1. Name Of The Medicinal Product
Nicotinell® TTS 20
2. Qualitative And Quantitative Composition
Each Nicotinell TTS 20 patch contains 35mg S(-)-nicotine which provides an average absorption rate of 14 mg nicotine in 24 hours.
3. Pharmaceutical Form
Transdermal patch.
The Nicotinell TTS patch is a transdermal therapeutic system, consisting of a round, flat, matrix-type self-adhesive, yellowish-ochre coloured patch. It is protected by a rectangular metallic release liner backing to be discarded before application.
Nicotinell TTS 20 patch 14mg/24 hour has a drug releasing area of 20 cm2 and is printed CG FEF on the patch surface.
4. Clinical Particulars
4.1 Therapeutic Indications
Nicotinell patches relieve and/or prevent cravings and nicotine withdrawal symptoms associated with tobacco dependence. They are indicated to aid smokers wishing to quit or reduce prior to quitting, to assist smokers who are unwilling or unable to smoke, and as a safer alternative to smoking for smokers and those around them.
Nicotinell patches are indicated in pregnant and lactating women making a quit attempt.
Nicotinell patches should preferably be used in conjunction with a behavioural support programme.
4.2 Posology And Method Of Administration
Adults:
For individuals smoking 20 cigarettes or more a day, it is recommended that treatment be started with Nicotinell TTS 30 (Step 1) once daily, applied to a dry non-hairy area of the skin on the trunk or upper arm. Those smoking less than this are recommended to start with Nicotinell TTS 20 (Step 2). Sizes of 30cm2, 20cm2 and 10cm2 are available to permit gradual withdrawal of nicotine replacement, using treatment periods of 3-4 weeks (for each size). The size of patch may be adjusted according to individual response, maintaining or increasing the dose if abstinence is not achieved or if withdrawal symptoms are experienced. Total treatment periods of more than 3 months and daily doses above 30cm2 have not been evaluated. The treatment is designed to be used continuously for 3 months but not beyond. However, if abstinence is not achieved at the end of the 3 month treatment period, further treatments may be recommended.
The dosage must not be adjusted by cutting a patch.
The patch should be used as soon as it has been removed from the child-resistant pouch. Following removal of the metallic backing, the patch should be applied to the skin and held in position for 10-20 seconds with the palm of the hand. Each patch should be removed after 24 hours and disposed of safely (see “Warnings”). A different site of application should be chosen each day and several days should be allowed to elapse before a new patch is applied to the same area of skin.
Use for 24 hours optimizes the effect against morning cravings but in pregnant patients, it is recommended that the patch is removed before going to bed (see section 4.6)
Children and young adults:
The above recommendation can be used for adolescences between 12 and 18 years of age. As data are limited in this age group, medical advice should be obtained should it be found necessary to use the patch beyond 12 weeks.
Elderly:
Experience in the use of these patches in smokers over the age of 65 years is limited. Nicotinell TTS does not appear to pose safety problems in this age group.
Potential for abuse and dependence:
Transdermal nicotine is likely to have a very low abuse potential (see also section 4.4 Transferred Dependence) because of its slow onset of action, low fluctuations in blood concentrations, inability to produce high blood concentrations of nicotine, and the infrequent (once daily) use. Moreover, gradual weaning from the patches is instituted within the treatment schedule, and the risk of dependence after therapy is minimal. The effects of abrupt withdrawal from Nicotinell TTS are likely to be similar to those observed with tobacco withdrawal from comparable nicotine concentrations.
4.3 Contraindications
Nicotinell TTS should not be administered to non-smokers or occasional smokers. The system is contraindicated in diseases of the skin which may complicate patch therapy, and known hypersensitivity to nicotine or any of the components of the patch.
4.4 Special Warnings And Precautions For Use
Any risks that may be associated with nicotine replacement therapy are substantially outweighed by the well established dangers of continued smoking.
Precautions: Users should be informed that if they continue to smoke while using the patches, they may experience increased adverse effects due to the hazards of smoking, including cardiovascular effects.
Underlying cardiovascular disease
In stable cardiovascular disease Nicotinell TTS presents a lesser hazard than continuing to smoke. However dependent smokers currently hospitalized as a result of a recent myocardial infarction, severe dysrhythmia or recent cerebrovascular accident and who are considered to be haemodynamically unstable should be encouraged to stop smoking with non-pharmacological interventions. If this fails, Nicotinell TTS 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 nicotine replacement therapy is initiated as catecholamines released by nicotine can affect carbohydrate metabolism.
