1. Name Of The Medicinal Product
Nicorette Microtab Lemon 2 mg sublingual tablets.
2. Qualitative And Quantitative Composition
Nicotine bitartrate equivalent to 2.0 mg nicotine per tablet.
Nicotine Microtab Lemon also contains the ingredient aspartame. Please see section 4.4.
For a full list of excipients see section 6.1
3. Pharmaceutical Form
Sublingual tablet.
White to off-white flat round, bevel-edged tablets engraved on one side with 'N2'.
4. Clinical Particulars
4.1 Therapeutic Indications
Nicorette Microtab Lemon 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 also indicated in pregnant and lactating women (see section 4.6).
In smokers currently unable or not ready to stop smoking abruptly, Nicorette Microtab Lemon may also be used as part of a programme to reduce smoking prior to stopping completely.
If possible, Nicorette Microtab Lemon should be used in conjunction with a behavioural support programme.
4.2 Posology And Method Of Administration
Behavioural therapy, advice and support will normally improve the success rate.
Smoking cessation
Adults (over 18 years of age)
The patient should make every effort to stop smoking completely during treatment with Nicorette Microtab Lemon.
The initial dose is based on the individual's nicotine dependence. The tablet is used sublingually with a recommended dose of one tablet per hour or, for heavy smokers (smoking more than 20 cigarettes per day), two tablets per hour. Increasing to two tablets per hour may be considered for patients who fail to stop smoking with the one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.
Most smokers require 8 to 12 or 16 to 24 tablets per day, not to exceed 40 tablets. The duration of treatment depends on the individual, but up to three months of treatment is recommended. The nicotine dose should then be gradually reduced, by decreasing the total number of tablets used per day. The treatment should be stopped when the daily consumption is down to one or two tablets.
Adults who use nicotine replacement therapy (NRT) beyond 9 months 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 Microtab Lemon.
The initial dose is based on the individual's nicotine dependence. The tablet is used sublingually with a recommended dose of one tablet per hour or, for heavy smokers (smoking more than 20 cigarettes per day), two tablets per hour. Increasing to two tablets per hour may be considered for patients who fail to stop smoking with the one tablet-per-hour regimen or for those whose nicotine withdrawal symptoms remain so strong as to foresee a relapse.
Most smokers require 8 to 12 or 16 to 24 tablets per day, not to exceed 40 tablets. Use for up to 8 weeks to break the habit of smoking, then gradually reduce the dose over a 4 week period. The treatment should be stopped when the daily consumption is down to one or two tablets. 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.
Children (under 12 years)
There is no relevant indication for the use of Nicorette Microtab Lemon in children under 12.
Smoking reduction
Adults (over 18 years of age)
Use Nicorette Microtab Lemon between smoking episodes to manage the urge to smoke, to prolong smoke-free intervals and with the intention to reduce smoking as much as possible. If a reduction in number of cigarettes per day has not been achieved after 6 weeks, professional advice should be sought.
A quit attempt should be made as soon as the smoker feels ready, but not later than 6 months after start of treatment. If a quit attempt cannot be made within 9 months after starting treatment, professional advice should be sought.
When making a quit attempt the smoking cessation instructions above can be followed.
Adolescents (12 to 18 years)
Where adolescents are motivated to stop smoking abruptly, smoking cessation should be recommended. However, smoking reduction can be considered where adolescents are not ready or able to stop smoking abruptly. As data are limited in this age group, and the recommended duration of NRT is 12 weeks, adolescents should consult a healthcare professional before starting the “smoking reduction prior to stopping” regimen.
Use Nicorette Microtab Lemon between smoking episodes to manage the urge to smoke, to prolong smoke-free intervals and with the intention to reduce smoking as much as possible. If a reduction in number of cigarettes per day has not been achieved after 6 weeks, professional advice should be sought.
A quit attempt should be made as soon as the smoker feels ready, but not later than 6 months after start of treatment. If a quit attempt cannot be made within 9 months after starting treatment, professional advice should be sought.
When making a quit attempt the smoking cessation instructions for adolescents (12 to 18 years) given above can be followed.
Children (under 12 years)
There is no relevant indication for the use of Nicorette Microtab Lemon in children under 12.
4.3 Contraindications
Hypersensitivity to nicotine or any other component of the sublingual tablet.
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.
Nicorette Microtab Lemon contains the ingredient aspartame which is a source of phenylalanine and may be harmful for people with phenylketonuria.
Underlying cardiovascular disease: In stable cardiovascular disease Nicorette Microtab Lemon 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 Microtab 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.
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.
Renal or hepatic impairment: Nicorette Microtab Lemon 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.
Phaeochromocytoma and uncontrolled hyperthyroidism: As nicotine causes release of catecholamines, Nicorette Microtab Lemon 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: See section 4.5
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 i.e. increase in blood pressure and heart rate and also increase pain response (angina-pectoris type chest pain) provoked by adenosine administration.
