Respigen 100 Micrograms Per Actuation Pressurised Inhalation Suspension
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Respigen® 100 micrograms per actuation pressurised inhalation suspension
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Salbutamol (as sulphate) 100 micrograms per metered dose (ex-valve).
For full list of excipients, see Section 6.1.
3 PHARMACEUTICAL FORM
Pressurised inhalation, suspension.
The suspension is delivered via a pressurised metered dose inhaler, consisting of an aluminium canister sealed with a metered dose valve, packed into a blue L-shaped actuator (see also Section 6.5 Nature and contents of container).
This product contains the propellant HFA 134a. It does not contain any chlorofluorocarbons (CFCs).
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Respigen® Inhaler is indicated in adults, adolescents and children aged 4 to 11 years. For babies and children under 4 years of age, see sections 4.2 and 5.1.
Respigen® Inhaler provides short-acting (4 to 6 hours) bronchodilatation with a fast onset of action (within 5 minutes) in reversible airways obstruction.
Respigen® Inhaler is particularly suitable for the relief of asthma symptoms. It should be used to relieve symptoms when they occur and to prevent them in those circumstances recognised by the patient to precipitate an asthma attack (e.g. before exercise or unavoidable allergen exposure).
Respigen® Inhaler is particularly valuable as relief medication in mild, moderate or severe asthma, as long as reliance on it does not delay the introduction and use of regular inhaled corticosteroid therapy.
4.2 Posology and method of administration
Respigen® Inhaler is for oral inhalation use.
Adults (including the elderly):
To relieve acute asthma symptoms, including bronchospasm, one inhalation (100 micrograms) may be taken as a single minimum starting dose. This can be increased to two inhalations if necessary.
To prevent symptoms caused by exercise or allergen exposure two inhalations (200 micrograms) should be taken 10 - 15 minutes before challenge.
For optimum benefit Respigen® Inhaler should be used as required. However, on-demand use of Respigen® Inhaler for the relief of asthma symptoms should not exceed 8 inhalations (equivalent to 800 micrograms) in any 24 hours and 2 inhalations should not usually be repeated more often than every 4 hours (to a maximum dose of 8 inhalations in 24 hours). Reliance on such frequent supplementary use, or a sudden increase in dose indicates poor control of or worsening asthma (see also Section 4.4 Special warnings and precautions for use).
Paediatric population (under the age of 12)
To relieve acute asthma symptoms including bronchospasm, the usual dosage for children under the age of 12 years is one inhalation (100 micrograms); it may be taken as a single minimum (starting) dose. This can be increased to two inhalations if necessary.
To prevent symptoms caused by exercise or by allergen exposure one inhalation (100 micrograms), which may be increased to two if necessary, should be taken 10-15 minutes before challenge.
Children aged 12 years and over: Dose as per adult population.
For optimum benefit Respigen® Inhaler should be used as required. However, on-demand use of Respigen® Inhaler for the relief of asthma symptoms should not exceed 8 inhalations in any 24 hours and 2 inhalations should not usually be repeated more often than every 4 hours (to a maximum dose of 8 inhalations in 24 hours). Reliance on such frequent supplementary use, or a sudden increase in dose indicates poor control of or worsening asthma (see also section 4.4).
Chronic therapy
The usual dosage for children under the age of 12 years: up to two inhalations 4 times daily.
Children aged 12 years and over: Dose as per adult population.
The maximum on-demand use in any 24 hours should not exceed 8 inhalations (equivalent to 800 micrograms). Reliance on such frequent supplementary use, or a sudden increase in dose indicates poor control of or worsening asthma (see also section 4.4).
Instructions For Use
1. The patient should remove the cap from the mouthpiece by holding it between
their thumb and forefinger, squeezing gently whilst pulling them apart. They should check that there are no objects in the mouthpiece and that it is clean.
Testing Respigen® Inhaler
If the inhaler is new, or has not been used for more than one week it should be primed. The patient should be advised to shake it well and fire two puffs into the air to check that it works.
2. The patient should hold the inhaler upright with their thumb on the base and first
finger on the top of the can and should shake the inhaler well.
