PROXOR

Posology Proxor is not intended for the initial management of asthma. The dosage of the components of Proxor 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 Proxor is characterised by an extrafine particle size distribution which results in a more potent effect than formulations of beclometasone dipropionate with a non-extra fine particle size distribution (100 micrograms of beclometasone dipropionate extrafine in Proxor are equivalent to 250 micrograms of beclometasone dipropionate in a non-extrafine formulation).

Therefore, the total daily dose of beclometasone dipropionate administered in Proxor 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 Proxor; the dose of beclometasone dipropionate should be lower and will need to be adjusted to the individual needs of the patients.

Dose recommendations for adults 18 years and above:

Two inhalations twice daily. The maximum daily dose is 4 inhalations. Proxor 200/6 should be used as maintenance therapy only. A lower strength (Proxor 100/6) is available for maintenance and reliever therapy. Patients should be advised to have their separate short-acting bronchodilator available for rescue use at all times.

Patients should be regularly reassessed by a doctor, so that the dosage of Proxor 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 long term control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid alone. Proxor 200/6 should not be used for step-down treatment but a lower strength of the beclometasone dipropionate component in the same inhaler is available for step-down treatment (Proxor 100/6 micrograms).

Patients should be advised to take Proxor every day even when asymptomatic.

Special patient groups:

There is no need to adjust the dose in elderly patients. 2).

Dose recommendations for children and adolescents under 18 years:

Proxor 200/6 should not be used in children and adolescents less than 18 years. Method of administration Proxor is for inhalation use. To ensure proper administration of the drug, the patient should be shown how to use the medicinal product 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.

Proxor inhaler is provided with a counter on the back of the actuator, which shows how many doses are left. For the 120 doses presentation each time the patient press 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 or 180.

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 should stand or sit in an upright position when inhaling from their inhaler.

1. Patients should remove the protective cap from the mouthpiece and check that the mouthpiece is clean and free from dust and dirt or any other foreign objects. 2. Patients should breathe out as slowly and deeply as possible. 3. Patients should hold the canister vertically with its body upwards and put the lips around the mouthpiece without biting the mouthpiece.

4. At the same time, patients should breathe in slowly and deeply through the mouth. After starting to breathe in, they should press down on the top of the inhaler to release one puff. 5. Patients should hold the breath for as long as possible and, finally, they should remove the inhaler from the mouth and breathe out slowly.

Patients should not breathe out into the inhaler. To inhale a further puff, patients should keep the inhaler in a vertical position for about half a minute and repeat steps 2 to 5. IMPORTANT: patients should not perform steps 2 to 5 too quickly.

After use, patients should close the inhaler with protective cap and check the dose counter. Patients should be advised to get a new inhaler when the dose counter or indicator shows the number 20. They should stop using the inhaler when the counter shows 0 as any puffs left in the device may not be enough to release a full dose.

If mist appears following inhalation, either from the inhaler or from the sides of the mouth, the procedure should be repeated from step 2. For patients with weak hands it may be easier to hold the inhaler with both hands. Therefore, the index fingers should be placed on the top […]

As Proxor contains beclometasone dipropionate and formoterol fumarate dihydrate, 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 (Proxor) 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 < 1/1,000) and very rare (≤1/10,000), 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*, Uncommon Ventricular extrasystoles, angina pectoris Rare Cardiac disorders 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 Oedema peripheral Very rare conditions 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 'Special Warnings and Precautions for Use'). Among the observed adverse reactions those typically associated with formoterol are: hypokalemia, headache, tremor, palpitations, cough, muscle spasms and prolongation of QTc interval.

Adverse reactions typically associated with the administration of beclomethasone 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 Proxor. g. 4). Hypersensitivity reactions including rash, urticaria pruritus, erythema 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 a medicinal containing beclometasone dipropionate and formoterol was not different to that of beclomethasone dipropionate monotherapy. Beclometasone/Formoterol paediatric experimental formulation of beclometasone dipropionate and formoterol fumarate 50/6 micrograms per actuation administered to asthmatic children aged 5-11 years over 12 weeks tratement period, showed a safety profile similar to the approved marketed formoterol and beclometasone dipropionate single agents.

However, the same paediatric formulation of Beclometasone/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/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Proxor 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 Proxor 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 Proxor 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, Proxor 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 Proxor 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 Proxor 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 Proxor. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Proxor.

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. Proxor should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

Proxor 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 Proxor (for patients using Proxor as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for patients using Proxor as maintenance therapy only).

Patients should be reminded to take Proxor daily as prescribed even when asymptomatic. g. 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 Proxor.

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 does not change, there is no increased risk of systemic effects when using beclometasone dipropionate/formoterol with the named spacer device.

Prolonged treatment of patients with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Children aged less than 16 years taking/inhaling higher than recommended doses of beclometasone dipropionate may […]

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