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NICORETTE INHALER (Inhaler with cartridges)

SCHEDULING STATUS:
S2

PROPRIETARY NAME
(and dosage form):

NICORETTE INHALER (Inhaler with cartridges)

COMPOSITION:
Inhalation vapour, liquid, 10 mg nicotine per cartridge.

PHARMACOLOGICAL CLASSIFICATION:
A 34 Other

PHARMACOLOGICAL ACTION:
Pharmacokinetic Properties:
Plasma binding of nicotine is below 5%. Nicotine is excreted in the urine principally as cotinine (15%), 3-hydroxycotinine (45%), nicotine (10%).
Most inhaled nicotine from the NICORETTE INHALER is absorbed via the buccal mucosa. Forced rapid inhalation over 20 minutes will remove 40% of the nicotine from the cartridge. Uptake is slow and free of the peaks seen with cigarette smoking. In normal use, plasma levels of 6 - 8 ng/mL nicotine are obtained - about one third that from smoking, and equivalent to an hourly 2 mg nicotine chewing gum.
Peak plasma levels occur within 15 minutes after the end of inhalation of the contents of a cartridge. Forced rapid inhalation for 20 minutes per hour for 12 hours achieved steady state plasma levels of 20 - 25 ng/mL.
Ambient temperature affects volatilisation of nicotine, the biologically available dose rising by 35% for each 10°C above 20°C. Use below 15°C is not recommended.

INDICATIONS:
NICORETTE is indicated as a temporary aid to the cigarette smoker seeking to give up his or her smoking habit while participating in a behavioural modification programme under professional supervision. The efficacy of NICORETTE use without concomitant participation in a behavioural modification programme has not been established.

CONTRA-INDICATIONS:
NICORETTE is contra-indicated in non-tobacco users or patients known to be intolerant of nicotine or menthol.
NICORETTE is contra-indicated in patients during the immediate post-myocardial infarction period, in patients with life-threatening arrhythmias and patients with severe or worsening angina pectoris. NICORETTE is also contra-indicated in patients with active temporomandibular joint disease.

WARNINGS:
The risks of nicotine in patients with severe cardiovascular diseases should be carefully weighed against the benefits of including NICORETTE in a smoking cessation programme in these patients. Specifically, patients with coronary heart disease (such as myocardial infarction in the last 3 months and/or unstable angina pectoris), serious cardiac arrhythmias or vasospastic diseases (Buerger’s disease, Prinzmetal variant angina) should be carefully screened and evaluated before NICORETTE is prescribed.
As the action of nicotine on the adrenal medulla (release of catecholamines) does not appear to be affected by tolerance, NICORETTE should be used with caution in patients with endocrine disorders including hyperthyroidism, phaeochromocytoma or insulin-dependent diabetes.
Cigarette smoking is felt to play a perpetuating role in hypertension and peptic ulcer disease. Therefore, NICORETTE should be used in patients with systemic hypertension or inactive peptic ulcer only when the benefits of including NICORETTE in a smoking cessation programme outweigh the risks.
Allergic reactions, such as angioedema, urticaria and ulcerative stomatitis have been reported
Pregnancy:
NICORETTE may cause foetal harm when administered to a pregnant woman. NICORETTE is therefore contra-indicated in women who are or may become pregnant, and female patients should be advised to take adequate precautions to avoid becoming pregnant. The doctor may wish to consider a pregnancy test before instituting therapy with NICORETTE. If NICORETTE is used during pregnancy, or if the patient becomes pregnant while taking NICORETTE, the patient should be apprised of the potential hazard to the foetus.
Breastfeeding:
Nicotine passes freely into breast-milk in quantities that may affect the infant and therefore should not be used by nursing mothers.
Paediatric Use:
NICORETTE should not be given to children.

DOSAGE AND DIRECTIONS FOR USE:
Adults (including elderly):
The frequency should depend on the previous smoking habit of the individual. NICORETTE INHALER should be used whenever the urge to smoke is felt, up to a maximum usage of 12 cartridges per day.
In the treatment of nicotine dependence, a course not exceeding 6 months is suggested, the patient stopping smoking completely at the start of the course. Efficacy of NICORETTE INHALER beyond 6 months has not been established.

a)	For up to 3 months the patient uses the contents of between 6 and a maximum of 12 cartridges each day, to relieve craving.
b)	Over the following 3 months the aim is to reduce the number of cartridges gradually, to reduce the number to zero by the last day.
c)	Counselling and support from family, friends and health professionals can improve the chances of abstinence.
d)	Patients who revert to smoking during or upon completion of the course should see a doctor before attempting a new course. Similarly, where a course extends into chronic use because of inability to cut down use of the Inhaler, medical advice should be sought.

Method of administration:
The cartridge is inserted into the mouthpiece according to the instructions. The patient draws air into the mouth through the mouthpiece: there is a greater effort needed than with a cigarette. The patient may find deep drawing or short sucks on the mouthpiece most effective - patients soon find a favoured technique. Nicotine vapour passing through the mouth is absorbed by the buccal mucosa: little reaches the lungs. After about 20 minutes of intense use the maximal dose is achieved and it is then that the nicotine amounts released from the cartridge begin to fall away, such that the cartridge is rejected by the user.
The actual time that the cartridge is active depends on the intensity of use.
Instruction for use/handling:

1.	Remove the aluminium foil sealed tray and the mouthpiece from the carton.
2.	Peel back the foil from the tray.
3.	Pull the mouthpiece apart and insert a cartridge, whereby the seal of the inserted end of the cartridge is perforated.
4.	Push the other part of the mouthpiece back into place over the cartridge; the product is ready for use.
5.	Grip the mouthpiece with the lips.

