Duoresp spiromax 160 mcg plus 4.5 mcg powder for inhalation 120 doses

pharmachologic effect

Combined bronchodilator drug. DuoResp Spiromax contains formoterol and budesonide, which have different mechanisms of action and exhibit an additive effect in reducing the frequency of exacerbations of bronchial asthma and COPD.

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

Budesonide is a corticosteroid that, 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 airway hyperreactivity. The exact mechanism of the anti-inflammatory effect of GCS is unknown.

Formoterol is a selective β2-adrenergic agonist that, following inhalation, causes rapid and long-lasting 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.

The addition of formoterol to budesonide reduces the severity of symptoms of bronchial asthma, improves bronchial function and reduces the frequency of exacerbations of the disease.

The effect of DuoResp Spiromax on bronchial function corresponds to the effect of the combination of budesonide and formoterol monotherapy and exceeds the effect of budesonide alone. In all cases, a short-acting beta2-agonist agonist was used to relieve attacks. There was no decrease in anti-asthmatic effect over time. The drug is well tolerated.

Indications for use

• bronchial asthma, insufficiently controlled by taking inhaled corticosteroids and short-acting beta2-agonists or adequately controlled by inhaled corticosteroids and long-acting beta2-agonists;
• COPD is a symptomatic treatment in patients with severe COPD (FEV1 <50% predicted level) and with a history of recurrent exacerbations who have severe symptoms of the disease despite therapy with long-acting bronchodilators.

Directions for use and doses

• Bronchial asthma

The drug DuoResp Spiromax is not intended for the initial treatment of intermittent and mild persistent bronchial asthma. Selection of the dose of the drugs included in the drug DuoResp Spiromax occurs individually and depending on the severity of the disease. This must be taken into account not only when starting treatment with combination drugs, but also when changing the maintenance dose of the drug.

In the event that individual patients require a different combination of doses of active components than in the drug DuoResp Spiromax, beta2-agonists and/or corticosteroids should be prescribed in separate inhalers.

Patients should visit their doctor regularly to monitor the optimal dose of DuoResp Spiromax. The dose should be reduced to the lowest dose that maintains optimal control of asthma symptoms. After achieving optimal control of bronchial asthma when taking the drug 2 times a day, it is recommended to titrate the dose to the minimum effective, up to taking the drug 1 time a day, in cases where, in the opinion of the doctor, the patient requires maintenance therapy in combination with a long-acting bronchodilator .

• Adults (18 years and older)

The drug DuoResp Spiromax 160/4.5 mcg/dose as maintenance therapy

1-2 inhalations 2 times/day. If necessary, the dose can be increased to 4 inhalations 2 times a day. The patient must always have with him a separate inhaler with a short-acting beta2-adrenergic agonist to relieve attacks. An increase in the frequency of use of short-acting beta2-agonists is an indicator of deterioration in overall disease control and requires a review of anti-asthmatic therapy.

The drug DuoResp Spiromax 160/4.5 mcg/dose as maintenance therapy and for the relief of attacks

DuoResp Spiromax can be prescribed both as continuous maintenance therapy and as on-demand therapy when attacks occur. As a maintenance therapy and for the relief of attacks, it is especially indicated for patients with:

- insufficient control over bronchial asthma and the need for frequent use of drugs to relieve attacks;

- a history of exacerbations of bronchial asthma that required medical intervention.

Careful monitoring of dose-related side effects is required in patients using large numbers of inhalations to relieve attacks.

The recommended dose for maintenance therapy is 2 inhalations/day: 1 inhalation in the morning and evening, or 2 inhalations 1 time/day only in the morning or only in the evening. For some patients, a maintenance dose of DuoResp Spiromax 160/4.5 mcg/dose may be prescribed - 2 inhalations 2 times a day. If symptoms occur, 1 additional inhalation is necessary. With a further increase in symptoms within a few minutes, 1 additional inhalation is prescribed, but no more than 6 inhalations to relieve 1 attack.

Usually it is not necessary to prescribe more than 8 inhalations per day, but you can increase the number of inhalations to 12 per day for a short time. Patients receiving more than 8 inhalations per day are advised to seek medical help to review therapy.

Drug DuoResp Spiromax 320/9 mcg/dose

Prescribe 1 inhalation 2 times a day. If necessary, the dose can be increased to 2 inhalations 2 times a day.

After achieving optimal control of the symptoms of bronchial asthma while taking the drug 2 times a day, it is possible to reduce the dose to the lowest effective dose, up to 1 time a day.

• COPD

Adults (18 years and older)

DuoResp Spiromax 160/4.5 mcg/dose 2 inhalations 2 times a day.

