ATIMOS MODULITE Pressurised inhalation solution Ref.[6862] Active ingredients: Eformoterol

Atimos Modulite 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 formoterol 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 Atimos may be introduced as add-on therapy when inhaled corticosteroids do not provide adequate control of asthma symptoms, patients should not be initiated on Atimos 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 Atimos. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Atimos.

Atimos Modulite should be used strictly in accordance with the dosage recommendations (see section 4.2). Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Atimos Modulite. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Atimos Modulite should be used.

The maximum daily dose should not be exceeded.

A sudden and progressive deterioration of the asthmatic disorder can be life-threatening and requires immediate medical intervention. Considerably exceeding the prescribed individual doses or the total daily dose can be hazardous due to the effects on the heart (cardiac arrhythmia, rise in blood pressure), in combination with changes in the salt concentrations in body fluids (electrolyte shifts), and must therefore be avoided.

Concomitant conditions

Caution should be observed when treating patients with third degree atrioventricular block, refractory diabetes mellitus, 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 and occlusive vascular diseases, especially arteriosclerosis.

Formoterol may induce prolongation of the QTc-interval. Caution should be observed when treating patients with prolongation of the QTc-interval, e.g. congenital or drug-induced (QTc >0.44 seconds) and in patients treated with drugs affecting the QTc-interval (see section 4.5).

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

If anaesthesia with halogenated anaesthetics is planned, it should be ensured that Atimos Modulite is not administered for at least 12 hours before the start of anaesthesia.

Paradoxical bronchospasm

As with every 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).

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.

Therefore potassium levels have to be regularly monitored particularly in patients with low basic potassium values or peculiar risks for decreased blood potassium levels. The monitoring should also be conducted if no decreased levels occurred under previous treatment with short acting β₂-sympathomimetics. Where applicable, potassium has to be substituted.

Due to decreased serum potassium levels the effect of digitalis containing medicinal products is enhanced.

Atimos Modulite contains a small amount of ethanol (alcohol). The amount in two actuations of this medicine is equivalent to less than 1 ml of wine or 1 ml of beer.

The small amount of alcohol in this medicine will not have any noticeable effects.

No specific interaction studies have been carried out with formoterol.

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.

Concomitant administration of other sympathomimetic substances such as other β₂-agonists or ephedrine may potentiate the undesirable effects of Atimos Modulite and may require titration of the dose.

The simultaneous use of formoterol and theophylline can result in mutual potentiation of effects, and there is also the likelihood of increased undesirable effects such as cardiac dysrhythmia. Compounds which themselves potentiate sympathomimetic effects, such as L-dopa, L-thyroxine, oxytocin or alcohol, can also affect cardiovascular regulation when taken at the same time as formoterol.

Administration of Atimos Modulite to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants should be performed with caution, since the action of β₂-adrenergic stimulants on the cardiovascular system may be potentiated.

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

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

β-adrenergic blockers may weaken or inhibit the effect of Atimos Modulite. Therefore, Atimos Modulite should not be given together with β-adrenergic blockers (including eye drops) unless there are compelling reasons for their use.

Pregnancy

There are no or limited amount of 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 formoterol. Treatment with formoterol 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 fetus. The potential risk for human is unknown.

Breast-feeding

It is unknown whether formoterol are excreted in human milk. In rats, small amounts of formoterol have been detected in maternal milk. Administration of formoterol 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.

A risk to the newborns/infants cannot be excluded.

Atimos Modulite has no influence on the ability to drive and use machines.

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.

Adverse reactions, which have been associated with formoterol, are listed below by system organ class and frequency. Frequency is defined as: Very Common (≥1/10), Common (≥1/100, <1/10), Uncommon (≥1/1000, <1/100), Rare (≥1/10000, <1/1000), Very rare (<1/10000).

Nausea, dysgeusia, throat irritation, hyperhidrosis, restlessness, headache, dizziness and muscle cramps may resolve spontaneously within one to two weeks of continued treatment.

Central nervous system stimulating effects have been sporadically reported following inhalation of β₂-sympathomimetics, manifesting as hyperexcitability. These effects were mainly observed in children up to 12 years of age.

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

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 at www.mhra.gov.uk/yellowcard.

Not applicable.