BIBECFO

Posology Asthma This medicinal product is not intended for the initial management of asthma. The dosage of the components of this medicinal product is individual and should be adjusted to the severity of the disease. This should be considered not only when treatment with combination products is initiated but also when the dose is adjusted.

If an individual patient should require a combination of doses other than those available in the combination inhaler, appropriate doses of beta2-agonists and/or corticosteroids by individual inhalers should be prescribed. Beclometasone dipropionate in this medicinal product is characterised by an extrafine particle size distribution which results in a more potent effect than formulations of beclometasone dipropionate with a non-extrafine particle size distribution (100 micrograms of beclometasone dipropionate extrafine in this medicinal product are equivalent to 250 micrograms of beclometasone dipropionate in a non-extrafine formulation).

Therefore, the total daily dose of beclometasone dipropionate administered in this medicinal product should be lower than the total daily dose of beclometasone dipropionate administered in a non-extrafine beclometasone dipropionate formulation.

This should be taken into consideration when a patient is transferred from a beclometasone dipropionate non-extrafine formulation to this medicinal product; the dose of beclometasone dipropionate should be lower and will need to be adjusted to the individual needs of the patients.

There are two treatment approaches:

A.

Maintenance therapy:

This medicinal product is taken as regular maintenance treatment with a separate as needed rapid-acting bronchodilator. B.

Maintenance and reliever therapy:

This medicinal product is taken as regular maintenance treatment and as needed in response to asthma symptoms. A. Maintenance therapy Patients should be advised to have their separate rapid-acting bronchodilator available for rescue use at all times.

Dose recommendations for adults 18 years and above:

One or two inhalations twice daily. The maximum daily dose is 4 inhalations. B. Maintenance and reliever therapy Patients take their daily maintenance dose of this medicinal product and in addition take this medicinal product as needed in response to asthma symptoms.

Patients should be advised to always have this medicinal product available for rescue use. This medicinal product maintenance and reliever therapy should especially be considered for patients with: • not fully controlled asthma and in need of reliever medication • asthma exacerbations in the past requiring medical intervention Close monitoring for dose-related adverse effects is needed in patients who frequently take high numbers of this medicinal product as-needed inhalations.

Dose recommendations for adults 18 years and above:

The recommended maintenance dose is 1 inhalation twice daily (one inhalation in the morning and one inhalation in the evening). Patients should take 1 additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken.

The maximum daily dose is 8 inhalations. Patients requiring frequent use of rescue inhalations daily should be strongly recommended to seek medical advice. Their asthma should be reassessed and their maintenance therapy should be reconsidered.

Dose recommendations for children and adolescents under 18 years:

The safety and efficacy of beclometasone dipropionate/formoterol in children and adolescents under 18 years of age have not been established. 2, but no recommendation on a posology can be made. Patients should be regularly reassessed by a doctor, so that the dosage of this medicinal product remains optimal and is only changed on medical advice.

The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. When control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid alone.

Patients should be advised to take this medicinal product every day even when asymptomatic.

COPD Dose recommendations for adults 18 years and above:

Two inhalations twice daily. Special patient groups There is no need to adjust the dose in elderly patients. 2). Method of administration This medicinal product is for inhalation use. To ensure proper administration of the drug, the patient should be shown how to use the inhaler correctly by a physician or other health professional.

Correct use of the pressurised metered dose inhaler is essential in order that treatment is successful. The patient should be advised to read the Patient Information Leaflet carefully and follow the instructions for use as given in the Leaflet.

This medicinal product inhaler is provided with a counter on the back of the actuator, which shows how many doses are left. This medicinal product inhaler 120 doses presentation each time the patient presses the canister, a puff of medicine is released, and the counter counts down by one.

Patients should be advised not to drop the inhaler as this may cause the counter to count down. Testing the inhaler Before using the inhaler for the first time or if the inhaler has not been used for 14 days or more, the patient should release one actuation into the air in order to ensure that the inhaler is working properly.

After testing the inhaler for the first time, the counter should read 120. Use of the inhaler If the inhaler has been exposed to severe cold, patients should warm it with their hands for a few minutes before using it. They should never warm it by artificial means.

Whenever possible patients […]

As this medicinal product contains beclometasone dipropionate and formoterol, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the two compounds.

Undesirable effects which have been associated with beclometasone dipropionate and formoterol administered as a fixed combination (beclometasone dipropionate/formoterol) and as single agents are given below, listed by system organ class.

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) and not known (cannot be estimated from the available data). Common and uncommon ADRs were derived from clinical trials in asthmatic and COPD patients.

4) Not known Ear and labyrinth disorders Otosalpingitis Uncommon Palpitations, electrocardiogram QT corrected interval prolonged, electrocardiogram change, tachycardia, tachyarrhythmia, atrial fibrillation* UncommonCardiac disorders Ventricular extrasystoles, angina pectoris Rare Vascular disorders Hyperaemia, flushing Uncommon Dysphonia Common Cough, productive cough, throat irritation, asthmatic crisis Uncommon Bronchospasm paradoxical Rare Respiratory, thoracic and mediastinal disorders Dyspnoea, exacerbation of asthma Very rare Gastrointestinal disorders Diarrhoea, dry mouth, dyspepsia, dysphagia, burning sensation of the lips, nausea, dysgeusia Uncommon Pruritus, rash, hyperhidrosis, urticaria UncommonSkin and subcutaneous tissue disorders Angioedema Rare Muscle spasms, myalgia UncommonMusculoskeletal and connective tissue disorders Growth retardation in children and adolescents Very rare Renal and urinary disorders Nephritis Rare General disorders and administration site conditions Oedema peripheral Very rare C-reactive protein increased, platelet count increased, free fatty acids increased, blood insulin increased, blood ketone body increased, blood cortisol decrease* Uncommon Blood pressure increased, blood pressure decreased Rare Investigations Bone density decreased Very rare * One related non serious case of pneumonia was reported by one patient treated with beclometasone dipropionate/formoterol in a pivotal clinical trial in COPD patients.