DuoResp Spiromax 320/9 mcg/dose 1 inhalation 2 times/day.

Buy Duoresp Spiromax powder for inhalation 160mcg+4.5mcg/dose 120doses in pharmacies

Trade name:

DuoResp Spiromax

International nonproprietary or generic name:

budesonide + formoterol

Dosage form:

dosed powder for inhalation

Composition 1 delivered dose contains:

active ingredients: budesonide (micronized) 160 mcg/320 mcg, formoterol fumarate dihydrate (micronized) 4.5 mcg/9 mcg;

excipient: lactose monohydrate* 5 mg/10 mg.

*The target amount of lactose monohydrate in the delivered dose is indicated (it is approximate).

Description

A white or off-white powder without visible lumps or inclusions, placed in a multi-dose powder inhaler with a translucent red mouthpiece cap. The inhaler must be free of visible damage or leakage of powder. The dosing indicator window should show #120 for the 160/4.5 mcg/dose dosage and #60 for the 320/9 mcg/dose dosage.

Pharmacotherapeutic group:

combined bronchodilator (selective beta2-adrenergic agonist + local glucocorticosteroid)

Pharmacological properties

Pharmacodynamics

The drug DuoResp Spiromax contains formoterol and budesonide, which have different mechanisms of action and exhibit an additive effect in 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 simultaneously as maintenance therapy and for the relief of attacks or as maintenance therapy for bronchial asthma.

Budesonide

Budesonide is a glucocorticosteroid (GCS), which, after inhalation, has a rapid (within several hours) and dose-dependent anti-inflammatory effect on the airways, 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 airway hyperreactivity. The exact mechanism of the anti-inflammatory effect of GCS is unknown.

Formoterol

Formoterol is a selective β2-adrenergic receptor agonist that, following inhalation, causes rapid and long-lasting 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 + Formoterol

Bronchial asthma

Clinical effectiveness as maintenance therapy

The addition of formoterol to budesonide reduces the severity of asthma symptoms, improves lung function and reduces the frequency of exacerbations of the disease.

The effect of DuoResp Spiromax on lung function corresponds to the effect of the combination of budesonide and formoterol monotherapy and exceeds the effect of budesonide alone. In all cases, a short-acting β2-agonist agonist was used to relieve attacks. There was no decrease in the anti-asthmatic effect over time. The drug is well tolerated.

Clinical effectiveness as maintenance therapy and for the relief of attacks (only for dosage 160/4.5)

During the observation of 4447 patients receiving budesonide/formoterol therapy as maintenance therapy and for the relief of attacks for 6 to 12 months, a statistically and clinically significant decrease in the number of severe exacerbations was noted, an increase in the period of time until the onset of the first exacerbation compared with the combination budesonide/formoterol or budesonide as maintenance therapy and a β2-agonist to relieve attacks. Effective control of disease symptoms, pulmonary function, and a decrease in the frequency of inhalation prescriptions to relieve attacks were also noted. There was no development of tolerance to the prescribed therapy. In patients who sought medical help due to the development of an acute attack of bronchial asthma, after inhalation of budesonide/formoterol, relief of symptoms (relief of bronchospasm) occurred as quickly and effectively as after the administration of salbutamol and formoterol.

COPD

In two 12-month studies in patients with moderate to severe COPD (baseline: pre-bronchodilator FEV1 < 50% predicted; median post-bronchodilator FEV1 = 42% predicted) with DuoResp Spiromax, there was a significant reduction in the incidence of exacerbations of the disease compared with patients receiving DuoResp Spiromax. those receiving only formoterol or placebo as therapy (mean exacerbation rate 1.4 compared with 1.8-1.9 in the placebo/formoterol group). There were no differences observed between taking DuoResp Spiromax and formoterol on forced expiratory volume in the first second (FEV1).

Pharmacokinetics

Suction. The drug DuoResp Spiromax is bioequivalent to the corresponding monopreparations with regard to the systemic action of budesonide and formoterol. Despite this, there was a slight increase in cortisol suppression after taking the combination drug compared to the single drug. This difference does not have an impact on clinical safety. There is no evidence of a pharmacokinetic interaction between budesonide and formoterol.

Pharmacokinetic parameters for the corresponding substances are comparable after the administration of budesonide and formoterol in the form of single drugs and as part of the drug DuoResp Spiromax. 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.

Inhaled budesonide is rapidly absorbed and reaches maximum plasma concentration 30 minutes after inhalation. The average dose of budesonide that enters the lungs after inhalation is 32-44% of the delivered dose. Systemic bioavailability is approximately 49% of the delivered dose. In children aged 6 to 16 years, the average dose of budesonide entering the lungs after inhalation does not differ from that in adult patients (the final concentration of the drug in the blood plasma was not determined).

