- formoterol fumarate dihydrate
POM: Prescription only medicine
This information is intended for use by health professionals
PosologyADULTS (INCLUDING OLDER PEOPLE) AND ADOLESCENTS (ABOVE 12 YEARS)
AsthmaRegular 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 DiseaseRegular maintenance therapy: 1 inhalation (12 micrograms) to be inhaled twice daily. The maximum daily dose is 2 inhalations (1 inhalation inhaled twice daily).
Paediatric populationCHILDREN 6 to 12 YEARS
AsthmaRegular maintenance therapy:1 inhalation (12 micrograms) to be inhaled twice daily. The maximum daily dose is 24 micrograms.
Chronic Obstructive Pulmonary DiseaseNot appropriate.CHILDREN UNDER THE AGE OF 6 YEARSFormoterol Easyhaler is not recommended for use in children under the age of 6 years.
Renal and hepatic impairmentThere 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 administrationFor inhalation use. Precautions to be taken before handling or administering the medicinal product.
Instructions for use and handlingEasyhaler 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 laminate pouch 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.
PregnancyThere 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.
BreastfeedingIt 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.
|Immune system disorders||Rare||Hypersensitivity reactions such as bronchospasm, severe hypotension, urticaria, angioedema, pruritus, exanthema, peripheral oedema|
|Metabolism and nutrition disorders||Rare||Hypokalaemia|
|Psychiatric disorders||Uncommon||Agitation, restlessness, sleep disturbances, anxiety|
|Nervous system disorders||Common||Headache, tremor|
|Very rare||Dizziness, taste disturbance|
|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|
|Musculoskeletal, connective tissue and bone disorders||Uncommon||Muscle cramps, myalgia|
SymptomsThere is limited clinical experience on the management of overdose. An overdose would likely lead to effects that are typical of beta2-agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrhythmia, nausea and vomiting.
TreatmentSupportive 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.
Mechanism of actionFormoterol is a potent selective beta2-adrenergic stimulant. It exerts a bronchodilator effect in patients with reversible airways obstruction. The effect sets in rapidly (within 1-3 minutes) and is still significant 12 hours after inhalation.
Clinical efficacy and safetyIn man, formoterol has been shown to be effective in preventing bronchospasm induced by exercise and methacholine.Formoterol has been studied in the treatment of conditions associated with COPD, and has been shown to improve symptoms and pulmonary function. Formoterol acts on the reversible component of the disease.
AbsorptionAs reported for other inhaled drugs, it is likely that about 80 % of formoterol administered from the Easyhaler inhaler will be swallowed and then absorbed from the gastrointestinal tract. This means that the pharmacokinetic characteristics of the oral formulation largely apply also to the inhalation powder. Following inhalation of therapeutic doses, formoterol cannot be detected in the plasma using current analytical methods. Absorption is both rapid and extensive: At a higher than therapeutic dose (120 micrograms), the peak plasma concentration is observed at 5 minutes post inhalation whilst at least 65 % of a radiolabelled 80 micrograms oral dose is absorbed, and oral doses of up to 300 micrograms are readily absorbed with the peak concentrations of unchanged formoterol at 0.5-1 hour. In COPD patients treated for 12 weeks with formoterol fumarate 12 or 24 micrograms b.i.d. the plasma concentrations of formoterol ranged between 11.5 and 25.7 pmol/L and 23.3 and 50.3 pmol/L respectively at 10 minutes, 2 hours and 6 hours post inhalation.The pharmacokinetics of formoterol appear linear in the range of oral doses investigated, i.e. 20-300 micrograms. Repeated oral administration of 40-160 micrograms daily does not lead to significant accumulation of the drug. The maximum excretion rate after administration of 12-96 micrograms is reached within 1-2 hours of inhalation.After 12 weeks administration of 12 micrograms or 24 micrograms formoterol powder b.i.d., the urinary excretion of unchanged formoterol increased by 63-73 % in adult patients and by 18-84 % in children, suggesting a modest and self-limiting accumulation of formoterol in plasma after repeated dosing. Studies investigating the cumulative urinary excretion of formoterol and/or its (R,R) and (S,S)-enantiomers, after inhalation of dry powder (12-96 micrograms) or aerosol formulations (12- 96 micrograms), showed that absorption increased linearly with the dose.
DistributionThe plasma protein binding of formoterol is 61- 64 % (34 % primarily to albumin). There is no saturation of binding sites in the concentration range reached with therapeutic doses.
BiotransformationFormoterol is eliminated primarily by metabolism, direct glucuronidation being the major pathway of biotransformation, with O-demethylation followed by further glucuronidation being another pathway. Multiple CYP450 isoenzymes (2D6, 2C19, 2C9, and 2A6) catalyze the transformation and so consequently the potential for metabolic drug-drug interaction is low. The kinetics of formoterol are similar after single and repeated administration, indicating no auto-induction or inhibition of metabolism.
EliminationElimination of formoterol from the circulation seems to be polyphasic; the apparent half-life depends on the time interval considered. On the basis of plasma or blood concentrations up to 6, 8 or 12 hours after oral administration, an elimination half-life of about 2-3 hours was determined. From urinary excretion rates between 3 and 16 hours after inhalation, a half-life of about 5 hours was calculated.After inhalation, plasma formoterol kinetics and urinary excretion rate data in healthy volunteers indicate a biphasic elimination, with the terminal elimination half-lives of the (R,R)- and (S,S)-enantiomers being 13.9 and 12.3 hours, respectively. Approximately 6.4-8 % of the dose was recovered in the urine as unchanged formoterol, with the (R,R) and (S,S)-enantiomers contributing 40 % and 60 % respectively. After a single oral dose of 3H-formoterol, 59-62 % of the dose was recovered in the urine and 32-34 % in the faeces. Renal clearance of formoterol is 150 ml/min.In adult asthmatics, approximately 10 % and 15-18 % of the dose was recovered in the urine as unchanged and conjugated formoterol, respectively, after multiple doses of 12 and 24 micrograms. In children, approximately 6 % and 6.5-9 % of the dose was recovered in the urine as unchanged and conjugated formoterol, respectively, after multiple doses of 12 and 24 micrograms. As in healthy volunteers, the (R,R) and (S,S)-enantiomers contributed approximately 40 % and 60 % of unchanged drug excreted in the urine of adults, respectively, and there was no relative accumulation of one enantiomer over the other after repeated dosing.
Before the first use store in the unopened laminate pouch.For storage conditions after first opening of the medicinal product, see section 6.3
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