FOSTER Pressurised inhalation solution Ref.[115942] Active ingredients: Beclometasone Eformoterol

Foster 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.

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 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. 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 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, FOSTER 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 FOSTER 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 COPDis potentially life threatening and the patient should undergo urgent medical assessment. Consideration should be given to the need for increase treatment with corticosteroids, either inhaled or oral therapy, or antibiotic treatment if an infection is suspected.

Patients should not be initiated on Foster 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. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Foster.

As with other inhalation therapy 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. Foster should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

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

Patients should be reminded to take Foster daily as prescribed even when asymptomatic. The reliever inhalations of Foster 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. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Foster should be used.

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, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioral effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).Therefore, it is important that the patient is reviewed regularly, andthe dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained.

Single dose pharmacokinetic data (see section 5.2) have demonstrated that the use of Foster 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 Foster 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 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. Care should be taken when transferring patients to Foster therapy, particularly if there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy.

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 or 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.

Psychiatric side effects can occur with the use of inhaled steroids. These include affective disorders, psychotic reactions, behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction. These symptoms typically emerge after a few days or weeks after the start of treatment.

Patients should be advised that Foster contains a small amount of ethanol (approximately 7 mg per actuation); however at normal doses the amount of ethanol is negligible and does not pose a risk to patients.

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 candida infection.

Pharmacokinetic interactions

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

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.

On the other hand, concomitant use of other beta-adrenergic drugs can 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, antihistamines, 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. Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.

Foster contains a small amount of ethanol. There is a theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole

There is no experience with or evidence of safety of propellant HFA-134a in human pregnancy or lactation. However studies of the effect of HFA-134a on reproductive function and embryofetal development in animals have revealed no clinically relevant adverse effects.

Pregnancy

There are no relevant clinical data on the use of Foster in pregnant women. Animal studies using beclometasone dipropionate and formoterol combination showed evidence of toxicity to reproduction after high systemic exposure (see 5.3 Preclinical safety data). 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. Foster should only be used during pregnancy if the expected benefits outweigh the potential risks.

Lactation

There are no relevant clinical data on the use of Foster in 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 to women who are breast-feeding should only be considered if the expected benefits outweigh the potential risks.

Foster is unlikely to have any effect on the ability to drive and operate machinery.

As Foster 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 (Foster) and as single agents are given below, listed by system organ class. Frequencies are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 <1/1,000) and very rare (≤1/10,000). Common and uncommon ADRs were derived from clinical trials in asthmatic and COPD patients.

^* One related non serious case of pneumonia was reported by one patient treated with FOSTER in a pivotal clinical trial in COPD patients. Other adverse reactions observed with FOSTER in COPD clinical trials were: reduction of blood cortisol and atrial fibrillation.

As with other inhalation therapy, paradoxical bronchospasm may occur (see 'Special Warnings and Precautions for Use').

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 Foster.

Systemic effects of inhaled corticosteroids (e.g. beclometasone dipropionate) may occur particularly when administered at high doses prescribed for prolonged periods, these may include adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma (see 'Special Warnings and Precautions for Use').

Hypersensitivity reactions including rash, urticaria pruritus, erhythema and oedema of the eyes, face, lips and throat may also occur.