Nicabate 2mg Mint Lozenge
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nicabate 2 mg Mint Lozenge
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each lozenge contains 2 mg nicotine (as nicotine resinate).
Excipients with known effect: aspartame (E951) 6 mg, mannitol (E421) 1036 mg, sodium 17 mg and mint flavour (contains lactose and soya protein) 61.2 mg.
For the full list of excipients see Section 6.1.
3 PHARMACEUTICAL FORM
Compressed lozenge
White, round compressed lozenge of 16 mm with convex surfaces, debossed NL2S on one side.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Nicabate Mint Lozenges are indicated for the relief of nicotine withdrawal symptoms including cravings associated with smoking cessation. Nicabate Mint Lozenges should preferably be used in conjunction with a behavioural support programme.
Nicabate Mint Lozenges are indicated in adults and adolescents aged 12 years and over.
4.2 Posology and method of administration
Posology
Adults (18 years and over)
Nicabate Mint Lozenges are suitable for smokers who have their first cigarette of the day more than 30 minutes after waking up.
Behavioural therapy, advice and support will normally improve the success rate.
Abrupt cessation of smoking:
Users should make every effort to stop smoking completely during treatment with Nicabate Mint Lozenges.
Recommended treatment schedule:
|
Step 1 Weeks 1 to 6 |
Step 2 Weeks 7 to 9 |
Step 3 Weeks 10 to 12 |
|
Initial treatment period |
Step down treatment period |
Step down treatment period |
|
1 lozenge every 1 to 2 hours |
1 lozenge every 2 to 4 hours |
1 lozenge every 4 to 8 hours |
During weeks 1 to 6 it is recommended that users take a minimum of 9 lozenges per day. Users should not exceed 15 lozenges per day.
To help stay smoke free beyond 12 weeks, users may take 1-2 lozenges per day only on occasions when they are strongly tempted to smoke.
Those who use the lozenges beyond 9 months are recommended to seek additional help and advice from a healthcare professional.
Paediatric population
Adolescents (12-17 years) should follow the schedule of treatment for abrupt cessation of smoking as given above, but as data are limited, duration of Nicotine Replacement Therapy (NRT) in this age group is restricted to 12 weeks. If longer treatment is required, or where adolescents are unwilling or unable to quit smoking abruptly, advice from a healthcare professional should be sought.
Nicabate Mint Lozenges are contraindicated in children under 12 years of age.
Method of administration
One lozenge should be placed in the mouth and allowed to dissolve. Periodically, the lozenge should be moved from one side of the mouth to the other, and repeated, until the lozenge is completely dissolved (approximately 20 - 30 minutes). The lozenge should not be chewed or swallowed whole.
Users should not eat or drink while a lozenge is in the mouth.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Nicabate Mint Lozenges should not be used by:
• people with hypersensitivity to peanut or soya
• children under the age of 12 years non-smokers.
4.4 Special warnings and precautions for use
The risks associated with the use of NRT are substantially outweighed in virtually all circumstances by the well established dangers of continued smoking.
Dependent smokers with a recent myocardial infarction, unstable or worsening angina including Prinzmetal's angina, severe cardiac arrythmias, uncontrolled hypertension or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological intervention (such as counselling). If this fails, Nicabate Mint Lozenges may be considered, but as data on safety in this patient group are limited, initiation should only be under medical supervision. If there is a clinically significant increase in cardiovascular or other effects attributable to nicotine, the lozenge dose should be reduced or discontinued.
Diabetes : Blood glucose levels may be more variable when stopping smoking, with or without NRT as catecholamines released by nicotine can affect carbohydrate metabolism, so it is important for diabetics to monitor their blood glucose levels more closely than usual while using this product.
Allergic reactions: Susceptibility to angioedema and urticaria
A risk-benefit assessment should be made by an appropriate healthcare professional for patients with the following conditions:
• Renal and hepatic impairment: 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.
• Phaeochromocytoma and uncontrolled hyperthyroidism: Use with caution in patients with uncontrolled hyperthyroidism or phaeochromocytoma as nicotine causes release of catecholamines.
• GIdisease: Swallowing of nicotine may exacerbate symptoms in persons suffering from active oesophagitis, oral or pharyngeal inflammation, gastritis, gastric ulcer or peptic ulcer and oral NRT preparations should be used with caution in these conditions. Ulcerative stomatitis has been reported.
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.
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 a slower metabolism and a consequent rise in blood levels of such drugs.
Transferred dependence: Transferred dependence is rare and is both less harmful and easier to break than smoking dependence.
Phenylketonuria: Nicabate Mint Lozenges contain aspartame which metabolises to phenylalanine, which is of relevance for those with phenylketonuria.