Other adverse reactions observed with beclometasone dipropionate/formoterol in COPD clinical trials were reduction of blood cortisol and atrial fibrillation. 4). Among the observed adverse reactions those typically associated with formoterol are: hypokalaemia, headache, tremor, palpitations, cough, muscle spasms and prolongation of QTc interval.

Adverse reactions typically associated with the administration of beclometasone dipropionate are: oral fungal infections, oral candidiasis, dysphonia, throat irritation. Dysphonia and candidiasis may be relieved by gargling or rinsing the mouth with water or brushing the teeth after using the product.

Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst continuing the treatment with beclometasone dipropionate/formoterol. 4). Hypersensitivity reactions including rash, urticaria pruritus, erhythema and oedema of the eyes, face, lips and throat may also occur.

Paediatric population In a 12-week study in adolescent asthma patients, the safety profile of beclometasone dipropionate/formoterol was not different to that of beclometasone dipropionate monotherapy. Beclometasone dipropionate/Formoterol paediatric experimental formulation of beclometasone dipropionate and formoterol 50/6 micrograms per actuation administered to asthmatic children aged 5-11 years over 12 weeks treatment period, showed a safety profile similar to the approved marketed formoterol and beclometasone dipropionate single agents.

However, the same paediatric formulation of beclometasone dipropionate/formoterol 50/6 micrograms administered to asthmatic children aged 5-11 years over 2 weeks did not demonstrate non-inferiority to the free combination of marketed formoterol and beclometasone dipropionate single agents in terms of lower leg growth rate.

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/ or search for MHRA Yellow Card in the Google Play or Apple App Store.

Beclometasone dipropionate/Formoterol should be used with caution (which may include monitoring) in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heart beat), idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease, particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure, occlusive vascular diseases, particularly arteriosclerosis, arterial hypertension and aneurysm.

44 seconds). Formoterol itself may induce prolongation of the QTc interval. Caution is also required when this medicinal product is used by patients with thyrotoxicosis, diabetes mellitus, phaeochromocytoma and untreated hypokalaemia.

Potentially serious hypokalaemia may result from beta2-agonist therapy. Particular caution is advised in severe asthma as this effect may be potentiated by hypoxia. 5). Caution is also recommended in unstable asthma when a number of “rescue” bronchodilators may be used.

It is recommended that serum potassium levels are monitored in such situations. The inhalation of formoterol may cause a rise in blood glucose levels. Therefore, blood glucose should be closely monitored in patients with diabetes. If anaesthesia with halogenated anaesthetics is planned, it should be ensured that this medicinal product is not administered for at least 12 hours before the start of anaesthesia as there is a risk of cardiac arrhythmias.

As with all inhaled medication containing corticosteroids, this medicinal product should be administered with caution in patients with active or quiescent pulmonary tuberculosis, fungal and viral infections in the airways. It is recommended that treatment with this medicinal product should not be stopped abruptly.

If patients find the treatment ineffective medical attention must be sought. Increasing use of rescue bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the asthma therapy. Sudden and progressive deterioration in control of asthma or COPD is potentially life- threatening and the patient should undergo urgent medical assessment.

Consideration should be given to the need for increased treatment with corticosteroids, either inhaled or oral therapy, or antibiotic treatment if an infection is suspected. Patients should not be initiated on beclometasone dipropionate/formoterol during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma.

Serious asthma-related adverse events and exacerbations may occur during treatment with beclometasone dipropionate/formoterol. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on this medicinal product.

As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing and rapidness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator. This medicinal product should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

This medicinal product should not be used as the first treatment for asthma. For treatment of acute asthma attacks patients should be advised to have their rapid-acting bronchodilator available at all times, either beclometasone dipropionate/formoterol (for patients using beclometasone dipropionate/formoterol as maintenance and reliever therapy) or a separate rapid- acting bronchodilator (for patients using beclometasone dipropionate/formoterol as maintenance therapy only).

Patients should be reminded to take beclometasone dipropionate/formoterol daily as prescribed even when asymptomatic. , before exercise. For such use, a separate rapid-acting bronchodilator should be considered. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of beclometasone dipropionate/formoterol.

Regular review of patients as treatment is stepped down is important. 2). Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur with inhaled than with oral corticosteroids.

Possible systemic effects include:

Cushing's syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

Therefore, it is important that the patient is reviewed regularly, and the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained. 2) have demonstrated that the use of beclometasone dipropionate/formoterol with Aerochamber Plus® spacer device in comparison to the use of standard actuator, does not increase the total systemic exposure to formoterol and reduces the systemic exposure to beclometasone-17- monopropionate, while there is an increase for unchanged beclometasone dipropionate that reaches systemic circulation from the lung; however, since the total systemic exposure to beclometasone dipropionate plus its active metabolite […]

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