Directions for use and doses
The drug is not intended for oral administration.
The dose of Formoterol-native is selected individually depending on the needs of the patient. The lowest dose that provides a therapeutic effect should be used. When control of bronchial asthma symptoms is achieved during therapy with Formoterol-native, it is necessary to consider the possibility of gradually reducing the dose of the drug. Reducing the dose of Formoterol-native is carried out under regular medical supervision of the patient’s condition. The drug consists of capsules with powder for inhalation, which should be used only with the help of a special device - the Inhaler CDM® inhaler, which is included in the package. Bronchial asthma The dose of the drug Formoterol-native for regular maintenance therapy (is 12-24 mcg (contents 1-2 capsules) 2 times / day. Formoterol-native should be used only as additional therapy to inhaled corticosteroids. The maximum recommended dose should not be exceeded of the drug 48 mcg/day (contents 4 capsules). Considering that the maximum daily dose of the drug Formoterol-native is 48 mcg, if necessary, you can additionally use 12-24 mcg/day to relieve the symptoms of bronchial asthma. If there is a need for additional doses of the drug Formoterol-native ceases to be episodic (for example, it becomes more often than 2 days a week), this may indicate a worsening of bronchial asthma, you should consult a doctor. Against the background of exacerbation of bronchial asthma, you should not start treatment with Formoterol-native or change the dosage of the drug Formoterol-native should not be used to relieve acute attacks of bronchial asthma. Prevention of bronchospasm caused by physical activity or inevitable exposure to a known allergen. Formoterol-native should be used in a dose of 12 mcg (contents 1 cap.) 15 minutes before expected contact with the allergen or before exercise . Additional inhalations of the drug should not be carried out over the next 12 hours. Prevention of severe bronchospasms Patients with a history of severe bronchospasms may require a single inhalation at a dose of 24 mcg (contents of 2 capsules). COPD The dose of Formotsrol-native for regular maintenance therapy of COPD is 12-24 mcg (contents of 1-2 capsules) 2 times a day.
Teenagers (12-17 years):
Formisonide native 80 mcg + 4.5 mcg and 160 mcg + 4.5 mcg 1-2 inhalations twice a day
Formisonide native 320 mcg + 9 mcg 1 inhalation twice a day
Children over 6 years old:
Formisonide native 80 mcg + 4.5 mcg 1-2 inhalations twice a day.
Pharmacological group
Combined bronchodilator (selective β2-adrenergic agonist + local glucocorticosteroid).
Pharmacodynamics
Formisonide®-native is a combination drug containing formoterol and budesonide, which have different mechanisms of action and exhibit an additive effect on the severity of symptoms of bronchial asthma (BA), improving lung function and reducing the frequency of exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). The special properties of budesonide and formoterol make it possible to use their combination in the treatment of bronchial asthma simultaneously as maintenance therapy and to relieve attacks, or as maintenance therapy.
Budesonide, a glucocorticosteroid (GCS), after inhalation in recommended doses, has a rapid (within several hours) and dose-dependent anti-inflammatory effect on the respiratory tract, reducing the severity of symptoms and the frequency of exacerbations of bronchial asthma. When prescribing inhaled budesonide, there is a lower incidence of serious adverse effects than when using systemic corticosteroids. Budesonide reduces the severity of edema of the bronchial mucosa, mucus production, sputum formation and airway hyperresponsiveness. The exact mechanism of the anti-inflammatory effect of GCS is unknown.
Formoterol is a selective β2-adrenergic agonist (selective β2-adrenergic receptor agonist) that causes rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator effect is dose-dependent, occurs within 1-3 minutes after inhalation and persists for at least 12 hours after taking a single dose.
The effect of the drug Formisonide®-native on lung function corresponds to the effect of the combination of budesonide and formoterol monotherapy and exceeds the effect of budesonide alone.
Pharmacokinetics
The pharmacokinetic parameters for the corresponding substances are comparable after the administration of budesonide and formoterol as single agents and as part of a combination. For budesonide, when administered as part of a combination drug, the area under the concentration-time curve (AUC) is slightly larger, the drug is absorbed faster and the maximum plasma concentration is higher.
For formoterol, when administered as part of a combination drug, the maximum concentration in blood plasma coincides with that for the single drug.