Inhaled formoterol is rapidly absorbed and reaches maximum concentration 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 approximately 61% of the delivered dose.

Distribution. Approximately 50% of formoterol and 90% of budesonide are bound to plasma proteins. The volume of distribution for formoterol is about 4 l/kg and for budesonide 3 l/kg. Formoterol is inactivated by conjugation (active O-demethylated metabolites are formed, mainly in the form of inactivated conjugates). Budesonide undergoes intense biotransformation (about 90%) during the first passage through the liver with the formation of metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the main metabolites 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.

Metabolism. The bulk 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); The half-life of the drug averages 17 hours.

Budesonide is metabolized primarily with the participation of the CYP3A4 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).

The pharmacokinetics of formoterol in children and in patients with renal failure have not been studied. Plasma concentrations of budesonide and formoterol may be increased in patients with liver disease.

Indications for use

160/4.5 mcg/dose:

— Bronchial asthma, to achieve general control of the disease, including prevention and relief of symptoms, and reducing the risk of exacerbations. DuoResp Spiromax is suitable for the treatment of bronchial asthma of any severity, if it is advisable to use inhaled glucocorticosteroids. — Chronic obstructive pulmonary disease (COPD) (symptomatic therapy in patients with severe COPD with post-bronchodilator FEV1 < 70% of predicted and with a history of exacerbations, despite regular therapy with long-acting bronchodilators).

Contraindications for use

- Hypersensitivity to budesonide, formoterol or inhaled lactose. — Children under 18 years of age. - Lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Carefully

Pulmonary tuberculosis (active or inactive form); fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, decreased adrenal function, uncontrolled hypokalemia, hypertrophic obstructive cardiomyopathy, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any location or other severe cardiovascular diseases (coronary artery disease) heart disease, tachyarrhythmia or severe heart failure), prolongation of the QT interval (taking formoterol may cause prolongation of the QT interval).

Use during pregnancy and breastfeeding

Pregnancy

There are no clinical data on the use of DuoResp Spiromax or the combined use of formoterol and budesonide during pregnancy.

During pregnancy, DuoResp Spiromax should be used only in cases where the benefit of the drug outweighs the potential risk to the fetus. The lowest effective dose of budesonide needed to maintain adequate control of asthma symptoms should be used.

Breast-feeding

Inhaled budesonide is excreted in breast milk, however, when used in therapeutic doses, no effects on the child were noted. It is not known whether formoterol passes into women's breast milk. DuoResp Spiromax can be prescribed to breastfeeding women only if the expected benefit to the mother is greater than any possible risk to the baby.

Fertility

There is no data on the effect on fertility.

Directions for use and doses

For inhalation use.

160/4.5 mcg/dose

Bronchial asthma

Selection of the dose of the drugs included in the drug DuoResp Spiromax occurs individually and depending on the severity of the disease. This must be taken into account not only when starting treatment with combination drugs, but also when changing the maintenance dose of the drug.

Patients should be under constant medical supervision to ensure adequate selection of the dose of DuoResp Spiromax.

DuoResp Spiromax can be used in accordance with various approaches to therapy:

A. DuoResp Spiromax for relief of attacks/symptoms with anti-inflammatory effect (patients with mild bronchial asthma).

B. DuoResp Spiromax as maintenance therapy and for the relief of attacks/symptoms with an anti-inflammatory effect.

Alternatively, DuoResp Spiromax can be used as a fixed dose therapy:

C. DuoResp Spiromax as maintenance therapy (fixed dose).

A. DuoResp Spiromax for relief of attacks/symptoms with anti-inflammatory effect (patients with mild bronchial asthma)

DuoResp Spiromax is taken on demand to relieve symptoms of bronchial asthma as they develop and to prevent bronchoconstriction caused by allergens or exercise (or to prevent symptoms in situations assessed by the patient as capable of triggering an attack of bronchial asthma). Formoterol, the active ingredient in DuoResp Spiromax, provides a rapid onset of action (within 1-3 minutes) with prolonged bronchodilation (at least 12 hours after a single dose) with reversible airway obstruction. The patient must carry DuoResp Spiromax with him at all times to relieve symptoms.

The physician should discuss allergen exposure and the amount of physical activity with the patient and take them into account when recommending the frequency of dosing.

Adults (18 years and older): Patients should take 1 inhalation on demand as symptoms develop and to prevent bronchoconstriction caused by allergens or exercise to control asthma. With a further increase in symptoms within a few minutes, 1 additional inhalation is prescribed, but no more than 6 inhalations to relieve 1 attack.

