Nicorol Toffee 2 Mg Pastilles
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nicorol Toffee 2 mg pastilles
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each pastille contains 2 mg nicotine.
This medicinal product contains 11.5 mg sodium and 334.9 mg sorbitol per pastille.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Pastille
Round, light brown/brown pastille embossed N2 on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Nicorol Toffee pastilles are to be used for the treatment of tobacco dependence by relief of nicotine withdrawal symptoms, including cravings, during a quit attempt (see section 5.1). Permanent cessation of tobacco use is the eventual objective.
Nicorol Toffee pastilles should preferably be used in conjunction with a behavioural support program.
4.2 Posology and method of administration
Adults and elderly
Smokers are advised to stop smoking completely during treatment with Nicorol Toffee pastilles. The initial dose of Nicorol Toffee will be dependent on the patients’ nicotine dependence.
Nicorol Toffee pastilles are not directly interchangeable with other NRT products containing nicotine.
The following table provides an approximate guidance for selecting optimal dosage:
Number of cigarettes / day Suggested Dosage
around 20 - 30 2 mg
about more than 30 cigarettes 4 mg
The 4 mg dose is also recommended after previous failure with Nicorol Toffee 2 mg pastilles.
If 2 mg pastilles prove to be too strong, patients are recommended to take advice from the pharmacist for reducing the dosage further.
One pastille should be taken every 1-2 hours. The usual dosage is 8 - 12 pastilles per day. The maximum daily dose is 60mg (30 pastilles for the 2 mg strength).
The duration of the treatment is individual, but is normally 2-3 months; the dose of nicotine is then gradually reduced. Treatment should be discontinued when the dose has been reduced to 1 - 2 pastilles per day. If further dose reduction is required, the patients should consult the pharmacist.
Use beyond 6 months is generally not recommended however, some exsmokers may need treatment longer to avoid returning to smoking. In this case treatment should be supervised by a healthcare professional.
Professional counselling may help smokers to quit.
Directions for use:
The pastille should be moistened in the mouth and then moved to either cheek cavity. At intervals, the pastille should be moved from one side of the mouth to the other, the action should be repeated until the pastille is completely dissolved (20 - 30 minutes). The pastille should not be aggressively sucked, chewed or swallowed whole.
Simultaneous use of food and drinks should be avoided while using the pastille. Drinks that lower pH in the oral cavity, e.g. coffee, fruit juice and soft drinks, may decrease the absorption of nicotine. To obtain maximal absorption of nicotine these kinds of drinks should be avoided up to 15 minutes before the pastilles are used.
Children and adolescents (< 18 years)
Nicorol Toffee pastilles should not be administered to persons under the age of 18 without recommendation from a physician. There is no experience in treating adolescents under the age of 18 with Nicorol Toffee pastilles.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients. Non-smokers
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: Dependent smokers who are hospitalised with MI, severe dysrhythmia or CVA, who are considered to be haemodynamically unstable, and dependent smokers with unstable or worsening angina (including Prinzmetal’s angina) or uncontrolled hypertension, should be encouraged to stop smoking with nonpharmacological interventions. If this fails, Nicorol Toffee pastilles may be considered, but as data on safety in this patient group are limited, initiation should only be under close medical supervision. In stable cardiovascular disease Nicorol Toffee pastilles presents a lesser hazard than continuing to smoke. However, Nicorol Toffee pastilles should be used with caution in patients with hypertension, stable angina pectoris, cerebrovascular disease, occlusive peripheral arterial disease or cardiac insufficiency.
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 and or hepatic impairment: 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 (see also section 4.9 Overdose). Products containing nicotine should not be left where they may be misused, handled or ingested by children.
Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, Nicorol Toffee pastilles 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.
Swallowed nicotine may exacerbate symptoms in patients suffering from active oesophagitis, oral and pharyngeal inflammation, gastritis or peptic ulcer.
Nicorol Toffee pastilles contain sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Nicorol Toffee pastilles contain 0.5 mmol (11.5mg) sodium per pastille. To be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interaction
No information is available on interactions between Nicorol Toffee pastilles and other medicinal products.
Smoking is associated with increase in CYP1A2 activity. After cessation of smoking, reduced clearance of substrates for this enzyme may occur. This may lead to an increase in plasma levels for some medicinal products of potential clinical importance. The following may require a decrease in dose at cessation of smoking: Caffeine, theophylline, imipramine, pentazocine, phenacetin, phenylbutazone, tacrine, clompiramine, olanzapine, fluvoxamine, flecainide, clozapine, ropirinol and beta-adrenergic blockers e.g. prazosin and propranolol.
