SEREVENT™ Inhaler
Salmeterol Inhaler (25 micrograms per metered actuation)
Qualitative and quantitative composition
SEREVENT Inhaler consists of a white microfine suspension of salmeterol as salmeterol xinafoate (salmeterol hydroxynaphthoate) in a chlorofluorohydrocarbon liquid propellant mixture packed under its own vapour pressure in an aluminium can which is sealed with a metering valve.
SEREVENT Inhaler is a pressurised metered-dose inhaler delivering 25 micrograms salmeterol with each actuation.
Each canister provides 120 actuations.
Pharmaceutical Form
Aerosol.
Clinical Particulars
Therapeutic indications
SEREVENT, as twice-daily regular treatment, can replace a short-acting (4 hour) inhaled bronchodilator (e.g. salbutamol), when it is required more than once a day, or an oral bronchodilator (e.g. salbutamol, theophylline). However, SEREVENT is not a replacement for oral or inhaled steroids, its use is complementary to them. Patients must be warned not to stop steroid therapy or reduce it without medical advice, even if they feel better on SEREVENT.
Bronchodilators should not be the only or the main treatment in patients with severe or unstable asthma. Severe asthma requires regular medical assessment as death may occur. Patients with severe asthma have constant symptoms and frequent exacerbations, with limited physical capacity, and PEF values below 60% predicted at baseline with greater than 30% variability, usually not returning entirely to normal after a bronchodilator. These patients will require high dose inhaled (e.g. >1mg/day beclomethasone dipropionate) or oral corticosteroid therapy. With optimal background steroid therapy, SEREVENT can offer additional symptomatic treatment. Sudden worsening of symptoms may require increased corticosteroid dosage which should be administered under urgent medical supervision.
Adults:-
SEREVENT provides long-lasting (12 hour) bronchodilatation in reversible airways obstruction due to asthma, chronic obstructive pulmonary disease (COPD) and chronic bronchitis. It is suitable for long-term regular twice-daily treatment to control symptoms, but in view of its slower onset of action (10 to 20 minutes) it should not be used to relieve acute asthmatic symptoms, for which a faster acting (within 5 minutes) inhaled bronchodilator (e.g. salbutamol) should be given.
SEREVENT is indicated when regular bronchodilator is required, and to prevent night-time symptoms and/or day-time fluctuations caused by reversible obstructive airways disease (e.g. before exercise or unavoidable allergen challenge).
There is no evidence that SEREVENT is a replacement for corticosteroid treatment of asthma and this should not be stopped or reduced when SEREVENT is prescribed. In patients not already receiving anti-inflammatory therapy, this should be considered when starting SEREVENT.
Children:-
Regular treatment of reversible airways obstruction in asthma including long lasting prevention of exercise-induced bronchospasm.
Posology and Method of Administration
SEREVENT is administered by the inhaled route only.
It is intended that each prescribed dose is given by a minimum of 2 inhalations.
In order to gain full therapeutic benefit regular usage of SEREVENT is recommended in the treatment of reversible airways obstruction due to asthma, COPD and chronic bronchitis. The onset of effective bronchodilation (>15% improvement in FEV 1) occurs within 10 to 20 minutes in asthma patients. The full benefits will be apparent after the first few doses of the drug. The bronchodilator effects of SEREVENT usually last for 12 hours. This is particularly useful in the treatment of nocturnal symptoms in asthma, COPD and chronic bronchitis and in the management of exercise induced asthma.
Patients should be instructed not to take additional doses to treat symptoms but to take a short-acting inhaled β2 agonist.
In patients who find co-ordination of a pressurised metered-dose inhaler difficult a Volumatic spacer may be used with SEREVENT Inhaler.
As there may be adverse effects associated with excessive dosing of this class of drug, the dosage of frequency of administration should only be increased on medical advice.
Adults:-
Treatment of asthma, COPD and chronic bronchitis.
Two inhalations (2 x 25mcg of salmeterol) twice daily.
In asthma patients with more severe airways obstruction up to four inhalations (4 x 25mcg of salmeterol) twice daily may be of benefit.
Children over 4 years of age:-
Two inhalations (2 x 25mcg of salmeterol) twice daily.
There are insufficient clinical data at present to recommend the use of SEREVENT in children under 4 years of age.
Special patient groups.
There is no need to adjust the dose in elderly patients or in those with renal impairment.
Contraindications
Hypersensitivity to any ingredient of the preparation.
Special warnings and special precautions for use
The management of asthma should normally follow a stepwise programme, and patient response should be monitored clinically and by lung function tests.
SEREVENT should not be initiated in patients with significantly worsening or acutely deteriorating asthma.
