OXIS Inhalation powder Ref.[27705] Active ingredients: Eformoterol

General

Oxis Turbohaler should not be used (and is not sufficient) as the first treatment for asthma.

Asthmatic patients who require therapy with long acting β₂-agonists, should also receive optimal maintenance anti-inflammatory therapy with corticosteroids. Patients must be advised to continue taking their anti-inflammatory therapy after the introduction of Oxis Turbohaler even when symptoms decrease. Should symptoms persist, or treatment with β₂-agonists need to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the maintenance therapy.

Although Oxis Turbohaler may be introduced as add-on therapy when inhaled corticosteroids do not provide adequate control of asthma symptoms, patients should not be initiated on Oxis Turbohaler during an acute severe asthma exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with Oxis Turbohaler. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Oxis Turbohaler. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Oxis Turbohaler. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Oxis Turbohaler should be used.

The maximum daily dose should not be exceeded. The long-term safety of regular treatment at higher doses than 36 micrograms per day in adults with asthma, 18 micrograms per day in children with asthma and 18 micrograms per day in patients with COPD, has not been established.

Frequent need of medication (i.e. prophylactic treatment e.g. corticosteroids and long-acting β₂-agonists)for the prevention of exercise-induced bronchoconstriction several times every week, despite an adequate maintenance treatment, can be a sign of suboptimal asthma control, and warrants a reassessment of the asthma therapy and an evaluation of the compliance.

Cardiovascular and endocrine disorders

Caution should be observed when treating patients with thyrotoxicosis, phaeochromocytoma, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.

QTc prolongation

Formoterol may induce prolongation of the QTc-interval. Caution should be observed when treating patients with prolongation of the QTc-interval and in patients treated with drugs affecting the QTc-interval (see section 4.5).

Diabetic patients

Due to the hyperglycaemic effects of β₂-agonists, additional blood glucose monitoring is recommended initially in diabetic patients.

Hypokalaemia

Potentially serious hypokalaemia may result from β₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatment with xanthine-derivatives, steroids and diuretics. The serum potassium levels should therefore be monitored.

Bronchospasm

As with other inhalation therapy, the potential for paradoxical bronchospasm should be considered. If it occurs, the treatment should be discontinued immediately and alternative therapy started (see section 4.8).

Lactose intolerance

Oxis Turbohaler contains lactose monohydrate 891 micrograms per delivered dose. This amount does not normally cause problems in lactose intolerant people. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

Children up to the age of 6 years should not be treated with Oxis Turbohaler, as no sufficient experience is available for this group.

No specific interaction studies have been carried out with Oxis Turbohaler.

Concomitant treatment with other sympathomimetic substances such as other β2-agonists or ephedrine may potentiate the undesirable effects of Oxis Turbohaler and may require titration of the dose.

Concomitant treatment with xanthine derivatives, steroids or diuretics such as thiazides and loop diuretics may potentiate a rare hypokalaemic adverse effect of β2-agonists. Hypokalaemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.

There is a theoretical risk that concomitant treatment with other drugs known to prolong the QTc-interval may give rise to a pharmacodynamic interaction with formoterol and increase the possible risk of ventricular arrhythmias. Examples of such drugs include certain antihistamines (e.g. terfenadine, astemizole, mizolastine), certain antiarrhythmics (e.g. quinidine, disopyramide, procainamide), erythromycin and tricyclic antidepressants.

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

The bronchodilating effects of formoterol can be enhanced by anticholinergic drugs.

Beta-adrenergic blockers can weaken or inhibit the effect of Oxis Turbohaler. Oxis Turbohaler should therefore not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons.

Pregnancy

There are no adequate data from the use of formoterol in pregnant women. In animal studies formoterol has caused implantation losses as well as decreased early postnatal survival and birth weight. The effects appeared at considerably higher systemic exposures than those reached during clinical use of Oxis Turbohaler. Treatment with Oxis Turbohaler may be considered at all stages of pregnancy if needed to obtain asthma control and if the expected benefit to the mother is greater than any possible risk to the foetus. The potential risk for humans is unknown.

Breast-feeding

It is not known whether formoterol passes into human breast milk. In rats, small amounts of formoterol have been detected in maternal milk. Administration of Oxis Turbohaler to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Fertility

Animal reproduction studies with formoterol have shown a somewhat reduced fertility in male rats at considerably higher systemic exposures than those reached during clinical use. Thus, these animal experimental results do not seem to be relevant in humans.

Oxis Turbohaler has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse events of β₂-agonist therapy, such as tremor and palpitations, tend to be mild and disappear within a few days of treatment.

Tabulated list of adverse reactions

Adverse reactions, which have been associated with formoterol are given below, listed by system organ class and frequency. Frequency are defined as: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1 000 and <1/100), rare (≥1/10 000 and <1/1000) and very rare <1/10 000).

^* Headache occurred in 6.5% of patients in OXIS and 6.2% on placebo.

Description of selected adverse reactions

As with all inhalation therapy, paradoxical bronchospasm may occur in very rare cases (see section 4.4).

Treatment with β₂-agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

The excipient lactose contains small amounts of milk proteins. These may cause allergic reactions.

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 via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.