Increased subcutaneous adsorption of insulin which occurs upon smoking cessation may necessitate a reduction in insulin dose.
A decrease in circulating catecholamines upon smoking cessation may require an increase in dose of adrenergic agonists e.g. isoprenaline and salbutamol.
Other reported effects of smoking include a reduction of the analgesic effects of propoxyphene, reduced diuretic response to furosemide and altered responder rates in ulcer healing with H2 - antagonists. Adjustment in the doses of these drugs may also be required.
4.6 Pregnancy and lactation
Pregnancy
Smoking during pregnancy, especially during the third trimester 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.
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 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 the pastilles by the pregnant highly dependent smoker should only be initiated after advice from a physician. In the third trimester nicotine has haemodynamic effects (e.g. changes in foetal heart rate) which could affect the foetus close to delivery. Therefore, after the sixth month of pregnancy, the pastilles should only be used under medical supervision in pregnant smokers who have failed to stop smoking by the third trimester.
Lactation
Nicotine is excreted in breast milk in quantities that may affect the child even with therapeutic doses. Nicorol Toffee pastilles, like smoking itself, should therefore be avoided during breast-feeding. Should smoking cessation not be achieved, use of the pastilles by breast feeding smokers should only be initiated after advice from a physician. Where nicotine replacement therapy is used whilst breast-feeding, the pastilles should be taken just after breastfeeding and not during the two hours before breast-feeding.
4.7 Effects on ability to drive and use machines
There is no evidence of any risks associated with driving or operating machinery when Nicorol Toffee pastilles are used following the recommended dose. Nevertheless, smoking cessation can cause behavioural changes.
4.8 Undesirable effects
Nicorol Toffee pastilles can cause adverse reactions similar to those associated with nicotine administered by smoking. These can be attributed to the pharmacological effects of nicotine, which are dose-dependent.
Most of the side effects reported by patients generally occur during the first 34 weeks after initiation of therapy. Nicorol Toffee pastilles may sometimes cause a slight irritation of the throat and increase salivation at the start of treatment. This can be attributed to the pharmacological effects of nicotine, which are dose dependent.
Excessive swallowing of nicotine released in the saliva may, at first, cause hiccups. Patients with a tendency to indigestion may suffer initially from slight dyspepsia or heartburn. Using the pastille as described in section 4.2. e.g. allowing the pastille to dissolve in the cheek cavity, will usually overcome this problem.
Excessive consumption of pastilles by subjects who have not been in the habit of inhaling tobacco smoke, could possibly lead to nausea, faintness and headache.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Very common (>1/10)
General disorders and administration site conditions: bitter taste
Common (>1/100 to <1/10)
Nervous system disorders: headache, dizziness.
Respiratory, thoracic and mediastinal disorders: pharyngitis Gastrointestinal disorders: nausea, flatulence, hiccups, epigastritis General disorders and administration site conditions: dryness of the mouth, irritation of the oral cavity and oesophagus, nasal congestion, cough.
Uncommon (>1/1,000 to <1/100)
Cardiac disorders: palpitations
Rare (>1/10,000 to <1/1,000)
Cardiac disorders: atrial arrhythmia
Immune system disorders: hypersensitivity, angioneurotic oedema and anaphylactic reactions.
Certain symptoms such as dizziness, headache and insomnia may be ascribed to withdrawal symptoms in connection with smoking cessation and may be due to insufficient administration of nicotine. Aphthous ulcer may develop in connection with smoking cessation, but any relation with nicotine treatment is unclear. The patient may still experience nicotine dependence after smoking cessation.
4.9 Overdose
In overdose, symptoms corresponding to heavy smoking may be seen.
The acute lethal oral dose of nicotine is about 0.5-0.75 mg per kg body weight, corresponding in an adult to 40-60 mg. Even small quantities of nicotine are dangerous in children, and may result in severe symptoms of poisoning which may prove fatal. If poisoning is suspected in a child, a doctor must be consulted immediately.
In adults overdose with Nicorol Toffee pastilles may only occur if too many pastilles are sucked simultaneously. Nicotine toxicity after ingestion will most likely be minimised as a result of early nausea and vomiting that occur following excessive nicotine exposure.