Usually, more than 8 inhalations per day are not required, but you can increase the number of inhalations to 12 per day for a short time. Patients receiving more than 8 inhalations per day are advised to seek medical help to re-evaluate their condition and review their asthma therapy.

Careful monitoring for dose-related side effects is required in patients using large numbers of on-demand inhalations.

B. DuoResp Spiromax as maintenance therapy and for the relief of attacks/symptoms with anti-inflammatory effect

If maintenance therapy with a combination of an inhaled glucocorticosteroid and a long-acting beta2-adrenergic agonist is required, the patient can take DuoResp Spiromax as maintenance therapy and in addition to relieve attacks/symptoms with anti-inflammatory effects. The patient must carry DuoResp Spiromax with him at all times to relieve symptoms. DuoResp Spiromax as a maintenance therapy and for the relief of attacks/symptoms with anti-inflammatory effect is especially indicated for patients with:

— insufficient control over bronchial asthma and the need for frequent use of drugs to relieve attacks/symptoms; - a history of exacerbations of bronchial asthma that required medical intervention.

The physician should discuss allergen exposure and the amount of physical activity with the patient and take them into account when recommending the frequency of dosing.

Adults (18 years and older): Patients should take 1 inhalation on demand as symptoms develop and to prevent bronchoconstriction caused by allergens or exercise to control asthma. With a further increase in symptoms within a few minutes, 1 additional inhalation is prescribed, but no more than 6 inhalations to relieve 1 attack. Patients also take the recommended maintenance dose - 2 inhalations per day, 1 inhalation in the morning and evening, or 2 inhalations once only in the morning or only in the evening. For some patients, a maintenance dose of 2 inhalations twice daily may be prescribed.

Usually it is not necessary to prescribe more than 8 inhalations per day, but you can increase the number of inhalations to 12 per day for a short time. Patients receiving more than 8 inhalations per day are advised to seek medical attention for re-evaluation and review of maintenance therapy.

Careful monitoring for dose-related side effects is required in patients using large numbers of on-demand inhalations.

S. DuoResp Spiromax as maintenance therapy (fixed dose)

If maintenance therapy with a combination of an inhaled corticosteroid and a long-acting beta2-adrenergic agonist is required, the patient can take DuoResp Spiromax at a fixed daily dose and use a separate short-acting bronchodilator to relieve symptoms. Adults (18 years and older): 1-2 inhalations twice a day. If necessary, the dose can be increased to 4 inhalations twice a day.

The dose should be reduced to the lowest dose that maintains optimal control of asthma symptoms. After achieving optimal control of asthma symptoms when taking the drug twice daily, it is recommended to titrate the dose to the minimum effective dose, up to once daily dosing in cases where, in the opinion of the physician, the patient requires maintenance therapy with a long-acting bronchodilator in combination with inhaled glucocorticosteroid.

In the event that individual patients require a different combination of doses of active substances than in the drug DuoResp Spiromax, beta2-adrenergic agonists and/or glucocorticosteroids should be prescribed in separate inhalers. An increase in the frequency of use of short-acting beta2-agonists is an indicator of deterioration in overall disease control and requires a review of anti-asthma therapy.

COPD

Adults: 2 inhalations twice a day.

Special groups of patients: there is no need for special selection of the drug dose for elderly patients. There is no data on the use of DuoResp Spiromax in patients with renal or hepatic impairment. Since budesonide and formoterol are primarily eliminated by hepatic metabolism, a slower rate of elimination of the drug can be expected in patients with severe cirrhosis.

Mode of application

DuoResp Spiromax is a breath-activated drug, which means that the active substance enters the respiratory tract when the patient inhales it from the mouthpiece.

Patients with moderate to severe asthma are able to develop sufficient inspiratory flow rates to receive a therapeutic dose of DuoResp Spiromax.

To ensure effective treatment, DuoResp Spiromax must be used correctly. Therefore, patients should be advised to carefully read the directions for use of the drug and follow the instructions for medical use.

The use of the drug DuoResp Spiromax includes three stages

.

— Open the mouthpiece cover by turning it down until you hear a click and it opens. — Place the mouthpiece between your teeth, closing your lips around it, without biting the mouthpiece of the inhaler. Take a deep breath from the dispenser. Remove the mouthpiece from the mouth and hold your breath for 10 seconds or longer, as long as is comfortable for the patient. — Carefully exhale and close the dispenser lid.

It is important not to shake the inhaler before use, exhale into the mouthpiece, or hold your breath while preparing to inhale.

After inhalation, it is necessary to rinse the mouth with water.

When using the drug DuoResp Spiromax, the patient may experience a specific taste due to the presence of an excipient - lactose.

