COMBIPRASAL

Posology The recommended dose is:

Adults (including elderly patients and children over 12 years) The contents of one single-dose container three or four times daily. Paediatric population (under 12 years) The safety and efficacy of COMBIPRASAL in children aged under 12 years have not been established.

COMBIPRASAL is not recommended in children below 12 years of age. Method of administration Inhalation use. 7 * Median Mass Diameter No information is available in respect of pulmonary inhalation and deposition patterns across nebuliser systems that have not been studied.

The use of an alternative untested nebuliser system may alter the pulmonary deposition of the active substances, this in turn may alter the efficacy and safety of the product and dose adjustment may then become necessary. Instructions for use with the eFlow rapid electronic nebuliser: 1.

The nebuliser should be prepared by following the manufacturer’s instructions. 2. A new single-dose container should be carefully separated from the strip. 3. The remaining single-dose containers should be put back in the sachet and the sachet should be closed by crimping over the lap.

The sachet should be stored in the carton. 4. The single-dose container should be held upright and opened by simply twisting off the top. 5. Unless otherwise indicated the contents of one single-dose container should be squeezed into the nebuliser chamber.

6. The nebuliser chamber should be closed by placing the cap on the nebuliser chamber so that the slots in the side of the cap are positioned above the notches in the chamber. Pressing gently the cap should be turned clockwise as far as it will go.

The closing mechanism is functioning correctly if the cap seal rises with the turning motion to form a seal. It should be checked that all parts are connected tightly and that the nebuliser chamber is sealed. 7. The patient should hold the nebuliser handset in his/her hand and sit in an upright position and relax.

The mouthpiece should be taken between the teeth and the lips should be closed around it. The lips should not touch the blue expiratory valve. The ON/OFF button on the control unit should be pressed. A green LED beside the ON/OFF button lights up and an audible signal (1 beep) is emitted to indicate proper functioning.

The patient should be instructed to inhale and exhale through the mouthpiece as slowly and deeply as possible. 8. The nebuliser device switches off automatically when the nebuliser solution is used up. When inhalation has been completed successfully a tick will appear on the display.

Any remaining solution (about 1 ml cannot be nebulised and remains in the nebuliser chamber) should be discarded. 9. When the inhalation session has ended the power adapter plug should be disconnected from the socket. Instructions for use with the PARI LC Sprint nebuliser: 1.

The nebuliser is operated with the PARI Boy SX compressor and should be prepared by following the manufacturer’s instructions. 2. A new single-dose container should be carefully separated from the strip. 3. The remaining single-dose containers should be put back in the sachet and the sachet should be closed by crimping over the lap.

The sachet should be stored in the carton. 4. The single-dose container should be held upright and opened by simply twisting off the top. 5. The closure on the nebuliser upper section should be released by pressing the thumb against the underside of the cap.

6. Unless otherwise indicated the contents of one single-dose container should be squeezed into the nebuliser chamber. 7. The cap of the nebuliser should be closed. The cap should snap into place. All parts of the nebuliser should be firmly connected to each other.

8. The patient should sit in an upright position and relax. The compressor should be switched on. The mouthpiece should be taken between the teeth and the lips should be closed around it. The patient should be instructed to breathe in through the mouthpiece as slowly and deeply as possible and to breathe out in their own time.

9. The inhalation should be continued until the solution in the nebuliser chamber is used up (signalled by a change in the sound of the nebuliser). 10. The compressor should be switched off as soon as inhalation is finished. Any remaining solution in the nebuliser chamber (some solution will remain after inhalation) should be discarded.

For eFlow rapid electronic nebuliser and PARI LC Sprint nebuliser:

The manufacturer’s instructions should be followed for cleaning the nebuliser. It is important that the nebuliser is kept clean. The full instructions for use of the nebuliser in the leaflet provided with the nebuliser system should be read before starting the inhalation.

As the single-dose containers contain no preservatives it is important that the contents are used immediately after opening and a fresh single-dose container is used for each administration to avoid microbial contamination. Partly used, opened or damaged single-dose containers should be discarded.

Summary of the safety profile Many of the listed undesirable effects can be assigned to the anticholinergic and beta2 sympathomimetic properties of the medicinal product. As with all inhalation therapy COMBIPRASAL may show symptoms of local irritation.

Adverse reactions were identified from data obtained in clinical trials and post- approval data of nebuliser solutions containing the combination ipratropium bromide and salbutamol. The most frequent side effects reported in clinical trials were headache, throat irritation, cough, dry mouth, gastrointestinal motility disorders (including constipation, diarrhoea and vomiting), nausea and dizziness.

