive side innermost, and placed inside the opened sachet, or in a piece of aluminium foil. The used invisi patch should then be disposed of carefully, away from the reach of children or animals. The icy white gum should also be disposed of with care.
Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, nicorette combi patch + gum 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.
Invisi patch only
Generalised dermatological disorders: Patients with chronic generalised dermatological disorders such as psoriasis, chronic dermatitis or urticaria should not use the patch.
Angioedema and urticaria have been reported.
Erythema may occur. If it is severe or persistent, treatment should be discontinued.
Minor skin reactions are seen at the patch application site in a proportion of patients when commencing treatment (see also section 4.8). If skin reactions become more severe or more generalized, patients should be advised to discontinue use of patches and seek further medical help regarding nicotine replacement therapy
Icy white gum only
GI disease: Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastritis or peptic ulcers and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.
Denture warning: Smokers who wear dentures may experience difficulty in chewing the icy white gum. The chewing gum may stick to, and may in rare cases damage dentures.
Excipients: The icy white gum also contains butylated hydroxytoluene (E321); this may cause irritation to the mucous membranes.
Special warnings and precautions for the combination of nicotine gum with nicotine patch are the same as those for each treatment alone.
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 i.e. increase in blood pressure and heart rate and also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration.
4.6 Pregnancy And Lactation
Nicorette combi patch + gum should not be used in pregnancy or lactation. However, NRT monotherapy may be recommended dependent on a risk benefit assessment.
4.7 Effects On Ability To Drive And Use Machines
Not applicable.
4.8 Undesirable Effects
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 combi patch + gum 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 combi patch + gum has not been found to cause any serious adverse effects. Most of the undesirable effects reported by patients occur during the first few weeks after start of treatment. About 20% of patch users experience mild local skin reactions during the first few weeks of treatment. In some patients the skin reactions may become more severe eg skin blistering or a burning sensation or may be more generalized (see section 4.4).
Excessive use of nicorette combi patch + gum by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.
Nicotine from the gum may sometimes cause a slight irritation of the throat at the start of treatment and may also cause increased salivation. Excessive swallowing of dissolved nicotine may, at first, cause hiccupping.
The chewing gum may stick to, and may in rare cases damage dentures.
Reported adverse events associated with invisi 15mg patch include:
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Reported adverse events associated with icy white 2mg gum include:
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*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.
Adverse reactions that may occur when using the combination treatment (invisi patch and icy white gum) only differ from each treatment alone in terms of local adverse events associated with the formulations. The frequencies of these adverse events are comparable to those reported in the SPCs for the respective Nicorette products.
4.9 Overdose
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.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Drugs used in nicotine dependence
ATC code: N07B A01
The pharmacological effects of nicotine are well documented. Owing to its many actions, the overall effects of nicotine are complex. The response at any one time represents a summation of stimulant and depressant actions from direct, reflex and chemical mediator influences on several organs. The main pharmacological actions are central stimulation and/or depression; transient hyperpnoea; peripheral vasoconstriction (usually associated with a rise in systolic pressure); suppression of appetite and stimulation of peristalsis. Nicotine acts on specific binding sites or receptors throughout the nervous system.
The icy white gum contains a number of ingredients that are recognized as having properties for removal of dental staining. Clinical studies have shown that the gum helps to improve tooth whiteness.
5.2 Pharmacokinetic Properties
Pharmacokinetic properties of Nicorette invisi patch
The invisi 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 (Cmax ) achieved are calculated to:
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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 10 mg patch and 25 ng/mL for the 25 mg patch. Interpolation yields 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 (tmax). 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 patch doses.
Pharmacokinetic properties of Nicorette icy white chewing gum.
Nicotine administered in chewing gums is readily absorbed from the buccal mucous membranes. Demonstrable blood levels are obtained within 5 – 7 minutes and reach a maximum about 30 minutes after the start of chewing. Blood levels are roughly proportional to the amount of nicotine chewed and have been shown never to exceed those obtained from smoking cigarettes.
Pharmacokinetic properties of the Combination of Nicorette invisi patch and Nicorette icy white chewing gum.
The plasma levels of nicotine when combining one 15mg patch and 2mg chewing gums will depend on the number of chewed gums and the dosing interval.
The combination of the 15mg/16 hour patch and twenty four 2mg gums, i.e. 1 patch + 24 gums per 16 hours resulted in maximum plasma levels of about 39 ng/mL.
A simulation of plasma concentrations shows that if one 15mg/16 hour patch is applied in the morning and five to six 2mg chewing gums are evenly distributed over the awake hours according to the recommended dosage, a maximum plasma level of about 19 - 20ng/mL will be reached. This simulation is based on nicotine pharmacokinetics upon separate use of the 15mg patch and 2mg gums, respectively.
The actual and simulated data above is based on use of the original nicorette 15mg patch and classic 2mg gum. These formulations are bioequivalent to nicorette invisi 15mg patch and icy white 2mg gum respectively.
5.3 Preclinical Safety Data
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.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Invisi patch:
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
Printing Inks
Blending varnish
Printing ink beige
Printing ink brown
Icy white gum:
Core Gum
Chewing gum base, containing butylated hydroxy toluene (E321)
Xylitol
Peppermint oil
Sodium carbonate, anhydrous
Sodium hydrogen carbonate
Acesulfame Potassium
Levomenthol
Magnesium oxide, light
Talc
Sub coating
Winterfresh
Hypromellose
Sucralose
Polysorbate 80
Hard Coating
Xylitol
Starch, pregelatinised
Titanium dioxide (E171)
Winterfresh
Carnauba wax
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
24 months.
6.4 Special Precautions For Storage
Do not store above 25°C.
6.5 Nature And Contents Of Container
Invisi patches: Each patch is packed in a heat-sealed laminate pouch consisting of paper, PET film, aluminium acrylnitrilcopolymer.
Icy white gums: PVC/PVDC/Al blister packed strips each containing 10 pieces of gum.
Each nicorette combi patch + gum pack contains 7 patches and 70 gums.
6.6 Special Precautions For Disposal And Other Handling
Any unused product or waste material should be disposed of in accordance with local requirements.
Invisi patches:
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.
Icy white gum:
Dispose of the gum sensibly.
See section 4.2.
7. Marketing Authorisation Holder
McNeil Products Ltd
Foundation Park
Roxborough Way
Maidenhead
Berkshire
SL6 3UG
United Kingdom
8. Marketing Authorisation Number(S)
PL 15513/0359
9. Date Of First Authorisation/Renewal Of The Authorisation
4th December 2009
10. Date Of Revision Of The Text
20 April 2010
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