3. The patient then breathes out slowly through their mouth as far as is comfortable
and then immediately should place the mouthpiece fully into the mouth and should close their lips lightly around it. The patient should be advised not to bite the mouthpiece.
4. The patient should then breathe in slowly and deeply, pressing the metal canister
down firmly with their first finger as they do so to actuate the inhaler. The patient should continue to breathe in steadily and deeply.
5. The patient should hold their breath and remove the mouthpiece from their mouth
and then continue to hold their breath for about 10 seconds, or for as long as is comfortable, before breathing out slowly.
6.
The patient should be advised to wait for about one minute before taking another puff, if needed, by repeating steps 2 to 5 above.
7. The cap should be replaced on the mouthpiece by snapping it into place to protect
the mouthpiece from dirt and dust.
It is VERY important that the patient does not rush steps 3 and 4.
It is also very important that the patient breathes in slowly before pressing the metal canister. The patient can be advised to practise this step in front of a mirror. If mist is seen coming from the mouth or the inhaler then the instructions should be repeated from step 2 above. The patient should however be advised not to have more than 4 goes at this whilst practising.
If the patient has difficulty in operating the inhaler with one hand, it is possible to use both hands. At step 2 both forefingers may be placed on top of the canister and both thumbs on the base. The patient then proceeds as instructed above.
Respigen® Inhaler may be used with the AeroChamber Plus* spacer device by patients who find it difficult to synchronise aerosol actuation with inspiration of breath. This is often the case for children and the elderly.
Respigen® Inhaler should only be used with the AeroChamber Plus* spacer device, it should not be used with any other spacer device as an alternative device may alter the pulmonary deposition of salbutamol.
Detailed instructions for use are also provided with pictograms in the Patient Information Leaflet.
Cleaning
Patients should be advised to clean their inhaler once a week.
1.
The patient should remove the metal canister by gripping it firmly and pulling it out of the actuator. The dust cap should then be removed from the actuator.
2. The patient should clean the mouthpiece and dust cap in warm water. A mild
detergent or baby bottle cleaning solution may be added to the water. If a cleaning solution is used the patient should be advised to rinse the actuator and dust cap in running water. The metal canister should NOT be put into water.
3.
The actuator and dust cap should be placed in a warm place to dry, but direct heat should not be used.
The patient may then replace the dust cap and metal canister by reversing step 1.
Detailed instructions for cleaning are also provided in the Patient Information Leaflet.
4.3 Contraindications
Unlike intravenous salbutamol (and occasionally salbutamol tablets), inhaled salbutamol is not suitable for the treatment of uncomplicated premature labour. Salbutamol should also not be used to treat threatened abortion.
Respigen® Inhaler is contraindicated in patients who are hypersensitive to any of the ingredients.
4.4 Special warnings and precautions for use
Checks should be made on the patients’ inhaler technique to ensure they are synchronising inspiration of breath with actuation for optimum drug delivery to the lungs.
Patients should be informed that Respigen® could taste different when compared with their previous CFC propelled salbutamol inhaler.
Patients with severe or unstable asthma should not be receiving bronchodilator therapy as their main or only treatment. Due to the risk of severe attacks, or even death, patients with severe asthma should be subject to regular medical assessments, including lung function testing. In these patients their doctor should consider the use of the maximum recommended dose of inhaled corticosteroid and/or oral corticosteroid therapy.
Increasing the patient’s dose or the frequency of use of Respigen® should only be carried out on medical advice. The patient must be advised to consult their doctor if they find that their dose of salbutamol is no longer providing relief for at least three hours.
Deterioration of asthma control is indicated by increased use of bronchodilators, especially short-acting inhaled B2-agonists. If the patient notices that their shortacting bronchodilator therapy has become less effective or that they require more inhalations than usual to obtain relief, they must be instructed to seek medical advice. The patient then needs to be assessed with the possible need for increased antiinflammatory therapy (such as increasing the dosage of inhaled corticosteroid or a course of oral corticosteroid).
Severe exacerbations of asthma must be treated in the normal way.
