FOSTER NEXTHALER Inhalation powder Ref.[115941] Active ingredients: Beclometasone Eformoterol

It is recommended that the dose is tapered when the treatment is discontinued; treatment should not be stopped abruptly.

The management of asthma should normally follow a stepwise programme and patient response should be monitored clinically and by lung function tests.

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

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

FOSTER NEXThaler is not intended for the initial management of asthma.

For treatment of acute asthma attacks patients should be advised to have their short-acting bronchodilator available at all times, either Foster NEXThaler (for patients using Foster NEXThaler as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for patients using Foster NEXThaler as maintenance therapy only).

Patients should be reminded to take Foster NEXThaler daily as prescribed even when asymptomatic. The reliever inhalations of Foster NEXThaler should be taken in response to asthma symptoms, but are not intended for regular prophylactic use, e.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 Foster NEXThaler. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Foster NEXThaler should be used (see section 4.2).

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 effects of inhaled corticosteroids may occur, particularly at high doses prescribed for prolonged periods. 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 in children and adolescents, decrease in bone mineral density, cataract, glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is important therefore that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control of asthma is maintained.

Prolonged treatment of patients with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Children and adolescents aged less than 16 years inhaling higher than recommended doses of beclometasone dipropionate may be at particular risk. Situations which could potentially trigger acute adrenal crisis, include trauma, surgery, infection or any rapid reduction in dosage. Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, hypotension, decreased level of consciousness, hypoglycaemia, and seizures. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery.

Patients transferring from oral to inhaled corticosteroids may remain at risk of impaired adrenal reserve for a considerable time. Patients who have required high dose emergency corticosteroid therapy in the past or have received prolonged treatment with high doses of inhaled corticosteroids may also be at risk. This possibility of residual impairment should always be borne in mind in emergency and elective situations likely to produce stress, and appropriate corticosteroid treatment must be considered. The extent of the adrenal impairment may require specialist advice before elective procedures.

Foster NEXThaler should be administered with caution in patients with active or quiescent pulmonary tuberculosis, fungal and viral infections in the airways.

Foster NEXThaler should be used with caution (which may include monitoring) in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias, idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, ischaemic heart disease, severe heart failure, severe arterial hypertension and aneurysm.

Caution should also be observed when treating patients with known or suspected prolongation of the QTc interval, either congenital or drug induced (QTc >0.44 seconds). Formoterol itself may induce prolongation of the QTc interval.

Caution is also required when Foster NEXThaler 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. Hypokalaemia may also be potentiated by concomitant treatment with other drugs which can induce hypokalaemia, such as xanthine derivatives, steroids and diuretics (see section 4.5). 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 Foster NEXThaler is not administered for at least 12 hours before the start of anaesthesia as there is a risk of cardiac arrhythmias.

Patients should be advised to rinse the mouth or gargle with water or brush the teeth after inhaling the prescribed dose to minimise the risk of oropharyngeal fungal infections and dysphonia. This medicinal product contains lactose. Lactose contains small amounts of milk proteins, which may cause allergic reactions. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Visual disturbances

Visual disturbances may be reported with systemic and topical corticosteroids 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 disease such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Pharmacokinetic interactions

Beclometasone dipropionate undergoes a very rapid metabolism via esterase enzymes without involvement of cytochrome P450 system.

Beclomethasone is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions are unlikely; however the possibility of systemic effects with concomitant use of strong CYP3a inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and appropriate monitoring is advised with the use of such agents.

Pharmacodynamic interactions

Beta-blockers (including eye drops) should be avoided in asthmatic patients. If beta-blockers are administered for compelling reasons, the effect of formoterol will be reduced or abolished.

The use of other beta-adrenergic drugs may have potentially additive effects, therefore caution is required when theophylline or other beta-adrenerigic drugs are prescribed concomitantly with formoterol.

Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, certain antihistamines (e.g. terfenadine), monoamine oxidase inhibitors and tricyclic antidepressants can prolong the QTc-interval and increase the risk of ventricular arrhythmias.

In addition L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta₂-sympathomimetics.

Concomitant treatment with monoamine oxidase inhibitors including agents with similar properties such as furazolidone and procarbazine may precipitate hypertensive reactions.

There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.

Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate a possible hypokalaemic effect of beta2-agonists (see section 4.4). Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.

Fertility

There are no data in humans. In animal studies in rats, the presence of beclometasone dipropionate at high doses in the combination was associated with reduced female fertility and embryotoxicity (see section 5.3).