Side effect

There was no increase in the incidence of adverse reactions observed during the concomitant administration of the two drugs. The most common adverse reactions associated with taking the drug are such pharmacologically expected undesirable side effects for β2-adrenergic agonists, such as tremor and rapid heartbeat. Symptoms are usually mild and disappear within a few days of starting treatment. During a 3-year clinical study of budesonide in COPD, skin bruising and pneumonia occurred at an incidence of 10% and 6%, respectively, while in the placebo group the incidence was 4% and 3% (p<0.001 and p< 0.01, respectively).

Frequency is determined as follows: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/ 1000), very rare (<1/10000) and frequency unknown (cannot be estimated from available data).

* during treatment with inhaled corticosteroids in patients with COPD.

Systemic effects of inhaled corticosteroids can occur when taking high doses over a long period of 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.

Overdose

Symptoms of formoterol overdose: tremor, headache, rapid heartbeat. In some cases, the development of tachycardia, hyperglycemia, hypokalemia, prolongation of the QT interval, arrhythmia, nausea and vomiting was reported.

In case of acute overdose of budesonide, even in significant doses, no clinically significant effects are expected. With chronic use of excessive doses, systemic effects of GCS, such as hypercortisolism and suppression of adrenal function, may occur.

If it is necessary to discontinue the drug DuoResp Spiromax due to an overdose of formoterol, which is part of the combination drug, the issue of prescribing inhaled GCS should be considered.

Treatment: supportive and symptomatic.

Interaction with other drugs

Taking ketoconazole 200 mg once a day increases the plasma concentration of oral budesonide (single dose 3 mg) when administered together by an average of 6 times. When ketoconazole was prescribed 12 hours after taking budesonide, the plasma concentration of the latter increased by an average of 3 times. There is no information about such an interaction with inhaled budesonide, but a noticeable increase in the concentration of the drug in the blood plasma should be expected. Since there are no data for dose recommendations, the above combination of drugs should be avoided. If possible, the time interval between the administration of ketoconazole and budesonide should be increased as much as possible. A dose reduction of budesonide should also be considered. Other potent CYP3A4 inhibitors are also likely to significantly increase budesonide plasma concentrations.

β2-adrenergic receptor blockers may reduce the effect of formoterol. The combination of formoterol + budesonide should not be prescribed 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) and 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 β2-agonists.

The simultaneous use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine, may cause an increase in blood pressure. There is an increased risk of developing arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbon preparations.

With simultaneous use of the combination of formoterol + budesonide and other β-adrenergic drugs, the side effects of formoterol may be increased.

As a result of the use of β2-agonists, hypokalemia may occur, which may be exacerbated by concomitant treatment with xanthine derivatives, corticosteroids or diuretics. Hypokalemia may increase the susceptibility to the development of arrhythmias in patients taking cardiac glycosides.

There was no interaction between budesonide and formoterol with other drugs used to treat bronchial asthma.

special instructions

Dosage Directions

If the symptoms of bronchial asthma are controlled, you can gradually reduce the dose of DuoResp Spiromax. It is important to constantly monitor the condition of patients. The lowest effective dose of DuoResp Spiromax should be prescribed (see section “Dosage and Administration”).

Patients are advised to always carry emergency medications or DuoResp Spiromax (for patients with bronchial asthma using DuoResp Spiromax for relief of attacks/symptoms with anti-inflammatory action - therapy A or B), or short-acting beta2-agonists (for all patients using DuoResp Spiromax for maintenance therapy only - therapy C).

When using the drug DuoResp Spiromax as maintenance therapy, the patient should be drawn to the need to regularly take a maintenance dose of the drug in accordance with the selected therapy, even in cases where there are no symptoms of the disease.

It is recommended to instruct the patient to rinse the mouth with water after inhaling maintenance doses in order to prevent the risk of developing candidiasis of the oral and pharyngeal mucosa. It is also necessary to rinse your mouth with water after inhalation on demand in case of development of candidiasis of the oral mucosa and pharynx.

It is recommended to gradually reduce the maintenance dose of the drug before stopping treatment and it is not recommended to abruptly discontinue treatment. Inhaled glucocorticosteroids should not be completely discontinued, except in cases where temporary withdrawal is necessary to confirm the diagnosis of bronchial asthma.

Increased symptoms of the disease

During therapy with DuoResp Spiromax, exacerbations and the development of serious adverse events associated with bronchial asthma may occur. Patients should continue treatment but seek medical attention if asthma symptoms are not controlled or if symptoms worsen after starting therapy.

