Tradename

Bufidor, Budifor

International non-proprietary name

Formoterol + Budesonide, Formetrol + Budesonide

Compound

Each dose contains:

Formoterol fumarate dihydrate equiv. formoterol fumarate 6 mcg, Budesonide 400 mcg, Propellant HFA 1341a q . s .

Dosage form

Aerosol for inhalation dosed.

Pharmacotherapeutic group

Combined bronchodilator (selective beta2-agonist + local glucocorticosteroid).

Pharmacological properties Pharmacodynamics

Combined bronchodilator. Formoterol and budesonide have different mechanisms of action and show an additive effect in reducing the frequency of exacerbations of bronchial asthma and COPD.

The special properties of formoterol and budesonide make it possible to use their combination simultaneously as maintenance therapy and for the relief of attacks, or as maintenance therapy for bronchial asthma.

Formoterol is a selective β2 -adrenergic agonist that, after inhalation, causes rapid and prolonged relaxation of bronchial smooth muscle in patients with reversible airway obstruction. The bronchodilator dose-dependent effect occurs quickly, within 1-3 minutes after inhalation and persists for at least 12 hours after taking a single dose.

Budesonide is a glucocorticosteroid (GCS), which, after inhalation, 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. Reduces the severity of edema of the bronchial mucosa, mucus production, sputum formation and hyperreactivity of the respiratory tract. The exact mechanism of the anti-inflammatory action of GCS is unknown.

The addition of formoterol to budesonide reduces the severity of asthma symptoms, improves bronchial function and reduces the frequency of exacerbations of the disease. The effect of this fixed combination on bronchial function corresponds to the effect of the combination of budesonide and formoterol alone and exceeds the effect of budesonide alone. In all cases, a short-acting beta2-adrenergic stimulant was used to relieve seizures. There was no decrease in anti-asthma effect over time. The combination is characterized by good tolerance.

Pharmacokinetics

There is no evidence of a pharmacokinetic interaction between formoterol and budesonide.

Pharmacokinetic parameters for the respective substances are comparable after the appointment of formoterol and budesonide in the form of monodrugs and in part of this combination. When administered as part of a combination , the AUC of budesonide is slightly higher, absorption occurs faster and the value of Cmax in blood plasma above. Cmax in plasma blood formoterol at administered in composition combination coincides with that for monopreparation.

Inhaled formoterol is rapidly absorbed and reaches Cmax in blood plasma 10 minutes after inhalation. The average dose of formoterol that enters the lungs after inhalation is 28-49% of the delivered dose. Systemic bioavailability is about 61% of the delivered dose.

Inhaled budesonide is rapidly absorbed and reaches Cmax in plasma after thirty min after holding inhalation. Medium dose budesonide, that got into the lungs after inhalation, is 32-44% of the delivered doses. Systemic bioavailability is approximately 49% of the delivered doses.

Plasma protein binding formoterol is 50%, budesonide - 90%. Vd formoterol is about 4 l / kg, budesonide - 3 l / kg.

Formoterol is inactivated by conjugation (active O-demethylated metabolites are formed, mainly in the form of inactivated conjugates). Budesonide undergoes intensive biotransformation (about 90%) during the "first pass" through the liver with the formation of metabolites with low glucocorticoid activity. Glucocorticoid activity of the main metabolites of 6- β -hydroxybudesonide and 16- α -hydroxyprednisolone does not exceed 1% of the similar activity of budesonide. There is no evidence of metabolite interactions or substitution reactions between budesonide and formoterol.

The main part of the dose of formoterol is metabolized in the liver and then excreted by the kidneys. After inhalation, 8-13% of the delivered dose of formoterol is excreted unchanged in the urine. Formoterol has a high systemic clearance (approximately 1.4 l / min); T 1/2 of the drug is on average 17 h.

Budesonide is metabolized mainly with the participation of the CYP 3 A 4 enzyme. Budesonide metabolites are excreted in the urine unchanged or in the form of conjugates. Only a small amount of unchanged budesonide is found in the urine. Budesonide has a high systemic clearance (approximately 1.2 l/min).

Indications for use

Bronchial asthma, insufficiently controlled by inhalation GCS and short-acting beta2-agonists or adequately controlled by inhaled corticosteroids and long-acting beta2-agonists actions.

symptomatic therapy patients With severe COPD (FEV1 <50% from expected level) and with a history of recurrent exacerbations that have severe symptoms of the disease, despite long-term bronchodilator therapy. actions.

Contraindications

Hypersensitivity to active substances or excipients; childhood.

Dosage and administration

Inhalation.

Adults (including the elderly)

Bronchial asthma

Permanent maintenance therapy: 1 inhalation 2 times a day; some patients may require 2 inhalations 2 times a day. The maximum daily dose for continuous use is 4 inhalations.

If necessary, it is possible to use additional doses, in addition to those prescribed for continuous maintenance therapy, to relieve symptoms up to a maximum total daily dose of 6 inhalations (supporting plus taken as needed). Do not take more than 3 inhalations simultaneously. However frequent (more two once in day and/or more than for 2 days a week) use, or use in doses exceeding those recommended for continuous maintenance therapy, is a sign of suboptimal control of the course of bronchial asthma and requires revision scheme treatment.

Prevention of exercise-induced bronchospasm

1 inhalation approximately 15 minutes before exercise. In severe asthma, 2 inhalations may be required. Do not exceed the maximum total daily dose (6 inhalations).

COPD

one inhalation 2 times a day day.