Sudden and progressive deterioration of asthma is potentially life threatening and considerations should be given to starting or increasing corticosteroid therapy. In patients at risk, daily peak flow monitoring may be instituted.
Bronchodilators should not be the only or the main treatment in patients with severe or unstable asthma. Severe asthma requires regular medical assessment, including lung function testing, as patients are at risk of severe attacks and even death. Physicians should consider using oral corticosteroid therapy and/or maximum recommended dose of inhaled corticosteroid in these patients.
Increasing use of bronchodilators, in particular short-acting inhaled β 2 agonists, to relieve symptoms indicates deterioration of asthma control. If patients find that short-acting relief bronchodilator treatment becomes less effective or they need more inhalations than usual, medical attention must be sought. In this situation patients should be reassessed and consideration given to the need for increased anti- inflammatory therapy (e.g. higher doses of inhaled corticosteroids or a course of oral corticosteroids). Severe exacerbations of asthma must be treated in the normal way.
SEREVENT is not a replacement for oral or inhaled corticosteroids. Its use is complementary to them. Patients must be warned not to stop steroid therapy and not to reduce it without medical advice even if they feel better on SEREVENT.
SEREVENT is not designed to relieve acute asthma symptoms, for which an inhaled short-acting bronchodilator (e.g. salbutamol) is required.
Patients should be advised to have such relief medication available.
Patients' inhaler technique should be checked to make sure that aerosol actuation is synchronised with inspiration of breath for optimum delivery of the drug to the lungs.
SEREVENT should be administered with caution in patients with thyrotoxicosis.
Use during Pregnancy and lactation
In animal studies, some effects on the foetus, typical for a β 2 agonist, occurred at exposure levels substantially higher than those that occur with therapeutic use. Extensive experience with other β2 agonists has provided no evidence that such effects are relevant for women receiving clinical doses.
As yet, experience of the use of salmeterol during pregnancy is limited.
As with any medicine, use during pregnancy should be considered only if the expected benefit to the mother is greater than any possible risk to the foetus.
Plasma levels of salmeterol after inhaled therapeutic doses are negligible and therefore levels in milk should be correspondingly low. Nevertheless as there is limited experience of the use of salmeterol in nursing mothers its use in such circumstances should only be considered if the expected benefit to the mother is greater than any possible risk to the infant.
Studies in lactating animals support the view that salmeterol is likely to be secreted in only very small amounts into breast milk.
Effects on the ability to drive and operate machinery
None reported.
Interaction with other medicaments and other forms of interaction
Both non-selective and selective β-blockers should be avoided in patients with reversible obstructive airways disease, unless there are compelling reasons for their use.
Undesirable effects
The pharmacological side-effects of β 2 agonist treatment, such as tremor, subjective palpitations and headache, have been reported, but tend to be transient and to reduce with regular therapy. Cardiac arrhythmias (including atrial fibrillation, supraventricular tachycardia and extrasystoles) may occur, usually in susceptible patients.
Tachycardia may occur in some patients.
As with other inhalational therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator. SEREVENT Inhaler should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.
There have been reports of arthralgia and hypersensitivity reactions, including rash oedema and angioedema. There have been reports of oropharyngeal irritation. There have been very rare reports of muscle cramps.
Overdose
The symptoms and signs of salmeterol overdosage are tremor, headache and tachycardia. The preferred antidote for overdosage with SEREVENT Inhaler is a cardioselectiv e β-blocking agent. Cardioselective β-blocking drugs should be used with caution in patients with history of bronchospasm.
Pharmacological Properties
Pharmacodynamic properties
Mechanism of action.
Salmeterol is a selective long-acting (12 hour) β 2 adrenoceptor agonist with a long side-chain which binds to the exo-site of the receptor.
These pharmacological properties of salmeterol offer more effective protection against histamine-induced bronchoconstriction and produce a longer duration of bronchodilation, lasting for at least 12 hours, than recommended doses of conventional short-acting β2 agonists. In vitro tests have shown salmeterol is a potent and long-lasting inhibitor of the release, from human lung, of mast cell mediators, such as histamine, leukotrienes and prostaglandin D2. In man salmeterol inhibits the early and late phase response to inhaled allergen; the latter persisting for over 30 hours after a single dose when the bronchodilator effect is no longer evident. Single dosing with salmeterol attenuates bronchial hyper-responsiveness. These properties indicate that SEREVENT has additional non-bronchodilator activity, but the full clinical significance is not yet clear. The mechanism is different from the anti-inflammatory effect of corticosteroids, which should not be stopped or reduced when SEREVENT is prescribed.