Tabulated list of adverse reactions Based on the MedDRA system organ class and frequencies, adverse events are listed in the table below. Frequencies are defined as: very common (≥1/10) common (≥1/100 to <1/10) uncommon (≥1/1,000 to <1/100) rare (≥1/10,000 to <1/1,000) very rare (<1/10,000) not known (cannot be estimated from the available data) The following side effects have been reported based on clinical trials involving 3488 patients.

4. (2) as with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway.

4. (3) the risk of urinary retention may be increased in patients with pre-existing urinary outflow tract obstruction. The following other side effects have also been reported rarely for nebuliser solutions containing ipratropium bromide and salbutamol: restlessness, hyperactivity in children, anxiety, depression, extrasystoles, dyspnoea.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

If it is necessary to use higher doses than recommended to control the symptoms of bronchoconstriction (or bronchospasm) the patient’s treatment plan should be reassessed. Dyspnoea Patients should be instructed to consult a doctor immediately in the event of acute, rapidly worsening dyspnoea or if a reduced response to treatment becomes apparent.

Hypersensitivity Immediate hypersensitivity reactions may occur after administration as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, oropharyngeal oedema and anaphylaxis. Paradoxical bronchospasm As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing.

Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway. COMBIPRASAL should be discontinued immediately, the patient should be assessed and alternative therapy instituted if necessary.

Ocular complications There have been rare reports of ocular complications when aerosolised ipratropium bromide, either alone or in combination with a beta2-adrenergic agonist, has been inadvertently sprayed into the eye. Patients must therefore be instructed in the correct use of COMBIPRASAL with their nebuliser and warned not to allow the solution or mist to enter the eyes.

To avoid inadvertent entry of drug into the eye, it is preferable to administer the nebulised solution using a mouthpiece rather than a face mask. Such ocular complications may include, mydriasis, blurring of vision, increased intraocular pressure, eye pain and narrow-angle glaucoma (including acute narrow- angle glaucoma).

Patients who may be susceptible to glaucoma should be warned specifically about the need for ocular protection. Antiglaucoma therapy is effective in the prevention of acute narrow-angle glaucoma in susceptible individuals. Eye pain or discomfort, blurred vision, visual halos or coloured images, in association with red eyes from conjunctival congestion or corneal oedema may be signs of acute narrow-angle glaucoma.

Should any combination of these symptoms develops, treatment with miotic eye drops should be initiated and the patient should seek specialist advice immediately. Systemic effects In the following conditions COMBIPRASAL should only be used after careful risk/benefit assessment: inadequately controlled diabetes mellitus, recent myocardial infarction and/or severe organic heart or vascular disorders, hyperthyroidism, pheochromocytoma, prostatic hypertrophy, bladder-neck obstruction and risk of narrow-angle glaucoma.

Cardiovascular effects Cardiovascular effects may be seen with sympathomimetic drugs, including medicinal products containing salbutamol. There is some evidence from post- marketing data and published literature of rare occurrences of myocardial ischaemia associated with salbutamol.

g. ischaemic heart disease, arrhythmias or severe heart failure) who are receiving salbutamol for respiratory disease 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 either respiratory or cardiac in origin. Hypokalaemia Potentially serious hypokalaemia may result from beta2-agonist therapy. Particular caution is advised in severe airway obstruction, as this effect may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics.

Hypokalaemia can bring about increased sensitivity to arrhythmias in patients being treated with digoxin. Additionally, hypoxia may aggravate the effects of hypokalaemia on cardiac rhythm. It is recommended that serum levels of potassium are monitored in such situations.

Gastro-intestinal motility disturbances Patients with cystic fibrosis may be more prone to gastro-intestinal motility disturbances and therefore ipratropium bromide, as with other anticholinergics, should be used with caution in these patients.

9). Increase in lactate levels may lead to dyspnoea and compensatory hyperventilation, which could be misinterpreted as a sign of asthma treatment failure and lead to inappropriate intensification of short- acting beta-agonist treatment.

It is therefore recommended that patients are monitored for the development of elevated serum lactate and consequent metabolic acidosis in this setting. Interference with laboratory tests or other diagnostic measures The use of COMBIPRASAL may lead to positive results in doping tests.

2). Dental caries Dental caries has been reported with salbutamol use. It is recommended, particularly in children, to pay attention to proper oral hygiene and perform regular dental checkups.

Patients with hypertrophic obstructive cardiomyopathy or tachyarrhythmia. 1.