Pregnancy

There are no relevant clinical data on the use of Foster NEXThaler in pregnant women. Animal studies using beclometasone dipropionate and formoterol combination showed evidence of toxicity to reproduction and to the fetuses after high systemic exposure (see section 5.3). High doses of corticosteroids administered to pregnant animals are known to cause abnormalities of fetal development including cleft palate and intra-uterine growth retardation. Because of the tocolytic actions of beta₂-sympathomimetic agents particular care should be exercised in the run up to delivery. Formoterol should not be recommended for use during pregnancy and particularly at the end of pregnancy or during labour unless there is no other (safer) established alternative.

Administration of Foster NEXThaler during pregnancy should only be considered if the expected benefits outweigh the potential risks.

Lactation

There are no relevant clinical data on the use of Foster NEXThaler during lactation in humans. Although no data from animal experiments are available, it is reasonable to assume that beclometasone dipropionate is secreted in milk, like other corticosteroids.

While it is not known whether formoterol passes into human breast milk, it has been detected in the milk of lactating animals.

Administration of Foster NEXThaler to women who are breast-feeding should be considered if the expected benefits outweigh the potential risks. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Foster NEXThaler therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Foster NEXThaler has no or negligible influence on the ability to drive and use machines.

The most common adverse reaction is tremor. In a 12-week clinical trial with Foster NEXThaler, tremor was seen only with the highest dose regimen (2 inhalations bid), appeared most frequently at the beginning of treatment and was mild in intensity. No patient was withdrawn from the trial as a result of tremor.

Clinical Trials Experience in asthma patients

The safety of Foster NEXThaler was assessed in active- and placebo-controlled clinical trials in which 719 patients aged 12 and older with asthma of varying severity were exposed to the drug. The incidence of adverse reactions in the table below relates to asthmatic patients aged 12 years and older and is based upon the safety findings of two pivotal clinical trials where Foster NEXThaler was administered at the doses recommended in this package insert for a period of 8-12 weeks. No psychiatric disorders were observed in the clinical trials with Foster NEXThaler but they are included in the table as a potential class-effect of inhaled corticosteroids.

Undesirable effects which have been associated with beclometasone dipropionate and formoterol administered as a fixed combination (Foster NEXThaler) 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) and very rare (<1/10,000), not known (cannot be estimated from the available data).

Among the observed adverse reactions those typically associated with formoterol are: tremor, headache, tachycardia, sinus bradycardia, angina pectoris, myocardial ischaemia, QT prolongation.

Among the observed adverse reactions those typically associated with beclometasone dipropionate are: nasopharyngitis, oral candidiasis, dysphonia, throat irritation, irritability, cortisol free urine decreased, blood cortisol decreased, blood glucose increased.

Additional adverse reactions not observed in the clinical experience with Foster NEXThaler but typically associated with the inhaled administration of beclometasone dipropionate are other oral fungal infections. Taste disturbances have occasionally been reported during inhaled corticosteroid therapy.

See section 4.4 for measures to minimize the occurrence of oral fungal infections, oral candidiasis and dysphonia.

Systemic effects of inhaled corticosteroids (e.g. beclometasone dipropionate) may occur particularly when administered at high doses prescribed for prolonged periods, these may include Cushing's Syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma (see also section 4.4).

Additional adverse reactions not observed in the clinical experience with therapeutic doses of Foster NEXThaler but typically associated with the administration of beta₂-agonist such as formoterol are palpitations, atrial fibrillation, ventricular extrasystoles, tachyarrhythmia, potentially serious hypokalaemia and increase/decrease of blood pressure. Insomnia, dizziness, restlessness, and anxiety have occasionally been reported during inhaled formoterol therapy. Formoterol may also induce muscle cramps, myalgia.

Hypersensitivity reactions including rashes, urticaria, pruritus and erythema and oedema of the eye, face, lips and throat (angioedema) have been reported.

As with other inhalation therapy paradoxical bronchospasm may occur with an immediate increase in wheezing, cough and shortness of breath after dosing (see also section 4.4).

Paediatric population

There is no information on the safety of Foster NEXThaler in children up to 11 years of age, and only limited information in adolescents 12–17 years of age. In a 12 weeks randomised clinical trial in adults and adolescents, 162 adolescents aged 12–17 years with moderate to severe asthma received Foster NEXThaler or the corresponding pressurised inhalation solution formulation, 1 or 2 inhalations bid; the frequency, type and severity of adverse drug reactions were not different in adolescents compared to adults.

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. Healthcare professionals are asked to report any suspected adverse reactions.

Not applicable.