Cardiovascular effects may be seen with sympathomimetic drugs, including salbutamol. There is some evidence from post-marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol. Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving salbutamol should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.
Salbutamol needs to be administered with caution in patients with thyrotoxicosis.
B2-agonist therapy can cause potentially serious hypokalaemia, principally from nebuliser and parenteral administration. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics . Serum potassium levels should be monitored in these situations.
Respigen® Inhaler may also be used with the AeroChamber Plus* spacer device by patients who find it difficult to synchronise aerosol actuation with inspiration of breath. The use of the proposed product with this spacer device may alter the delivery of salbutamol to the lungs and thereby change the systemic absorption of salbutamol. This could potentially lead to an increase in the risk of systemic effects such as hypokalaemia, tremor, tachycardia or cardiac arrhythmias. This possible risk should be highlighted to patients, who should be advised to inform their doctor should any of the symptoms described arise. Dosage adjustment may then be necessary.
Respigen® Inhaler should only be used with the AeroChamber Plus* spacer device, it should not be used with any other spacer device as an alternative device may alter the pulmonary deposition of salbutamol.
4.5 Interaction with other medicinal products and other forms of interaction
Non-selective ^-blocking drugs, such as propranolol, should not normally be prescribed with salbutamol.
4.6 Pregnancy and lactation Respigen® Inhaler
There is no experience with this product in pregnancy and lactation in humans. It should not be used in pregnancy and lactation unless the expected benefit to the mother is thought to outweigh any risk to the fetus or neonate.
Propellant HFA 134a
Studies of propellant HFA 134a administered to pregnant and lactating rats and rabbits have not revealed any special hazard.
Salbutamol
There is little published evidence on the safety of salbutamol in the early stages of human pregnancy. However, in animal studies there was evidence of some harmful effects on the fetus at very high dose levels, in mice and rabbits large doses of salbutamol have been shown to be teratogenic.
As salbutamol is probably secreted in breast milk, its use during lactation requires careful consideration. It is not known whether salbutamol has a harmful effect on the neonate and therefore its use should be restricted to situations where it is felt that the expected benefit to the mother is likely to outweigh any potential risk to the neonate.
4.7 Effects on ability to drive and use machines
No studies on effects on the ability to drive and use machines have been performed. On the basis of the pharmacodynamic profile of salbutamol and the lack of reported relevant adverse drug reactions, salbutamol has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Adverse events are listed below by system organ class and frequency. Frequencies are defined as:
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.
|
Organ System |
Frequency |
Adverse Drug Reaction |
|
Immune system disorders |
Very rare |
Hypersensitivity reactions including angioedema, urticaria, bronchospasm, hypotension and collapse |
|
Metabolism and nutrition disorders |
Rare |
Hypokalaemia. Potentially serious hypokalaemia may result from beta2 agonist therapy |
|
Nervous system disorders |
Common |
Fine skeletal muscle tremor in which the hands are most obviously affected, headache |
|
Rare |
Hyperactivity, particularly in children | |
|
Cardiac disorders |
Common |
Tachycardia |
|
Uncommon |
Palpitations | |
|
Rare |
Myocardial ischaemia (see section 4.4) | |
|
Very rare |
Cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia, extrasystoles | |
|
Vascular disorders |
Rare |
Peripheral vasodilatation |
|
Respiratory, thoracic and |
Very rare |
Paradoxical bronchospasm* |
|
mediastinal disorders | ||
|
Gastrointestinal disorders |
Uncommon |
Mouth and throat irritation |
|
Musculoskeletal and connective tissue disorders |
Uncommon |
Muscle cramps |
*As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing and/or shortness of breath after dosing. This should be treated immediately with a different fast-acting inhaled bronchodilator. Respigen® Inhaler should be discontinued immediately and alternative therapy started if necessary.
4.9 Overdose
A cardioselective B-blocking agent is the preferred antidote in salbutamol overdose. However, B-blocking drugs need to be used with caution in patients with a history of bronchospasm.