SEREVENT has been studied in the treatment of conditions associated with COPD and has been shown to improve symptoms and pulmonary function, and quality of life. Salmeterol acts as a β 2 agonist on the reversible component of the disease. In vitro salmeterol has also been shown to increase cilial beat frequency of human bronchial epithelial cells, and also reduce acidiotoxic effect of Pseudomonas toxin on the bronchial epithelium of patients with cystic fibrosis.
Pharmacokinetic properties
SEREVENT acts locally in the lung therefore plasma levels are not predicative of therapeutic effect. In addition there are only limited data available on the pharmacokinetics of salmeterol because of the technical difficulty of assaying the drug in plasma because of the very low plasma concentrations (approximately 200pg/mL or less) achieved after inhaled dosing. After regular dosing with SEREVENT xinafoate, hydroxynaphthoic acid can be detected in the systemic circulation, reaching steady state concentrations of approximately 100ng/mL. These concentrations are up to 1000 fold lower than steady state levels observed in toxicity studies and in long term regular dosing (more than 12 months) in patients with airways obstruction, have been shown to produce no ill effects.
Preclinical safety data
In reproduction studies in animals, some effects on the foetus, typical of a β 2 agonist, have been observed at very high doses.
Salmeterol xinafoate produced no genetic toxicity in a range of studies using either prokaryotic or eukaryotic cell systems in vitro or in vivo in the rat.
Long term studies with salmeterol xinafoate, induced class related benign tumours of smooth muscle in the mesovarium of rats and the uterus of mice.
The scientific literature and our own pharmacological studies provide good evidence that these effects are species specific and have no relevance for clinical use.
Pharmaceutical Particulars
List of excipients
Lecithin.
Dichlorodifluoromethane.
Trichlorofluoromethane.
Incompatibilities
None reported.
Shelf life
2 years below 30°C.
Special storage precautions
SEREVENT Inhaler should be stored below 30°C.
Protect from frost and direct sunlight.
As with most inhaled medications in pressurised metered-dose inhalers, the therapeutic effect of this medication may decrease when the canister is cold.
The canister should not be broken, punctured or burnt, even when apparently empty.
Nature and contents of container
SEREVENT Inhaler is a pressurised metered-dose inhaler with a specially designed actuator. The container is an aluminium alloy canister fitted with a metering valve. Each canister provides 120 actuations.
Further information
SEREVENT Inhaler is included in the Intensive Medicines Monitoring Programme.
Instructions for use/handling
Remove the mouthpiece cover by gently squeezing the sides of the cover and check the mouthpiece inside and outside to see that it is clean.
Shake the inhaler well.
Hold the inhaler upright between fingers and thumb with your thumb on the base, below the mouthpiece.
Breathe out as far as is comfortable and then place the mouthpiece in your mouth between your teeth and close your lips around it but do not bite it.
Just after starting to breathe in through your mouth press down on the top of the inhaler to release SEREVENT while still breathing in steadily and deeply.
While holding your breath, take the inhaler from your mouth and take your finger from the top of the inhaler. Continue holding your breath for as long as is comfortable.
If you are to take a further puff keep the inhaler upright and wait about half a minute before repeating steps 2 to 6.
After use always replace the mouthpiece cover to keep out dust and fluff.
The mouthpiece cover is replaced by firmly pushing and snapping the cap into position.
IMPORTANT:-
Do not rush stages 4, 5 and 6. It is important that you start to breathe in as slowly as possible just before operating your inhaler.
Practise in front of a mirror for the first few times. If you see "mist" coming from the top of your inhaler or the sides of your mouth you should start again from stage 2.
If your doctor has given you different instructions for using your inhaler, please follow them carefully. Tell your doctor if you have any difficulties.
CHILDREN:-
Young children may need help and their parents may need to operate the inhaler for them. Encourage the child to breathe out and operate the inhaler just after the child starts to breathe in. Practice the technique together. Older children or people with weak hands should hold the inhaler with both hands. Put the two forefingers on top of the inhaler and both thumbs on the base below the mouthpiece.
Cleaning:-
Your inhaler should be cleaned at least once a week.
- Pull the metal canister out of the plastic casing of the inhaler and remove the mouthpiece cover.
- Rinse the plastic casing and mouthpiece cover in warm water.
- Leave them to dry in a warm place. Avoid excessive heat.
- Replace the canister and mouthpiece cover.
A mild detergent or a solution of the type used to clean babies feeding bottles may be added to the water (your pharmacist will advise you). Then rinse thoroughly with clean water before drying. DO NOT PUT THE METAL CANISTER INTO WATER.
Testing your inhaler:-
If your inhaler has not been used for a week or more release one puff into the air to make sure that it works.
Medicine Classification
Prescription Only Medicine
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