Allergic reactions
Discontinuation of treatment may be advisable in cases of severe or persistent allergic reactions.
Angioedema and urticaria have been reported. Contact sensitisation was reported in a few patients using transdermal nicotine in clinical trials. Patients who develop contact sensitisation to nicotine should be cautioned that a severe reaction could occur from smoking or exposure to other nicotine containing products.
Renal and or hepatic impairment
Should be used in caution in patients with moderate to severe hepatic impairment and/or severe impairment as the clearance of nicotine or its metabolites may be decreased with the potential for increased adverse effects.
Gastro-Intestinal disease
Nicotinell TTS should be used with caution in patients with peptic ulcers.
Pheochromocytoma and uncontrolled hyperthyroidism
Nicotinell TTS should be used with caution in patients with uncontrolled hyperthyroidism or pheochromocytoma as nicotine causes release of catecholamines.
Transferred dependence
Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.
Danger in small children
Doses of nicotine that are tolerated by adult and adolescent smokers can produce severe toxicity in small children that may be fatal. Both before and after use, the patch contains a significant amount of nicotine. Subjects must be cautioned that the patches must not be handled casually or left where they might be inadvertently misused or consumed by children. Used patches must be disposed of with care by folding them in half with the adhesive sides inwards, and ensuring that they do not fall into the hands of children under any circumstances.
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 slower metabolism and a consequent rise in blood levels of such drugs.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
No information is available on interactions between Nicotinell TTS and other drugs. 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.
4.6 Pregnancy And Lactation
Pregnancy
Stopping smoking is the single most effective intervention for improving the health of both the pregnant smoker and her baby, and the earlier abstinence is achieved the better. However, if the mother cannot (or is considered unlikely to) quit without pharmacological support, NRT may be used as the risk to the fetus is lower than that expected with smoking tobacco. Stopping completely is by far the best option but Nicotinell patches may be used in pregnancy as a safer alternative to smoking. Because of the potential for nicotine-free periods, intermittent dose forms are preferable, but patches may be necessary if there is significant nausea and/or vomiting. If patches are used they should, if possible, be removed at night when the fetus would not normally be exposed to nicotine.
Lactation
The relatively small amounts of nicotine found in breast milk during NRT use are less hazardous to the infant than second-hand smoke. Intermittent dose forms would minimize the amount of nicotine in breast milk and permit feeding when levels were at their lowest.
4.7 Effects On Ability To Drive And Use Machines
Not applicable.
4.8 Undesirable Effects
In principle, the Nicotinell TTS can cause adverse reactions similar to those associated with nicotine administered by other means (including smoking) and these are mainly dose dependent. Some symptoms such as dizziness, headache, and sleep disturbance may be related to the withdrawal of nicotine associated with stopping smoking. Since the maximum plasma concentrations of nicotine that are produced by the patch are lower than those produced by smoking and fluctuate less, nicotine-related adverse reactions occurring during treatment with the patch can be expected to be less marked than during smoking.
At recommended doses Nicotinell TTS has not been found to cause any serious adverse effects. Excessive consumption of Nicotinell TTS by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.
Some of the symptoms listed below are hard to differentiate from recognised tobacco withdrawal symptoms when comparison with placebo is made. The placebo used contained about 13% of the nicotine of a matching Nicotinell TTS (to match colour and odour for blinding purposes).
The main unwanted effect of Nicotinell TTS is application site reaction. This led to premature discontinuation of patches in about 6% of clinical trial participants. Skin reactions consisted of erythema or pruritus at the patch site. Oedema, burning sensation, blisters, rash, or pinching sensation at the application site was also noted. The majority of these reactions were mild. Most of the skin reactions resolved within 48 hours, but in more severe cases the erythema and infiltration lasted from 1 to 3 weeks. The time of onset of important skin reactions was between 3 and 8 weeks from the start of therapy. In isolated cases the skin reactions extended beyond the application sites. Isolated cases of urticaria, angioneurotic oedema and dyspnoea were reported.
The following are the adverse events/withdrawal symptoms most commonly reported in three double-blind clinical trials irrespective of causal association to study drug.
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Other unwanted experiences reported (irrespective of causal association with Nicotinell TTS) with an incidence of 1% - 5.9% and more frequently than placebo, included: abdominal pain, vomiting, dyspepsia, allergy, motor dysfunction, chest pain, vivid dreams, blood pressure changes, generalised rash, somnolence, impaired concentration and fatigue.
4.9 Overdose
The toxicity of nicotine cannot be directly compared with that of smoking, because tobacco smoke contains additional toxic substances (eg carbon monoxide, and tar).