Overdosage with salbutamol can cause hypokalaemia and therefore serum potassium levels should be monitored.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
ATC Code: R03AC02
Salbutamol is a selective B2-adrenoceptor agonist. At therapeutic doses it acts on the B2-adrenoceptors of bronchial muscle providing short-acting (4 - 6 hours) bronchodilatation with a fast onset (within 5 minutes) in reversible airways obstruction.
Special Patient Population
Children < 4 years of age
Peadiatric clinical studies conducted at the recommended dose (SB020001, SB030001, SB030002), in patients < 4 years with bronchospasm associated with reversible obstructive airways disease, show that salbutamol has a safety profile comparable to that in children > 4 years, adolescents and adults.
5.2 Pharmacokinetic properties
Salbutamol has a half-life of 4 to 6 hours when administered intravenously. It is mainly cleared renally, partly as unchanged drug and partly by metabolism to the inactive 4'-O-sulphate ester. The faeces are a minor route of excretion.
Following inhalation, between 10 and 20% of the dose reaches the lower airways.
The remainder is retained in the delivery system or is deposited in the oropharynx from where it is swallowed. The fraction deposited in the airways is absorbed through the pulmonary tissues into the circulation, but is not metabolised by the lung. Once in the systemic circulation it is available for hepatic metabolism and is excreted, primarily in the urine, as unchanged drug and as the 4'-O-sulphate ester.
The part of an inhaled dose that is swallowed is absorbed from the gastrointestinal tract and undergoes considerable first-pass metabolism to the 4'-O-sulphate ester.
The primary route of excretion of both unchanged drug and conjugate is in the urine. Whether given intravenously, orally or by inhalation the majority of the salbutamol is excreted within 72 hours. Only about 10% of salbutamol is bound to plasma proteins.
5.3 Preclinical safety data
Propellant HFA 134a
In animal studies propellant HFA 134a has been shown to have no significant pharmacological effects other than at very high exposure concentrations when narcosis and a relatively weak cardiac sensitising effect were found. The potency of the cardiac sensitisation was less than that of CFC-11 (trichlorofluoromethane).
In studies to detect toxicity repeated high dose levels of propellant HFA 134a indicated that safety margins based on systemic exposure would be in the order 2200, 1314 and 381 for mouse, rat and dog with respect to humans.
There are no reasons to consider propellant HFA 134a as a potential mutagen, clastogen or carcinogen judged from in vitro and in vivo studies including long-term administration by inhalation in rodents.
Salbutamol
In common with other potent selective p2-agonists, salbutamol has been shown to be teratogenic in mice when given subcutaneously. In a reproductive study, 9.3% of fetuses were found to have cleft palate at 2.5mg/kg, 4 times the maximum human oral dose. In rats, treatment at the levels of 0.5, 2.32, 10.75 and 50mg/kg/day orally throughout the pregnancy resulted in no significant fetal abnormalities. The only toxic effect was an increase in neonatal mortality at the highest dose level as the result of lack of maternal care. A reproductive study in rabbits revealed cranial malformations in 37% of fetuses at 50mg/kg/day, 78 times the maximum human oral dose.
Respigen® Inhaler
In a bridging inhalation toxicity study, in which dogs were exposed to Respigen® at nominal doses of up to 0.3mg/kg/day, the only notable findings were clinical signs on the cardiovascular system, consisting of tachycardia, a marked carotid pulse and reddening of the ears and gums. These signs were considered to be due to the pharmacological (beta-adrenergic) activity of the drug.
6.1 List of excipients
Oleic acid Ethanol, anhydrous HFA 134a
6.2 Incompatibilities
None known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Do not store above 30°C. Protect from frost and direct sunlight.
The canister contains a pressurised liquid. Do not expose to temperatures higher than 50°C. Do not pierce the canister.
6.5 Nature and contents of container
22 x 59 mm aluminium can sealed with a 50 microlitre metered dose valve, packed into a blue L-shaped actuator.
Each canister contains 200 actuations.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Generics [UK] Limited,
Station Close,
Potters Bar,
Hertfordshire EN6 1TL
8 MARKETING AUTHORISATION NUMBER(S)
PL 04569/0455
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/08/2010
10 DATE OF REVISION OF THE TEXT
23/11/2012