If therapy is insufficiently effective or the maximum recommended doses of DuoResp Spiromax are exceeded, it is necessary to reconsider treatment tactics. Sudden and progressive deterioration in control of symptoms of asthma or COPD is a potentially life-threatening condition and requires urgent medical attention. In this situation, you should consider increasing the dose of glucocorticosteroids, for example, prescribing a course of oral glucocorticosteroids, or treatment with antibiotics in case of infection. In case of severe exacerbation, monotherapy with a combination of an inhaled glucocorticosteroid and a long-acting beta2-adrenergic agonist is not enough.

Transfer from oral therapy

If there is reason to believe that adrenal function has been impaired due to previous systemic glucocorticosteroid therapy, precautions should be taken when transferring patients to treatment with DuoResp Spiromax.

The benefits of inhaled budesonide therapy generally minimize the need for oral corticosteroids, but patients who discontinue oral corticosteroid therapy may experience long-term adrenal insufficiency. Patients who have previously required acute high-dose corticosteroids or have received long-term treatment with high-dose inhaled corticosteroids may also be at risk. It is necessary to provide additional administration of glucocorticosteroids during periods of stress or surgery.

Excipients

DuoResp Spiromax contains lactose (< 1 mg/inhalation). Typically this amount does not cause problems in patients with lactose intolerance.

Precautions for specific diseases

Precautions should be taken when treating patients with a prolonged QTc interval. Taking formoterol may cause a prolongation of the QTc interval.

When beta2-agonists are used together with drugs that can cause or enhance the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, the hypokalemic effect of beta2-agonists may be enhanced. Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve attacks during exacerbation of severe bronchial asthma, since 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 monitor serum potassium levels.

During treatment, blood glucose concentrations should be monitored in patients with diabetes mellitus.

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

Systemic action

Systemic effects may occur when taking any inhaled glucocorticosteroids, especially when taking high doses of drugs over a long period of time. Systemic effects are less likely to occur with inhaled therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, 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. Studies of long-term use of inhaled budesonide in children at an average daily dose of 400 mcg (metered dose) or adults at a daily dose of 800 mcg (metered dose) did not show a significant effect on bone mineral density. There is no data regarding the effect of high doses of DuoResp Spiromax on bone mineral density.

Paradoxical bronchospasm

As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after taking a dose of the drug. In this regard, therapy with DuoResp Spiromax should be discontinued, treatment tactics should be reconsidered and, if necessary, alternative therapy should be prescribed.

Population of patients with COPD

Data from clinical studies of DuoResp Spiromax in patients with COPD with pre-bronchodilator FB1 > 50% of predicted and post-bronchodilator FB1 < 70% of predicted are not available (see section “Pharmacodynamics”).

Clinical studies and meta-analyses have shown that the use of inhaled corticosteroids for COPD may lead to an increased risk of pneumonia. However, the absolute risk with budesonide is small. A meta-analysis of 11 double-blind studies involving 10,570 patients with COPD did not demonstrate a statistically significant increase in the risk of pneumonia in patients receiving budesonide (including in combination with formoterol) compared with patients receiving therapy without budesonide (placebo or formoterol). The incidence of the serious adverse event of pneumonia was 1.9% per year with budesonide-containing therapy and 1.5% per year with budesonide-free therapy. The pooled hazard ratio comparing therapy containing budesonide to therapy without budesonide was 1.15 (95% confidence interval (CI): 0.83, 1.57). The pooled hazard ratio comparing budesonide/formoterol with formoterol or placebo was 1.00 (95% CI: 0.69, 1.44). The cause-and-effect relationship between the development of pneumonia and the use of drugs containing budesonide has not been established.

Impact on the ability to drive vehicles and machinery

The drug DuoResp Spiromax may affect the ability to drive vehicles and machinery if side effects occur, so care must be taken when driving vehicles and machinery.

Release form

Powder for inhalation, dosed, 160/4.5 mcg/dose, 320/9 mcg/dose.

60 doses (for a dosage of 320/9 mcg/dose) or 120 doses (for a dosage of 160/4.5 mcg/dose) in a white plastic inhaler with a translucent red cap. There is a label on the inhaler. The inhaler is placed in foil. 1 or 3 inhalers along with instructions for use in a cardboard box with tamper evident.

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Best before date

3 years.

The shelf life of the drug after opening the foil wrapper is 6 months.

Do not use after the expiration date.

Vacation conditions

Dispensed by prescription.

special instructions

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

DuoResp Spiromax is not used for the initial selection of therapy in the first stages of treatment of bronchial asthma.

Taking formoterol may cause QT prolongation.

