Innovair should be used with caution (which may include monitoring) in patients with cardiac arrhythmias, especially 3rd 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 sec). Formoterol itself may induce prolongation of the QTc interval.
Caution is also required when Innovair is used by patients with thyrotoxicosis, diabetes mellitus, phaeochromocytoma and untreated hypokalaemia.
Potentially serious hypokalaemia may result from β2-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, eg, 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 Innovair is not administered for at least 12 hrs before the start of anaesthesia as there is a risk of cardiac arrhythmias.
As with all inhaled medication containing corticosteroids, Innovair 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 Innovair 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 re-assessment 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 increase treatment with corticosteroids, either inhaled or oral therapy, or antibiotic treatment if an infection is suspected.
Patients should not be initiated on Innovair 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 Innovair. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Innovair.
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. Innovair should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
Innovair should not be used as the 1st treatment for asthma.
For treatment of acute asthma attacks, patients should be advised to have their short-acting bronchodilator available at all times. Patients should be reminded to take Innovair daily as prescribed even when asymptomatic.
Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Innovair. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Innovair 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.
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.
Single dose pharmacokinetic data have demonstrated that the use of Innovair with 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 Innovair 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 <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 Innovair 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.
Patients should be advised that Innovair contains a small amount of ethanol (approximately 7 mg/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.
Effects on the Ability to Drive or Operate Machinery: Innovair is unlikely to have any effect on the ability to drive and operate machinery.
Use in pregnancy & lactation: 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 Innovair in pregnant women. Animal studies using beclometasone dipropionate and formoterol combination showed evidence of toxicity to reproduction after high systemic exposure (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
Because of the tocolytic actions of β2-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.
Innovair 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 Innovair 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 Innovair to women who are breastfeeding should only be considered if the expected benefits outweigh the potential risks.
Use in children: There is no experience with Innovair in children <12 years of age. Only limited data are available in adolescents between 12 and 18 years of age. Therefore, Innovair is not recommended for children and adolescents <18 years until further data become available.