32-44% of the administered dose of inhaled budesonide is deposited in the lungs, where it is rapidly absorbed and reaches its maximum concentration (Cmax) after 20-30 minutes. Systemic bioavailability is approximately 39-49% of the delivered dose. The cumulation index for budesonide (when taking 2 inhalations 2 times a day) is 1.32.
After oral administration of budesonide, the peak Cmax in plasma is observed after 1-2 hours. Absolute systemic bioavailability is 6-13% of the inhaled dose.
28-49% of the dose of inhaled formoterol is deposited in the lungs, where it is quickly absorbed and reaches maximum concentration 5-10 minutes after inhalation. Systemic bioavailability is approximately 61% of the delivered dose. The accumulation index for formoterol (when taking 2 inhalations 2 times a day) is 1.77.
Distribution
Budesonide has almost no binding to corticosteroid binding globulin. Plasma protein binding is constant for budesonide in the concentration range (1-100 nmol/l) for both recommended and exceeded doses, and is approximately 90%.
The volume of distribution of budesonide is approximately 3 l/kg.
Budesonide passes into breast milk.
Formoterol: over the entire concentration range of 10-500 nmol/l, binding to plasma proteins for the RR and SS enantiomers of formoterol is 46% and 58%, respectively, with an average of 50%.
The volume of distribution is formoterol – 4 l/kg.
Metabolism
Budesonide undergoes intense biotransformation (about 90%) during the “first pass” through the liver with the formation of metabolites with low glucocorticosteroid activity. The metabolism of budesonide is carried out primarily with the participation of the CYP3A4 isoenzyme. The glucocorticosteroid activity of the main metabolites - 6-β-hydroxybudesonide and 16-α-hydroxyprednisolone - does not exceed 1% of the similar activity of budesonide.
Formoterol is metabolized mainly in the liver with the participation of the enzymes CYP2D6 and CYP2C by conjugation to form active O-demethylated metabolites, mainly inactivated conjugates. Secondary metabolism involves molecular breakdown and sulfate conjugation.
There is no evidence of metabolite interactions or substitution reactions between budesonide and formoterol.
Removal
Budesonide is excreted in urine and feces in the form of conjugates and only in small quantities unchanged. Budesonide has a high systemic clearance (approximately 1.2 L/min). The half-life (T 1/2) of budesonide ranges from 2 to 3.6 hours.
Formoterol: After inhalation, 8-13% of the delivered dose of formoterol is excreted unchanged in urine (62%) and feces (24%). Formoterol has a high systemic clearance (approximately 1.4 L/min). The half-life (T 1/2) averages 17 hours.
Pharmacokinetics in special clinical situations
The pharmacokinetics of formoterol in patients with renal failure have not been studied. Plasma concentrations of budesonide and formoterol may be increased in patients with liver disease.
Overdose
Symptoms: an overdose of formoterol can probably lead to the development of phenomena characteristic of an overdose of beta2-adrenergic agonists or an increase in the manifestation of side effects: chest pain, palpitations, tachycardia up to 200 beats/min, ventricular arrhythmias, increased or decreased blood pressure, dryness in the mouth, nausea, vomiting, headache, dizziness, tremor, nervousness, weakness, anxiety, drowsiness, metabolic acidosis, hypokalemia, hyperglycemia, convulsions. As with all inhaled beta2-agonists, an overdose of formoterol can cause cardiac arrest and death. Treatment: maintenance and symptomatic therapy is indicated. In serious cases, hospitalization is necessary. The use of cardioselective beta2-blockers may be considered, but only under close medical supervision and with extreme caution. the use of such drugs may cause bronchospasm. Monitoring of cardiac indicators is recommended.
Side effects
No increase in the incidence of adverse reactions was observed during the co-administration of budesonide and formoterol.
Adverse reactions are distributed according to frequency of occurrence. The following criteria were used to assess the frequency: very often (>1/10), often (from 1/100 to 1/10), infrequently (from 1/1000 to 1/100), rarely (from 1/10000 to 1/1000 ), very rare (< 1/10000), (including isolated reports).
Infectious and parasitic diseases: often - rhinopharyngitis, nasal congestion, sinusitis, upper respiratory tract infections, bronchitis, oropharyngeal candidiasis (candidiasis of the oral mucosa and larynx).
Immune system disorders: rarely - anaphylactic reactions, including angioedema (Quincke's edema); bronchospasm, including paradoxical.