As air is inhaled, the nicotine is vapourised and absorbed in the mouth.
Disposal instructions:
Because of residual nicotine, used cartridges may be a hazard to children, animals and fish and so should never be thrown away or left lying around. They should be kept in the carton and disposed of with household rubbish.
Cleaning of mouthpiece:
The empty mouthpiece should be rinsed in water several times a week.
NICORETTE INHALER should be used when the patient has the urge for a cigarette or feels the onset of other withdrawal symptoms, up to a maximum of twelve cartridges per day.
The number, frequency, puffing/inhalation time and technique vary individually. Studies show that different inhalation techniques give similar effects: deep inhalation (the cigarette smoker’s way) or shallow puffing (the pipe smoker’s way). The amount of nicotine from a puff is less than that from a cigarette.
To compensate for less nicotine delivery from a puff, it is necessary to inhale more often than when smoking a cigarette, i.e. use the NICORETTE INHALER for longer periods at a time. After using a few cartridges the patient will have found a method that suits him/her and gives the best effect.
The product works best at room temperature. In cold conditions (below 15°C) the nicotine evaporates less rapidly and it will be necessary to inhale more frequently, whilst in warm conditions (above 30°C) nicotine will evaporate more readily and inhalation should be less frequent to avoid overdose.
Children:
NICORETTE INHALER should not to be administered to children under 18 years of age.
Concomitant disease:
Only severe renal impairment would be expected to affect the clearance of nicotine or its metabolites from the circulation. In patients smoking and undergoing haemodialysis, elevated nicotine levels have been seen.
Patients with obstructive lung disease may find use of the Inhaler difficult. Nicotine gum or patches may be preferred in such cases.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
The patient should stop smoking or using other sources of nicotine completely when initiating therapy with the product. Patients who continue smoking or use other sources of nicotine when using the NICORETTE INHALER may experience adverse effects due to peak nicotine levels higher than those experienced from smoking alone.
The most frequent reported adverse events are local i.e. cough and irritation in the mouth and throat. The following adverse events were reported in clinical trials in decreasing order of frequency: cough, headache, throat irritation, rhinitis, pharyngitis, stomatitis, dyspepsia, anxiety, nausea, sinusitis, dry mouth, chest pain, skeletal pain, diarrhoea, flatulence, local parasthesis, allergy, depression, vomiting, dyspnoea, thirst, gingival irritation and hiccup.
Some symptoms, such as dizziness, headache and sleeplessness, may be related to withdrawal symptoms associated with smoking cessation. Increased frequency of aphthous ulcer may occur after smoking cessation. The causality is unclear. Maintained nicotine dependence may occur.
Drug Interactions:
Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking is considered to increase metabolism and thus lower blood levels of drugs such as phenacetin, caffeine, theophylline, imipramine and pentazocine, through enzyme induction. Cessation of smoking may result in increased levels of these drugs. Absorption of glutethimide may be decreased and the “first pass” metabolism of propoxyphene decreased by smoking cessation. Other reported effects of smoking, which do not involve enzyme induction, include reduced diuretic effects of furosemide and decreased cardiac output, and increased blood pressure with propranolol, which may also relate to the hormonal effects of nicotine. Smoking cessation may reverse these actions.
Both smoking and nicotine can increase circulating cortisol and catecholamines. Therapy with adrenergic agonists or with adrenergic blockers may need to be adjusted according to changes in nicotine therapy or smoking status.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Overdosage with nicotine can occur if the patient has very low nicotine dependence or uses other forms of nicotine concomitantly. During non-clinical forced inhalation techniques, maximum plasma levels produced were in the range found when smoking.
Symptoms of overdosage include nausea, salivation, abdominal pain, vomiting, diarrhoea, sweating, headache, dizziness, disturbed hearing and marked weakness. Faintness and prostration may ensue and hypotension may occur, breathing is difficult, the pulse may be rapid, weak and irregular. Collapse may be followed by terminal convulsions. Death may result within a few minutes from respiratory failure caused by paralysis of the muscles of respiration.
The minimum lethal oral dose of nicotine for adults is reported to be 40 to 60 mg.
Nicotine is excreted four times more rapidly in acid than alkaline urine.
Artificial respiration with oxygen should be instituted if needed and continued for as long as necessary.
Other therapy, including treatment of shock, is purely symptomatic.

IDENTIFICATION:
White to slightly coloured porous plugs in sealed, transparent plastic tubes

PRESENTATION:
3x6 cartridges in a blister tray + plastic mouthpiece + a package insert.

STORAGE INSTRUCTIONS:
Store at room temperature below 25°C. Do not refrigerate.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBER:
34/34/0329

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Pharmacia South Africa (Pty) Ltd
Alphen West G
George Street
MIDRAND
1685
RSA

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
8 May 2000

New addition to this site: February 2005
Source: Pharmaceutical Industry
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