Nicabate Mini 1.5 Mg Compressed Lozenges
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Nicabate Mini 1.5 mg Compressed Lozenges
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each lozenge contains 1.5 mg nicotine (as nicotine resinate).
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Compressed Lozenge (lozenge)
White to off white oval lozenge with convex surfaces; one surface bearing a debossed “L” logo.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Nicabate Minis 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.
Nicabate Minis should preferably be used in conjunction with a behavioural support programme.
4.2 Posology and method of administration Directions for use:
The strength of lozenge to be used will depend on the smoking habits of the individual.
Nicabate Minis 1.5 mg are suitable for smokers who smoke 20 cigarettes or less a day.
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 10 minutes). The lozenge should not be chewed or swallowed whole.
Users should not eat or drink while a lozenge is in the mouth.
Behavioural therapy advice and support will normally improve the success rate.
Adults
Users should make every effort to stop smoking completely during treatment with Nicabate Minis.
Use the lozenges whenever there is an urge to smoke.
Sufficient lozenges should be used each day, usually 8-12, up to a maximum of 15.
Continue use for up to six weeks to break the habit of smoking, then gradually reduce lozenge use. When daily use is 1-2 lozenges, use should be stopped.
To help stay smoke free after treatment, users may take a lozenge in situations when they are strongly tempted to smoke.
Those who use lozenges beyond 9 months are recommended to seek additional help and advice from a healthcare professional.
Children and adolescents:
Nicabate Minis should only be used by adolescents (12-17 years inclusive) with advice from a healthcare professional.
Nicabate Minis are not recommended for use in children below the age of 12 due to a lack of data on safety and efficacy.
4.3 Contraindications
• people with hypersensitivity to nicotine or any of the excipients;
• children under the age of 12 years
• non-smokers.
4.4 Special warnings and precautions for use
The risks associated with the use of nicotine replacement therapy (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 arrhythmias, uncontrolled hypertensions or recent cerebrovascular accident should be encouraged to stop smoking with non-pharmacological interventions (such as counselling). If this fails, Nicabate Minis may be considered but as data on safety in this patient group are limited, initiation should only be under close 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.
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.
• Gastrointestinal Disease: Swallowed nicotine may exacerbate symptoms in patients suffering from oesophagitis, gastric or peptic ulcers 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.
During a quit attempt users should not interchange Nicabate Minis with nicotine gums since pharmacokinetic data indicate a higher availability of nicotine from Nicabate Minis in comparison to the gum.
4.5. Interaction with other medicinal products and other forms of interaction
No clinically relevant interactions between nicotine replacement therapy and other medicinal products 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 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.
Lactation
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 lactation 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.
4.7 Effects on ability to drive and use machines
There are no known effects of Nicabate Minis 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, some of which are dose dependent. At recommended doses Nicabate Minis have not been found to cause any serious adverse effects. Excessive consumption of Nicabate Minis by those who have not been in the habit of inhaling tobacco smoke could possible lead to nausea, faintness or headaches.
Certain symptoms which have been reported such as depression, irritability, anxiety, increased appetite 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, sleep disturbance, increased coughing or a cold.
Immune System Disorder
Very rare <1/10000: anaphylactic reactions
Psychiatric disorders
Common (>1/100 to <1/10): irritability, anxiety, sleep disorders incl. abnormal dreams
Uncommon (>1/1000 to <1/100): nervousness, depression Nervous system disorders:
Common (>1/100 to <1/10): dizziness, headaches Cardiac Disorders
Uncommon (>1/1000 to <1/100): palpitations, heart rate increased Respiratory, thoracic and mediastinal disorders
Common (>1/100 to <1/10): cough, sore throat Gastrointestinal disorders
Very common (>1/10): nausea, mouth/throat and tongue irritation
Common (>1/100 to <1/10): vomiting, diarrhoea, gastro-intestinal discomfort, flatulence, hiccups, heartburn, dyspepsia
Skin and Subcutaneous Tissue Disorders
Uncommon (>1/1000 to <1/100): rash General Disorders and Administration Site Conditions
Uncommon (>1/1000 to <1/100): fatigue, malaise, chest pain
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: N07B A01
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 lozenges 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
Nicabate Minis dissolve completely 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 Minis is typically achieved in 10 minutes. When dosed every hour, the steady state mean cmax and cmin concentrations are 18.4 and 15.0 ng/ml respectively.
As the plasma protein binding of nicotine is low (4.9%), 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.
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.
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 Nicabate Minis. Effects on fertility have not been established.
Comparison of the systemic exposure necessary to elicit these adverse responses from preclinical test systems with that associated with the recommended use of Nicabate Minis indicate that the potential risk is low and outweighed by the demonstrable benefit of nicotine therapy in smoking cessation. However, Nicabate Minis should only be used by pregnant women on medical advice if other forms of treatment have failed.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Mannitol (E421)
Sodium alginate Xanthan gum Potassium bicarbonate Calcium polycarbophil Sodium carbonate anhydrous Acesulfame potassium Taste Masking Flavour 031431 Peppermint Flavour 022173 Menthol Flavour 020184 Magnesium Stearate
6.2 Incompatibilities
Not applicable.
6.3. Shelf life
3 years
6.4 Special precautions for storage
Do not store above 30°C. Store in the original package in order to protect the product from moisture.
6.5 Nature and contents of container
Child resistant polypropylene tablet container/cap incorporating a molecular sieve desiccant (sodium aluminosilicate) and containing 20 lozenges
Packs may contain 1 or 3 tablet containers.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements
7 MARKETING AUTHORISATION HOLDER
Beecham Group plc 980 Great West Road Brentford Middlesex TW8 9GS United Kingdom
T/A GlaxoSmithKline Consumer Healthcare Brentford TW8 9GS, UK.
8 MARKETING AUTHORISATION NUMBER(S)
PL 00079/0612
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27/06/2008
10 DATE OF REVISION OF THE TEXT
22/06/2013