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.
4.6 Pregnancy And Lactation
Pregnancy
NRT is not contraindicated in pregnancy. The decision to use NRT should be made on a risk-benefit assessment as early on in the pregnancy as possible with the aim of discontinuing use as soon as possible.
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 to assist a quit attempt.
Nicotine passes to the foetus affecting breathing movements and has a dose-dependent effect on placental/foetal circulation. However the risk of using NRT to the foetus 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.
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. If patches are used they should be removed before going to bed.
Lactation
NRT is not contraindicated in lactation. Nicotine from smoking and NRT is found in breast milk. However the amount of nicotine the infant is exposed to is relatively small and less hazardous than the second-hand smoke they would otherwise be exposed.
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 more easily prolonged.
4.7 Effects On Ability To Drive And Use Machines
This medicinal product has no or negligible influence on the ability to drive and use machines.
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 Microtab Lemon 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 Microtab Lemon has not been found to cause any serious adverse effects. Excessive consumption of Nicorette Microtab Lemon by those who have not been in the habit of inhaling tobacco smoke could possibly lead to nausea, faintness or headaches.
Most of the undesirable effects associated with Nicorette Microtab Lemon occur during the first 3-4 weeks after starting treatment.
Reported adverse events associated with Nicorette Microtab Lemon 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.
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: Drug for treatment of addiction
ATC code: N07B A01
The pharmacological effects of nicotine are well documented. Those resulting from using Nicorette Microtab Lemon are comparatively small. The response at any one time represents a summation of stimulant and depression actions from direct, reflex and chemical mediator influences on several organs. The principal 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.
5.2 Pharmacokinetic Properties
The amount of nicotine absorbed from a nicotine sublingual tablet depends on the amount of nicotine released in the oral cavity and the amount thereof that is swallowed. Most of the absorption of nicotine from Nicorette Microtab Lemon occurs directly through the buccal mucosa. The absolute bioavailability, after sublingual administration of the tablet, is approximately 50%. The systemic bioavailability of swallowed nicotine is lower due to the amount removed initially by the liver (the first-pass effect). Hence, the high and rapidly rising nicotine concentrations seen after smoking are rarely produced by treatment with nicotine sublingual tablets.
Steady-state trough nicotine plasma concentrations, achieved after ten hourly doses of one tablet, are in the order of magnitude of 10 ng/mL, which is about 50% of normal smoking levels.
There is a slight deviation from dose-linearity of AUCinf and Cmax when single doses of one, two and three tablets are given. This deviation may be explained by a larger fraction of the higher doses being swallowed and subject to first-pass elimination.
The volume of distribution following i.v. administration of nicotine is about 2 to 3 l/kg. 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 major eliminating organ is the liver, and average plasma clearance is about 70 l/hour and the half-life approximately 2 hours. 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.
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 (15% of the dose) and trans-3-hydroxy-cotinine (45% of the dose). About 10% of nicotine is excreted unchanged in the urine. As much as 30% of nicotine may be excreted unchanged in the urine with high flow rates and acidification of the urine below pH 5.
Renal impairment
Progressive severity of renal impairment is associated with decreased total clearance of nicotine. Nicotine clearance was decreased by on average 50% in subjects with severe renal impairment. Raised nicotine levels have been seen in smoking patients undergoing haemodialysis.
Hepatic impairment
The pharmacokinetics of nicotine are unaffected in cirrhotic patients with mild liver impairment (Child-Pugh score 5) and decreased by 40-50% in cirrhotic patients with moderate liver impairment (Child-Pugh score 7). There is no information available in subjects with a Child-Pugh score>7.
5.3 Preclinical Safety Data
Preclinical data indicate that nicotine is neither mutagenic or genotoxic.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Mannitol (E421)
Microcrystalline cellulose
Povidone
Methylcellulose
Silicified microcrystalline cellulose
Magnesium stearate
Lemon flavour
Aspartame (E951)
Flavour
6.2 Incompatibilities
Not applicable.
6.3 Shelf Life
36 months
6.4 Special Precautions For Storage
Do not store above 25ºC.
6.5 Nature And Contents Of Container
Pack sizes
Cardboard box of 30 and 100 sublingual tablets with a package insert/booklet.
AL/AL blister strips of 10 sublingual tablets.
Not all pack sizes may be marketed.
6.6 Special Precautions For Disposal And Other Handling
Any unused product or waste material should be disposed of in accordance with local requirements.
7. Marketing Authorisation Holder
McNeil Products Limited
Foundation Park
Roxborough Way
Maidenhead
Berkshire
SL6 3UG
UK
8. Marketing Authorisation Number(S)
PL 15513/0156
9. Date Of First Authorisation/Renewal Of The Authorisation
30th June 2009
10. Date Of Revision Of The Text
30th June 2009
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