An increase in the frequency of taking bronchodilators as emergency medications indicates a worsening of the underlying disease and serves as a basis for revising the treatment tactics for bronchial asthma. Sudden and progressive deterioration in control of symptoms of asthma or COPD is a potentially life-threatening condition and requires urgent medical attention. In this situation, you should consider increasing the dose of GCS or adding systemic anti-inflammatory therapy, for example, a course of oral GCS or antibiotic treatment in case of infection. Patients are advised to carry emergency medications (short-acting beta2-agonists) with them at all times.

The patient's attention should be drawn to the need to regularly take DuoResp Spiromax in accordance with the selected dose, even in cases where there are no symptoms of the disease.

Treatment with DuoResp Spiromax should not be started during periods of exacerbation or significant worsening of bronchial asthma.

As with any other inhaled therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after taking a dose of the drug. In this regard, therapy with DuoResp Spiromax should be discontinued, treatment tactics should be reconsidered and, if necessary, alternative therapy should be prescribed.

Duoresp Spiromax instructions for use

Clinical and pharmacological group Drug with anti-inflammatory and bronchodilator effects Release form, composition and packaging Dosed powder for inhalation of white or almost white color, without visible lumps and inclusions; the dosing indicator window should show No. 120.1 delivered dose of budesonide (micronized) 160 mcg formoterol fumarate dihydrate (micronized) 4.5 mcg Excipients: lactose monohydrate - 5 mg*. 120 doses - plastic inhalers (1), placed in foil - cardboard packs. 120 doses - plastic inhalers (3), placed in foil - cardboard packs.

Powder for inhalation, dosed, white or almost white, without visible lumps or inclusions; the dosing indicator window should show No. 60.1 delivered dose of budesonide (micronized) 320 mcg formoterol fumarate dihydrate (micronized) 9 mcg Excipients: lactose monohydrate - 10 mg*. 60 doses - plastic inhalers (1), placed in foil - cardboard packs. 60 doses - plastic inhalers (3), placed in foil - cardboard packs. * the target amount in the delivered dose is indicated (is approximate).

Indications : bronchial asthma, insufficiently controlled by taking inhaled corticosteroids and short-acting beta2-agonists or adequately controlled by inhaled corticosteroids and long-acting beta2-agonists; - COPD - symptomatic therapy in patients with severe COPD (FEV1 <50% of the estimated calculated level) and with a history of repeated exacerbations, who have severe symptoms of the disease, despite therapy with long-acting bronchodilators.

Contraindications : hypersensitivity to budesonide, formoterol or inhaled lactose; - children and adolescents up to 18 years of age. With caution: pulmonary tuberculosis (active or inactive form), fungal, viral or bacterial respiratory infections, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any location or other severe cardiovascular diseases (CHD, tachyarrhythmia or severe heart failure), prolongation of the QT interval (taking formoterol may cause prolongation of the QTc interval), lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Dosage Bronchial asthma The drug DuoResp Spiromax is not intended for the initial treatment of intermittent and mild persistent bronchial asthma. Selection of the dose of the drugs included in the drug DuoResp Spiromax occurs individually and depending on the severity of the disease. This must be taken into account not only when starting treatment with combination drugs, but also when changing the maintenance dose of the drug. In the event that individual patients require a different combination of doses of active components than in the drug DuoResp Spiromax, beta2-agonists and/or corticosteroids should be prescribed in separate inhalers. Patients should visit their doctor regularly to monitor the optimal dose of DuoResp Spiromax. The dose should be reduced to the lowest dose that maintains optimal control of asthma symptoms. After achieving optimal control of bronchial asthma when taking the drug 2 times a day, it is recommended to titrate the dose to the minimum effective, up to taking the drug 1 time a day, in cases where, in the opinion of the doctor, the patient requires maintenance therapy in combination with a long-acting bronchodilator . Adults (18 years and older) DuoResp Spiromax 160/4.5 mcg/dose as maintenance therapy 1-2 inhalations 2 times a day. If necessary, the dose can be increased to 4 inhalations 2 times a day. The patient must always have with him a separate inhaler with a short-acting beta2-adrenergic agonist to relieve attacks. An increase in the frequency of use of short-acting beta2-agonists is an indicator of deterioration in overall disease control and requires a review of anti-asthmatic therapy. The drug DuoResp Spiromax 160/4.5 mcg/dose as maintenance therapy and for the relief of attacks DuoResp Spiromax can be prescribed both as continuous maintenance therapy and as on-demand therapy when attacks occur. As a maintenance therapy and for the relief of attacks, it is especially indicated for patients with: - insufficient control over bronchial asthma and the need for frequent use of drugs to relieve attacks; - a history of exacerbations of bronchial asthma that required medical intervention. Careful monitoring of dose-related side effects is required in patients using large numbers of inhalations to relieve attacks. The recommended dose for maintenance therapy is 2 inhalations/day: 1 inhalation in the morning and evening, or 2 inhalations 1 time/day only in the morning or only in the evening. For some patients, a maintenance dose of DuoResp Spiromax 160/4.5 mcg/dose may be prescribed - 2 inhalations 2 times a day. If symptoms occur, 1 additional inhalation is necessary. With a further increase in symptoms within a few minutes, 1 additional inhalation is prescribed, but no more than 6 inhalations to relieve 1 attack. Usually it is not necessary to prescribe more than 8 inhalations per day, but you can increase the number of inhalations to 12 per day for a short time. Patients receiving more than 8 inhalations per day are advised to seek medical help to review therapy. The drug DuoResp Spiromax 320/9 mcg/dose Prescribe 1 inhalation 2 times a day. If necessary, the dose can be increased to 2 inhalations 2 times a day. After achieving optimal control of the symptoms of bronchial asthma while taking the drug 2 times a day, it is possible to reduce the dose to the lowest effective dose, up to 1 time a day. COPD Adults (18 years and older) DuoResp Spiromax 160/4.5 mcg/dose 2 inhalations 2 times/day. DuoResp Spiromax 320/9 mcg/dose 1 inhalation 2 times/day.