The use of the drug Budifor consists of three steps: open, inhale and close, which are described below.

Open: Hold the Budifor with the mouthpiece cap down. Open the mouthpiece cover to its full opening by flipping it down until it clicks.

Inhale: Exhale completely, close the mouthpiece tightly with your lips and inhale deeply, hold your breath for 5-10 seconds.

Close: Remove the mouthpiece from your mouth, exhale gently and close the mouthpiece lid.

Special instructions and precautions

Before stopping treatment, it is recommended to gradually reduce the dose. It is not recommended to abruptly cancel treatment.

The combination of formoterol + budesonide is not used for the initial selection of therapy in the early stages of the treatment of bronchial asthma.

Formoterol may cause prolongation of the QT interval .

An increase in the frequency of taking bronchodilators as emergency drugs indicates a deterioration in the course of the underlying disease and serves as the basis for revising the tactics of treating bronchial asthma. Sudden and progressive worsening of asthma or COPD symptom control is a potentially life-threatening condition and requires urgent medical attention. In this situation, consideration should be given to increasing the dose of corticosteroids or adding systemic anti-inflammatory therapy, for example, a course of oral corticosteroids or antibiotic treatment in case of infection. Patients are advised to carry emergency medications (short-acting beta2-adrenergic agonists) with them at all times. The patient's attention should be drawn to the need to regularly take the drug containing the combination of formoterol + budesonide in accordance with the selected dose, even in cases of no symptoms of the disease.

Treatment should not be started during an exacerbation or a significant deterioration in the course of bronchial asthma.

As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after a dose of the combination drug. In this connection, it is necessary to stop therapy, revise the tactics of treatment and, if necessary, prescribe alternative therapy.

A systemic effect can occur when taking any inhaled corticosteroids, especially when taking drugs in high doses for a long period of time. The manifestation of systemic action is less likely during inhalation therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, decreased bone mineral density, cataracts and glaucoma.

Due to the potential effect of inhaled corticosteroids on bone mineral density, special attention should be paid to patients taking high doses of the drug for a long period with risk factors for osteoporosis.

If there is reason to believe that adrenal function was impaired during previous systemic corticosteroid therapy, precautions should be taken when transferring patients to treatment with a combination of formoterol + budesonide.

The need for the use and dose of inhaled corticosteroids in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system should be reconsidered.

With the joint appointment of beta2-agonists with drugs that can cause or enhance the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, it is possible to increase the hypokalemic effect of beta2-agonists.

Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve attacks during an exacerbation of severe bronchial asthma, because. the risk of developing hypokalemia increases against the background of hypoxia and in other conditions, when the likelihood of developing a hypokalemic effect increases. In such cases, it is recommended to control the content of potassium in the serum.

During treatment, the concentration of glucose in the blood should be monitored in patients with diabetes mellitus.

Influence on the ability to management transport means and Mechanisms The combination of formoterol + budesonide may have a minor effect in the manifestation of side effects. Care must be taken when driving vehicles and mechanisms during the treatment period.

Use during pregnancy and during breastfeeding

During pregnancy, the combination of formoterol + budesonide should be used only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus. Budesonide should be used at the lowest effective dose required to maintain adequate control of asthma symptoms.

Inhaled budesonide is excreted in breast milk, however, when used in therapeutic doses, no effect on the child was noted. It is not known whether formoterol is excreted in breast milk in women. The combination of formoterol + budesonide should only be used in breastfeeding women if the expected benefit to the mother outweighs any potential risk to the baby.

Interaction with other drugs

Taking ketoconazole at a dose of 200 mg 1 time / day increases the plasma concentration of budesonide when administered orally (single dose of 3 mg) when they are co-administered, on average, 6 times. With the appointment of ketoconazole 12 hours after taking budesonide, the concentration in the plasma of the latter increased, on average, 3 times. There is no information on such an interaction with budesonide during its inhalation use, however, a noticeable increase in the concentration of the drug in the blood plasma should be expected. Because data for there are no recommendations on dose selection, the above combination of drugs should be avoided. If possible, the time intervals between the appointment of ketoconazole and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent inhibitors of CYP 3 A 4 are also likely to significantly increase the concentration of budesonide in plasma.

Blockers of β 2-adrenergic receptors are able to reduce the intensity of the action of formoterol. The combination of formoterol + budesonide should not be administered simultaneously with beta-blockers (including eye drops), except in cases of emergency.

Co-administration of a combination of formoterol + budesonide and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors, tricyclic antidepressants may prolong the QT interval and increase the risk of ventricular arrhythmias.

In addition, levodopa, levothyroxine, oxytocin and alcohol can reduce the tolerance of the heart muscle to beta2-agonists.

The simultaneous use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, may cause an increase HELL. Exists elevated risk development arrhythmias at patients during general anesthesia with drugs of halogenated hydrocarbons. With the simultaneous use of a combination of budesonide / formoterol and other beta-adrenergic drugs, the side effects of formoterol may be increased. As a result of the use of beta2-adrenergic agonists, hypokalemia may develop, which may be aggravated by concomitant treatment with xanthine derivatives, corticosteroids, or diuretics. Hypokalemia may increase the susceptibility to arrhythmias in patients accepting heart glycosides.

Side effect

From the nervous system: headache, psychomotor agitation, anxiety, nausea, dizziness, sleep disturbances, depression, taste disturbances.

From the side of the cardiovascular system: palpitations, tachycardia, atrial fibrillation, supraventricular tachycardia, extrasystole, angina, fluctuations in blood pressure.