Mannitol: May have a mild laxative effect.
Sodium content: Each Nicabate Mint Lozenge contains 17 mg of sodium. People on a low sodium diet should take this into account.
Lactose content: Consumers with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Nicabate Mint Lozenge.
During a quit attempt users should not interchange Nicabate Mint Lozenges with other nicotine oral dosage forms since pharmacokinetic data indicate a higher availability of nicotine from Nicabate Mint Lozenges in comparison to nicotine gum.
4.5 Interaction with other medicinal products and other forms of interaction
No clinically relevant interactions between nicotine replacement therapy and other drugs have definitely been established, however nicotine may possibly enhance the haemodynamic effects of adenosine.
Smoking cessation itself may require the adjustment of some drug therapy.
4.6 Fertility, Pregnancy and lactation
Pregnancy
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 by a healthcare professional to assist a quit attempt. 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.
However, as nicotine passes to the fetus affecting breathing movements and has a dose dependent effect on placental/fetal circulation, the decision to use NRT should be made as early on in the pregnancy as possible. The aim should be to use NRT for only 2-3 months.
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 woman is suffering from nausea during pregnancy.
Breast-feeding
Nicotine from smoking and NRT is found in breast milk. However the amount of nicotine the infant is exposed to from NRT is relatively small and less hazardous than the second-hand smoke they would otherwise be exposed to.
Ideally smoking cessation during pregnancy should be achieved without NRT. However for women unable to quit on their own, NRT may be recommended by a healthcare professional to assist a quit attempt.
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 made as long as possible. Women should try to breastfeed just before they take the product.
Fertility
There are no relevant data available See section 5.3
4.7 Effects on ability to drive and use machines
Nicabate Mint Lozenges have no or negligible influence on the ability to drive and use machines. However, users of nicotine replacement products should be aware that smoking cessation can cause behavioural changes.
4.8 Undesirable effects
NRT can cause adverse reactions similar to those associated with nicotine administered in other ways including smoking. These may be attributed to the pharmacological effects of nicotine, which are dose dependent. At recommended doses, Nicabate Mint Lozenges have not been found to cause any serious adverse events. Excessive consumption of Nicabate Mint Lozenges by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.
Certain symptoms which have been reported such as depression, irritability, anxiety and insomnia may be related to withdrawal symptoms associated with smoking cessation.
Subjects quitting smoking by any means could expect to suffer from headache, dizziness, increased coughing or a cold.
All related adverse events with a greater incidence in active compared to placebo group in the pivotal efficacy study.
Immune System Disorder Very rare (<1/10000): anaphylactic reactions Blood and lymphatic system disorders Uncommon (□ 1/1000 to <1/100): gingival bleeding
Metabolism and nutrition disorders
Uncommon (□ 1/1000 to <1/100): thirst; excessive thirst
Psychiatric disorders
Common (01/100 to <1/10): insomnia
Uncommon (□ 1/1000 to <1/100): anxiety; anxiety attack; anxiety reaction; nightmares; marked restlessness; decreased appetite; lost appetite; lethargy
Nervous system disorders
Common (□ 1/100 to <1/10): dizziness; headache
Uncommon (□ 1/1000 to <1/100: migraine, mucosal burning; burning sensation; parasthesia mouth; sensory disturbance; hyperalertness; taste perversion
Respiratory, thoracic and mediastinal disorders
Common (01/100 to <1/10): coughing; pharyngitis; sore throat
Uncommon (□ 1/1000 to <1/100): dyspnoea; shortness of breath; aggravated cough; lower respiratory tract infection; respiratory disorder; excessive sneezing
Gastrointestinal disorders
Very common (□ 1/10): nausea; hiccup; flatulence
Common (□ 1/100 to <1/10): vomiting; constipation; diarrhoea; dysphagia; dyspepsia, heartburn, indigestion; belching; mouth irritation, mouth ulceration; tongue ulceration; dry mouth; bloating
Uncommon (□ 1/1000 to <1/100): gastroesophageal reflux; oesophageal reflux aggravated; retching; eructation; gagging; catarrh; increased saliva; lip ulceration; GI disorder; abdominal griping; sore lips; dry throat
Skin and subcutaneous tissue disorders Uncommon (□ 1/1000 to <1/100): itching; rash
General disorders and administration site conditions
Uncommon (□ 1/1000 to <1/100): throat swelling; chest pain; tightness of chest; overdose effect; withdrawal syndrome; malaise; hot flushes; halitosis
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via www.mhra.gov .uk/yellowcard.
4.9 Overdose
The minimum lethal dose of nicotine in a non tolerant man has been estimated to be 40 to 60 mg. Even small quantities of nicotine may be dangerous in children and may prove fatal. Suspected nicotine poisoning in a child should be considered a medical emergency and treated immediately.
