4.1. Therapeutic indications

Formoterol Easyhaler 12 micrograms/dose inhalation powder is indicated for use in the treatment of asthma in patients treated with inhaled corticosteroids and who also require a long-acting beta2-agonist in accordance with current treatment guidelines.

Formoterol Easyhaler 12 micrograms/dose inhalation powder is indicated also for the relief of reversible airways obstruction in patients with chronic obstructive pulmonary disease (COPD) and requiring long-term bronchodilator therapy.

4.2. Posology and method of administration

Posology

Adults (including the elderly) and adolescents (above 12 years)

Asthma

Regular maintenance therapy:

1 inhalation (12 micrograms) to be inhaled twice daily. For more severe disease this dose regimen can be increased to 2 inhalations (24 micrograms) to be inhaled twice daily.

The maximum daily dose is 4 inhalations (2 inhalations inhaled twice daily).

Chronic Obstructive Pulmonary Disease

Regular maintenance therapy: 1 inhalation (12 micrograms) to be inhaled twice daily.

The maximum daily dose is 2 inhalations (1 inhalation inhaled twice daily).

Paediatric population

Children 6 to 12 years

Asthma

Regular maintenance therapy:1 inhalation (12 micrograms) to be inhaled twice daily. The maximum daily dose is 24 micrograms.

Chronic Obstructive Pulmonary Disease

Not appropriate.

Children under the age of 6 years

Formoterol Easyhaler is not recommended for use in children under the age of 6 years.

Renal and hepatic impairment

There are no data available for use of Formoterol Easyhaler in patients with hepatic or renal impairment. As formoterol is primarily eliminated via liver metabolism an increased exposure can be expected in patients with severe liver cirrhosis.

The duration of action of formoterol has been shown to last for about 12 hours. The treatment should always aim for the lowest effective dose.

Current asthma management guidelines recommend that long-acting inhaled beta2-agonists should be used for maintenance bronchodilator therapy. They further recommend that in the event of an acute attack, a short-acting beta2-agonist should be used.

In accordance with the current asthma management guidelines, long-acting beta2-agonists may be added to the treatment regimen in patients experiencing problems with high dose inhaled steroids. Patients should be advised not to stop or change their steroid therapy when treatment with formoterol is introduced.

If the symptoms persist or worsen, or if the recommended dose of Formoterol Easyhaler fails to control symptoms (maintain effective relief), this is usually an indication of a worsening of the underlying condition.

When transferring a patient to Formoterol Easyhaler from other inhalation devices, the treatment should be individualised. The previous active substance, dose regimen, and method of delivery should be considered.

Method of administration

For inhalation use.

Precautions to be taken before handling or administering the medicinal product.

Instructions for use and handling

Easyhaler is an inspiratory flow driven inhaler, which means that when the patient inhales through the mouthpiece, the substance will follow the inspired air into the airways.

Note: It is important to instruct the patient

- to carefully read the instructions for use in the patient information leaflet which is packed together with each inhaler.

- that it is recommended to keep the device in the protective cover after opening the foil bag to enhance the stability of the product during use and make the inhaler more tamper proof.

- to shake and actuate the device prior to each inhalation.

- to breathe in forcefully and deeply through the mouthpiece to ensure that an optimal dose is delivered to the lungs.

- never to breathe out through the mouthpiece as this will result in a reduction in the delivered dose. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.

- never to actuate the device more than once without inhalation of the powder. Should this happen the patient is instructed to tap the mouthpiece onto a table top or the palm of a hand to empty the powder, and then to repeat the dosing procedure.

- to always replace the dust cap and close the protective cover after use to prevent accidental actuation of the device (which could result in either overdosing or underdosing the patient when subsequently used).

- to clean the mouthpiece with a dry cloth at regular intervals. Water should never be used for cleaning because the powder is sensitive to moisture.

- to replace Formoterol Easyhaler when the counter reaches zero even though powder can still be observed within the device.

4.3. Contraindications

Hypersensitivity to the active substance or to the excipient listed in section 6.1 (lactose monohydrate, which contains small amounts of milk proteins).

4.4. Special warnings and precautions for use

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

Asthmatic patients who require therapy with long-acting ß2-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 Easyhaler even when symptoms decrease. Should symptoms persist, or treatment with ß2-agonists need to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the maintenance therapy.

Although Formoterol Easyhaler may be introduced as add-on therapy when inhaled corticosteroids do not provide adequate control of asthma symptoms, patients should not be initiated on Formoterol Easyhaler 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 Formoterol Easyhaler. Patients should be asked to continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Formoterol Easyhaler. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Formoterol Easyhaler. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Formoterol Easyhaler should be used.