Chronic smokers can tolerate doses of nicotine that, in a non-smoker, would be more toxic, because of the development of tolerance.
Symptoms
The minimum lethal dose of nicotine in a non-tolerant man has been estimated to be 40 to 60 mg. 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 overdose
If the patient shows signs of overdose, the patch should be removed immediately. The skin surface may be washed with water and dried (no soap should be used). The skin will continue to deliver nicotine into the blood stream for several hours after removal of the system, possibly because of a depot of nicotine in the skin. The patient should then be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
S(-)-nicotine is the most pharmacologically active form of nicotine, the major alkaloid of tobacco. S(-)-nicotine acts primarily on cholinergic receptors of the nicotinic type in the peripheral and central nervous system. For many effects, low doses of S(-)-nicotine have a stimulant action, and high doses a depressant effect. Intermittent administration of S(-)-nicotine affects neurohormonal pathways, and results in the release of acetylcholine, noradrenaline, dopamine, serotonin, vasopressin, beta-endorphin, growth hormone, cortisol and ACTH. These neuroregulators may be involved in the reported behavioral and subjective effects of smoking.
Nicotine replacement therapy is an established therapy as an aid to smoking cessation. Nicotinell TTS provides for a convenient once daily administration by exploiting the fact that S(-)-nicotine is readily absorbed through the skin into the systemic circulation. Placebo-controlled, double-blind studies have shown that nicotine replacement therapy with the patch produces smoking abstinence rates statistically significantly better than placebo, with or without group support. There was also a strong trend towards reduction of withdrawal symptoms.
Application of Nicotinell TTS to smokers abstinent overnight resulted in small increases in mean heart rate and systolic blood pressure and a decrease in stroke volume. The effects were smaller in magnitude than those produced by cigarette smoking.
5.2 Pharmacokinetic Properties
Following a single application of the Nicotinell TTS to the skin of healthy abstinent smokers there is an initial 1-2 hours delay followed by a progressive rise in nicotine plasma concentrations, with a plateau attained at about 8-10 hours after application.
In the majority of subjects the area under the plasma concentration curve (AUC 0-24 hours) varies approximately in proportion to the drug releasing area of the patch. The patch is designed to deliver approximately 0.7mg/cm2/24 hours. In comparison with an i.v. infusion, 76.8% of the nicotine released from the Nicotinell TTS is systemically available. Steady state plasma concentrations after repeated daily administration are within the range observed during moderate cigarette smoking.
Absorption of nicotine over 24 hours varies by a factor of two between different individuals; however within-individual variability is small indicating consistent performance of the transdermal system.
S(-)-nicotine is distributed widely in the body with a volume of distribution of approximately 180 litres. It crosses the blood-brain barrier, placenta and is detectable in breast milk. Plasma protein binding is only 5%. Total plasma clearance of nicotine ranges from 0.92 to 2.43 litres/min. It is eliminated mainly via hepatic metabolism. Only small amounts of nicotine are eliminated in unchanged form via the kidneys, a process which is pH dependent, being negligible under alkaline conditions.
5.3 Preclinical Safety Data
No additional data.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Pad
Polyester film
Acrylate esters vinylacetate co-polymers
Fractionated coconut oil
Methacrylic acid esters co-polymers
Aluminised polyester backing film
Aluminised and siliconised polyester film release liner.
6.2 Incompatibilities
None known.
6.3 Shelf Life
36 months.
6.4 Special Precautions For Storage
Do not store above 25°C
6.5 Nature And Contents Of Container
Heat-seal paper/aluminium/polyamide/polyacrylnitrile pouches (child-resistant) enclosed in a cardboard carton.
or
Heat-sealed paper/ aluminium polyacrylnitrile pouches. Each pouch is enclosed within a child-resistant sachet. Sachets are packed in a cardboard container.
Nicotinell TTS 20 are available in pack sizes of: 2, 3, 7, 14, 21 & 28 patches.
6.6 Special Precautions For Disposal And Other Handling
Keep all medicines out of the reach of children.
7. Marketing Authorisation Holder
Novartis Consumer Health UK Limited
Wimblehurst Road
Horsham
West Sussex
RH12 5AB
Trading as: Novartis Consumer Health.
8. Marketing Authorisation Number(S)
PL 00030/0108
9. Date Of First Authorisation/Renewal Of The Authorisation
Date of first authorisation: 1 August 1997
Date of last renewal: 8 April 2003.
10. Date Of Revision Of The Text
28 July 2011.
LEGAL CATEGORY
GSL
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