General symptoms of nicotine poisoning include: weakness, perspiration, salivation, throat burn, nausea, vomiting, diarrhoea, abdominal pain, hearing and visual disturbances, headache, tachycardia and cardiac arrhythmia, hypotension, dyspnoea, prostration, circulatory collapse, coma and terminal convulsions.
Treatment of overdosage:
All nicotine intake should cease immediately and the patient should be treated symptomatically.
Artificial respiration with oxygen should be instituted if necessary. Administration of oral activated charcoal and gastric lavage should be considered as soon as possible and within 1 hour of ingestion. Monitor vital signs and treat symptomatically.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drug used in nicotine dependence ATC code: N07BA01
Nicotine is an agonist at nicotine receptors in the peripheral and central nervous system and has pronounced CNS and cardiovascular effects. When consumed in tobacco products, it has been shown to be addictive and abstinence is linked to craving and withdrawal symptoms. These craving and withdrawal symptoms include urge to smoke, depressed mood, insomnia, irritability, frustration or anger, anxiety, difficulty in concentrating, restlessness and increased appetite or weight gain. Cravings and other symptoms of nicotine withdrawal are at their most intense during the first few weeks of a quit attempt, diminishing thereafter. The pastilles replace some of the nicotine provided by tobacco and clinical studies measuring intensity of cravings and other withdrawal symptoms have been shown to alleviate these symptoms when they are at their most intense.
5.2 Pharmacokinetic properties
The absorbed amount of nicotine depends on the amount released into the mouth and absorbed through the buccal mucosa.
A proportion, by the swallowing of nicotine containing saliva, reaches the stomach and intestine where it is inactivated. Simultaneous intake of drinks that lower pH in the oral cavity may strongly reduce the absorption of nicotine. Due to the first-pass effect in the liver, the systemic bioavailability of nicotine is low. Consequently, in the treatment with Nicorol Toffee pastilles the high and quick systemic nicotine concentration as seen when smoking, is rarely obtained.
Distribution volume after i.v. administration of nicotine is approximately 2-3 l/kg and the half-life is 2 hours. Nicotine is metabolised primarily in the liver and the plasma clearance is approximately 1.2 l/min, but nicotine is also metabolised in the kidney and lungs. Nicotine crosses the blood-brain barrier.
More than 20 metabolites have been identified all believed to be less active than nicotine. The main metabolite is cotinine which has a half-life of 15-20 hours and with approximately 10 times higher plasma concentration than nicotine. Nicotine’s plasma protein binding is less than 5%. Changes in nicotine binding from the use of concomitant drugs or due to altered disease state are not expected to have significant effect on nicotine kinetics. The main metabolite in urine is cotinine (15% of the dose) and trans-3-hydroxy cotinine (45% of the dose).
About 10% of the nicotine is excreted unchanged. Up to 30% may be excreted with urine in increased diuresis and the acidity under pH 5.
The peak value for the plasma concentration of 2 mg pastille at steady state is approximately 11 nanogram per ml (average plasma concentration of nicotine after smoking one cigarette is 15-30 nanogram per ml). Peak plasma concentration is about 30 minutes at steady state.
5.3 Preclinical safety data
Nicotine was positive in some in-vitro genotoxicity tests but there are also negative results with the same test systems. Nicotine was negative in in-vivo tests.
Animal experiments have shown that nicotine induces post-implantation loss and reduces the growth of foetuses.
The results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine.
PHARMACEUTICAL PARTICULARS
6
6.1 List of excipients
Acacia, spray-dried
Sorbitol, liquid (Non-crystallising) (E420)
Xylitol
Sodium dihydrogen phosphate dihydrate Tri-sodium phosphate dodecahydrate Sodium hydroxide Talc
Maize starch
Capol (contains white beeswax and vegetable oil) Toffee flavour QL17192 which contains:
- Natural flavouring substance
- Propylene glycol
- Ethyl alcohol 95%
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 years
6.4 Special precautions for storage
Do not store above 30oC.
Store in the original package in order to protect from moisture.
6.5 Nature and contents of container
PVC/PVdC Aluminium blisters containing 2, 14, 20, 28, 42, 56, 60, 72, 100 pastilles.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Actavis Group PTC ehf., Reykjavikurvegur 76-78, IS - 220 Hafnarfjordur, Iceland
8 MARKETING AUTHORISATION NUMBER(S)
PL 30306/0286
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
04/03/2009
10
DATE OF REVISION OF THE TEXT
04/03/2009