Symptoms
Signs and symptoms of an overdose from nicotine lozenges would be expected to be the same as those of acute nicotine poisoning, including pallor, cold sweat, salivation, nausea, vomiting, abdominal pain, diarrhoea, headache, dizziness, disturbed hearing and vision, tremor, mental confusion and weakness. Prostration, hypotension, respiratory failure, rapid or weak or irregular pulse, circulatory collapse and convulsions (including terminal convulsions) may ensue with large overdoses.
Management
In the event of an overdose (e.g. too many lozenges ingested) the user should seek medical attention immediately. All nicotine intake should cease immediately and the patient be treated symptomatically. Artificial respiration with oxygen should be instituted if necessary. Activated charcoal reduces the gastrointestinal absorption of nicotine.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Drugs used in nicotine dependence
ATC Code: N07BA01
Mechanism of action
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. The lozenges replace some of the nicotine provided by tobacco and help reduce the severity of these nicotine craving and withdrawal symptoms.
5.2
Pharmacokinetic properties
Absorption
Nicabate Mint Lozenges completely dissolve in the oral cavity, and the entire amount of nicotine contained in the lozenge becomes available for buccal absorption or ingestion (swallowing). The complete dissolution of Nicabate Mint Lozenge is typically achieved in 20-30 minutes. The peak plasma concentrations of nicotine achieved after a single dose are approximately 4.4 ng/ml. When dosed every 1.5 hours, the steady state peak and trough concentrations are 12.7 and 9.4 ng/ml respectively. Ingestion of Nicabate Mint Lozenges not following dosing instructions (chewed, retained in the mouth, and swallowed; chewed and immediately swallowed) does not result in faster or higher absorption, but a substantial amount of nicotine (80-93%) is still absorbed.
Distribution
As the plasma protein binding of nicotine is low (4.9% - 20%), the volume of distribution of nicotine is large (2.5 l/kg). The distribution of nicotine to tissue is pH dependent, with the highest concentrations of nicotine found in the brain, stomach, kidney and liver.
Biotransformation
Nicotine is extensively metabolized to a number of metabolites, all of which are less active than the parent compound. The metabolism of nicotine primarily occurs in the liver, but also in the lung and kidney. Nicotine is metabolized primarily to cotinine but is also metabolized to nicotine N'-oxide. Cotinine has a half-life of 15-20 hours and its blood levels are 10 times higher than nicotine. Cotinine is further oxidized to trans-3'-hydroxycotinine, which is the most abundant metabolite of nicotine in the urine. Both nicotine and cotinine undergo glucuronidation.
Elimination
The elimination half-life of nicotine is approximately 2 hours (range 1 - 4 hours). Total clearance for nicotine ranges from approximately 62 to 89 l/hr. Non-renal clearance for nicotine is estimated to be about 75% of total clearance. Nicotine and its metabolites are excreted almost exclusively in the urine. The renal excretion of unchanged nicotine is highly dependent on urinary pH, with greater excretion occurring at acidic pH.
5.3 Preclinical safety data
The general toxicity of nicotine is well known and taken into account in the recommended posology. Nicotine was not mutagenic in appropriate assays. The
results of carcinogenicity assays did not provide any clear evidence of a tumorigenic effect of nicotine. In studies in pregnant animals, nicotine showed maternal toxicity, and consequential mild fetal toxicity. Additional effects included pre- and postnatal growth retardation and delays and changes in postnatal CNS development.
Effects were only noted following exposure to nicotine at levels in excess of those which will result from recommended use of Nicabate Mint Lozenges. Effects on fertility have not been established.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Mannitol (E421)
Sodium alginate (E401)
Xanthan gum (E415)
Potassium hydrogen carbonate (E501)
Polycarbophil calcium Anhydrous sodium carbonate (E500i)
Aspartame (E951)
Magnesium stearate (E470b)
Mint flavour powder 57581 (contains lactose and soya protein)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
Shelf life in blister packs: 18 months.
Shelf life in polypropylene tubes: 24 months.
6.4 Special precautions for storage
Do not store above 25°C. Store in the original package.
6.5 Nature and contents of container
Clear or opaque Polyvinyl Chloride/Polyethylene/Polyvinylidene Chloride blisters in packs of 12, 24, 36 and 72, or
Polypropylene tube containing 24 lozenges with reclosable flip top lid, in packs of 24 and 72.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Omega Pharma Ltd.
1st Floor
32 Vauxhall Bridge Road LONDON, SW1V 2SA United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 02855/0291
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 26/04/2002
Date of latest renewal: 26/04/2007
10 DATE OF REVISION OF THE TEXT
23/12/2015
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