Endocrine system disorders: rarely – hypokalemia; very rarely - hyperglycemia, symptoms of systemic glucocorticosteroid effects (including hypocortisolism, hypercortisolism.)
Mental disorders: infrequently – psychomotor agitation, restlessness, anxiety, dizziness, sleep disturbances; very rarely - depression, behavioral disorders, aggressive behavior, nervousness, taste disturbances.
Central nervous system disorders: often – headache.
Visual disturbances: very rarely - cataracts, glaucoma (with long-term use of high doses), increased intraocular pressure.
Cardiac disorders: often – palpitations; infrequently - tachycardia; rarely - arrhythmias, including atrial fibrillation, supraventricular tachycardia, extrasystole; very rarely - angina pectoris, atrial and ventricular tachyarrhythmia.
Vascular disorders: very rarely - changes in blood pressure (hypotension, arterial hypertension).
Disorders of the respiratory system, chest and mediastinal organs: often - irritation in the throat, cough, hoarseness; rarely – dysphonia (disappearing after stopping therapy or reducing the dose of the drug).
Gastrointestinal disorders: often – discomfort in the stomach; rarely - vomiting; very rarely - nausea, dysphagia (impaired swallowing).
Disturbances of the skin and subcutaneous tissues: infrequently - bruising; rarely – urticaria, itching, dermatitis, rash; very rarely - redness of the facial skin.
Musculoskeletal and connective tissue disorders: often – tremor; infrequently – muscle cramps; rarely – osteoporosis (decreased bone mineral density), back pain.
The systemic effect of inhaled corticosteroids can be observed when taking the drug in high doses for a long time.
The use of β2-adrenergic agonists can lead to an increase in the blood levels of insulin, free fatty acids, glycerol, and ketone derivatives.
If any of the side effects indicated in the instructions get worse or you notice any other manifestations not listed in the instructions, tell your doctor.
special instructions
Anti-inflammatory therapy In patients with bronchial asthma, native formoterol should be used only as an additional treatment in case of insufficient control of symptoms during monotherapy with inhaled corticosteroids or in severe forms of the disease requiring the use of a combination of inhaled corticosteroids and a long-acting β2-adrenergic receptor agonist. Formoterol native should not be used with other long-acting β2-adrenergic receptor agonists. When prescribing the drug Formoterol-native, it is necessary to assess the condition of patients regarding the adequacy of the anti-inflammatory therapy that they receive. After starting treatment with Formoterol-native, patients should be advised to continue anti-inflammatory therapy without changes, even if improvement is noted. To relieve an acute attack of bronchial asthma, β2-adrenergic receptor agonists should be used. If the condition suddenly worsens, patients should seek medical help immediately. Hypokalemia Treatment with beta2-agonists, including Formoterol native, may result in the development of potentially serious hypokalemia. Hypokalemia may increase the risk of developing arrhythmias. Because This effect of the drug Formoterol-native can be enhanced by hypoxia and concomitant treatment; special caution should be observed in patients with severe bronchial asthma. In these cases, regular monitoring of serum potassium concentration is recommended. Paradoxical bronchospasm Like other inhaled drugs, Formoterol native can cause paradoxical bronchospasm. In this case, the drug should be discontinued immediately and alternative treatment should be prescribed. The use of formoterol in a dose exceeding 54 mcg/day (more than 4 inhalations) may lead to positive doping tests. Effects on the ability to drive motor vehicles and other vehicles, to work with moving mechanisms There are no data on the effect of the drug Formoterol-native on the ability to drive motor vehicles and operate machinery. In the event of the development of such adverse reactions as dizziness, tremors, convulsions or muscle spasms, it is necessary to refrain from driving vehicles and operating machinery, as well as from engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Contraindications
- Hypersensitivity to budesonide, formoterol or any other excipient of the drug
- Galactose intolerance, lactase deficiency or glucose-galactose malabsorption
- Age up to 18 years.
Carefully
Formisonide®-native should be used with caution in patients with pulmonary tuberculosis (active and inactive form), with fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, hypothyroidism, pheochromocytoma, diabetes mellitus, ketoacidosis, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any location or other severe cardiovascular diseases (coronary heart disease, tachyarrhythmia or severe heart failure), prolongation of the QTc interval (taking formoterol can cause prolongation of the QTc interval), cirrhosis of the liver, cataracts, glaucoma, convulsive disorders, allergies a history of lactose and milk protein (since partial ingestion of the drug during inhalation is possible).