The maximum daily dose should not be exceeded. The long term safety of regular treatment at higher metered doses than 48 micrograms per day in adults with asthma, 24 micrograms per day in children with asthma and 24 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 beta2-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.

Special care and supervision, with particular emphasis on dosage limits, is required in patients receiving Formoterol Easyhaler when the following conditions may exist:

Severe hypertension, severe heart failure, ischaemic heart disease, cardiac arrhythmias, especially third degree atrioventricular block, idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, thyrotoxicosis, phaeochromocytoma, aneurysm, known or suspected prolongation of the QTc interval (QTc > 0.44 sec.; see section 4.5) and in patients treated with drugs affecting the QTc interval. Formoterol itself may induce prolongation of QTc interval.

Caution should be used when co-administering theophylline and formoterol in patients with pre-existing cardiac conditions.

Due to the hyperglycaemic effect of beta2-stimulants, additional blood glucose controls are recommended initially in diabetic patients.

Potentially serious hypokalaemia may result from beta2-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 other medicines, such as xanthine derivatives, steroids and diuretics (see section 4.5). It is recommended that serum potassium levels are monitored in such situations.

As with other inhalation therapy there is a risk of paradoxical bronchospasm. If this occurs the patient will experience an immediate increase in wheezing and shortness of breath after dosing which should be treated straightaway with a fast-acting inhaled bronchodilator. Formoterol Easyhaler inhalation powder should be discontinued immediately, the patient should be assessed and, if necessary, alternative therapy instituted (see section 4.8) .

Formoterol Easyhaler contains approx. 8 mg of lactose monohydrate per 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 Formoterol Easyhaler, as no sufficient experience is available for this group.

4.5. Interaction with other medicinal products and other forms of interaction

No specific interaction studies have been carried out with Formoterol Easyhaler.

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. In addition, levodopa, levothyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-agonists.

Concomitant administration of other sympathomimetic agents such as other beta2 -agonists or ephedrine has the potential to produce additive effects both in respect of the desirable effects and the undesirable effects of Formoterol Easyhaler. Therefore titration of the dose may be required.

Concomitant treatment with xanthine derivatives, steroids, or diuretics such as thiazides and loop diuretics may potentiate a possible hypokalaemic adverse effect of beta2-agonists. Hypokalaemia may increase susceptibility to cardiac arrhythmias in patients treated with digitalis glycosides (see section 4.4).

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

Formoterol may interact with monoamine oxidase inhibitors and should not be given to patients receiving treatment with monoamine oxidase inhibitors or for up to 14 days after their discontinuation.

Concomitant administration of formoterol and corticosteroids may increase the hyperglycaemic effect seen with these drugs.

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

Beta-adrenergic blockers may weaken or antagonise the effect of Formoterol Easyhaler. Therefore Formoterol Easyhaler should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use.

4.6. Fertility, pregnancy and lactation

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 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.

Breastfeeding

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 formoterol to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

The most commonly reported adverse events of beta2-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 given below, listed by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10 000 to < 1/1000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

Immune system disorders

Rare

Hypersensitivity reactions such as bronchospasm, severe hypotension, urticaria, angioedema, pruritus, exanthema, peripheral oedema

Metabolism and nutrition disorders

Rare

Hypokalaemia

Very rare

Hyperglycaemia

Psychiatric disorders

Uncommon

Agitation, restlessness, sleep disturbances, anxiety

Nervous system disorders

Common

Headache, tremor

Very rare

Dizziness, taste disturbance

Cardiac disorders

Common

Palpitations

Uncommon

Tachycardia

Rare

Cardiac arrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles

Very rare

Angina pectoris, prolongation of QTc interval

Vascular disorders

Very rare

Variation in blood pressure

Respiratory, thoracic and mediastinal disorders

Rare

Aggravated bronchospasm, paradoxical bronchospasm (see Section 4.4), oropharyngeal irritation

Gastrointestinal disorders

Rare

Nausea

Musculoskeletal, connective tissue and bone disorders

Uncommon

Muscle cramps, myalgia

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

Treatment with beta2-agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

Lactose monohydrate contains small amounts of milk proteins and can therefore 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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms

There is limited clinical experience on the management of overdose. An overdose would likely lead to effects that are typical of β2-agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrhythmia, nausea and vomiting.

Treatment

Supportive and symptomatic treatment is indicated. Serious cases should be hospitalised.

Use of cardioselective beta-blockers may be considered, but only subject to extreme caution since the use of beta-adrenergic blocker medication may provoke bronchospasm. Serum potassium should be monitored.