Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Not for acute use
This medicinal product is not indicated for the treatment of acute episodes of bronchospasm, or to treat an acute disease exacerbation (i.e. as a rescue therapy).

Hypersensitivity

Immediate hypersensitivity reactions have been reported after administration. If signs suggesting allergic reactions occur, in particular, angioedema (including difficulties in breathing or swallowing, swelling of the tongue, lips and face), urticaria or skin rash, treatment should be discontinued immediately and alternative therapy instituted.

Paradoxical bronchospasm

Paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator (reliever). Treatment should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

Deterioration of disease

It is recommended that treatment should not be stopped abruptly. If patients find the treatment ineffective, they should continue treatment but medical attention must be sought. Increasing use of reliever bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Sudden or progressive deterioration in symptoms is potentially life-threatening and the patient should undergo urgent medical assessment.

Cardiovascular effects

Due to the presence of a long-acting beta2-agonist and a long-acting muscarinic antagonist, Trimbow 100/6/12.5 should be used with caution in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heartbeat, including atrial fibrillation), 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.
Caution should also be exercised when treating patients with known or suspected prolongation of the QTc interval (QTc > 450 milliseconds for males, or > 470 milliseconds for females), either congenital or induced by medicinal products. Patients diagnosed with the described cardiovascular conditions were excluded from clinical studies with Trimbow. Limited data in asthmatic patients with cardiovascular co-morbidities or risk- factors suggest that these patients are also at higher risk of adverse reactions like local fungal infections or dysphonia (see section 4.8).
If anaesthesia with halogenated anaesthetics is planned, it should be ensured that Trimbow 100/6/12.5 is not administered for at least 12 hours before the start of anaesthesia as there is a risk of cardiac arrhythmias.

Caution is also required when treating patients with thyrotoxicosis, diabetes mellitus, pheochromocytoma and untreated hypokalaemia.

Pneumonia in patients with COPD

An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies.

There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid products.

Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.

Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index (BMI) and severe COPD.

Systemic corticosteroid effects

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. The daily dose of Trimbow 100/6/12.5 corresponds to a medium dose of inhaled corticosteroid; furthermore, these effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include: Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation, decrease in bone mineral density 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 (see section 4.2).

Trimbow 100/6/12.5 should be administered with caution in patients with active or quiescent pulmonary tuberculosis and in patients with fungal and viral infections in the airways.

Hypokalaemia

Potentially serious hypokalaemia may result from beta2-agonist therapy. This has the potential to produce adverse cardiovascular effects. Particular caution is advised in patients with severe disease as this effect may be potentiated by hypoxia. Hypokalaemia may also be potentiated by concomitant treatment with other medicinal products which can induce hypokalaemia, such as xanthine derivatives, steroids and diuretics (see section 4.5).
Caution is also recommended when a number of reliever bronchodilators are used. It is recommended that serum potassium levels are monitored in such situations.

Hyperglycaemia

The inhalation of formoterol may cause a rise in blood glucose levels. Therefore, blood glucose should be monitored during treatment following established guidelines in patients with diabetes.

Anticholinergic effect

Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or urinary retention. Patients should be informed about the signs and symptoms of acute narrow-angle glaucoma and should be informed to stop treatment and to contact their doctor immediately should any of these signs or symptoms develop.
Additionally, due to the anticholinergic effect of glycopyrronium, the long-term co-administration with other anticholinergic-containing medicinal products is not recommended (see section 4.5).

Patients with severe renal impairment

In patients with severe renal impairment, including those with end-stage renal disease requiring dialysis, especially if associated with a significant body weight reduction, Trimbow 100/6/12.5 should be used only if the expected benefit outweighs the potential risk (see section 5.2). These patients should be monitored for potential adverse reactions.

Patients with severe hepatic impairment

In patients with severe hepatic impairment, Trimbow 100/6/12.5 should be used only if the expected benefit outweighs the potential risk (see section 5.2). These patients should be monitored for potential adverse reactions.

Prevention of oropharyngeal infections

In order to reduce the risk of oropharyngeal candida infection, patients should be advised to rinse their mouth or gargle with water without swallowing it or brush their teeth after inhaling the prescribed dose.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Stepping-down treatment

Patients should be regularly reassessed by a doctor, so that their doses of beclometasone/formoterol/glycopyrronium remain optimal and are only changed on medical advice. The doses should be titrated to the lowest doses at which effective control of asthma symptoms is maintained.

Ethanol contents

This medicinal product contains 8.856 mg of ethanol per actuation, which is equivalent to 17.712 mg per dose of two actuations. There is a theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole.

Effects on Driving

4.7    Effects on ability to drive and use machines

Trimbow 100/6/12.5 has no or negligible influence on the ability to drive and use machines.