Special groups of patients There is no need for special selection of the drug dose for elderly patients. There is no data on the use of DuoResp Spiromax in patients with renal or hepatic impairment. Because Budesonide and formoterol are eliminated primarily by the kidneys, with the participation of hepatic metabolism; in patients with severe cirrhosis, a slower rate of elimination of the drug can be expected.

Rules for using the drug DuoResp Spiromax is a breath-activated drug, which means that the active substance enters the respiratory tract when the patient inhales it from the mouthpiece. Patients with moderate to severe asthma are able to develop sufficient inspiratory flow rates to receive a therapeutic dose of DuoResp Spiromax. To ensure effective treatment, DuoResp Spiromax should be used correctly. Therefore, patients should be advised to carefully read the directions for use of the drug and follow the instructions for medical use.

The use of DuoResp Spiromax includes three stages. 1. Open the mouthpiece cover by turning it down until you hear a click and it opens. 2. Place the mouthpiece between your teeth, closing your lips around it, without biting the mouthpiece of the inhaler. Take a deep breath from the dispenser. Remove the mouthpiece from the mouth and hold your breath for 10 seconds or longer, as long as is comfortable for the patient. 3. Carefully exhale the air and close the dispenser lid. It is important not to shake the inhaler before use, exhale into the mouthpiece, or hold your breath while preparing to inhale. After inhalation, it is necessary to rinse the mouth with water. When using the drug DuoResp Spiromax, the patient may experience a specific taste due to the presence of an excipient - lactose.

Side effects During the co-administration of budesonide and fenoterol, there was no increase in the incidence of adverse reactions. The most common adverse reactions associated with taking the drug are such pharmacologically expected undesirable side effects for beta2-agonists, such as tremor and rapid heartbeat. Symptoms are usually mild and disappear within a few days of starting treatment. During a 3-year clinical trial of budesonide in COPD, skin bruising and pneumonia occurred at rates of 10% and 6%, respectively, compared with 4% and 3% in the placebo group (p<0.001 and p<0.01). respectively). Determination of the frequency of adverse reactions: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10,000, <1 /1000), very rare (<1/10,000) and unknown (cannot be estimated from available data). Frequency Adverse reactions From the immune system Rarely immediate and delayed hypersensitivity reactions (exanthema, urticaria, itching, dermatitis, angioedema and anaphylactic reaction) From the endocrine system Very rarely Cushing's syndrome adrenal suppression growth retardation decreased bone mineral density Metabolism Rarely hypokalemia Very rare hypoglycemia signs or symptoms of systemic glucocorticoid effects (including hypoadrenal gland dysfunction) Nervous system disorders Common headache tremor Uncommon dizziness Very rare taste disturbances Psychiatric disorders Uncommon agitation psychomotor agitation anxiety sleep disturbances Very rare depression behavioral disorders Visual disorders Very rare cataract glaucoma From the cardiovascular system Often palpitations Uncommon tachycardia Rarely arrhythmia (for example, atrial fibrillation, supraventricular tachycardia, extrasystole) Very rarely angina pectoris prolongation of the QT interval blood pressure fluctuations From the respiratory system Often candidiasis of the oral mucosa and pharynx pharyngeal irritation cough hoarseness Rarely bronchospasm Very rarely paradoxical bronchospasm From the digestive system Uncommon nausea From the skin and subcutaneous tissues Uncommon bruising From the musculoskeletal system Uncommon muscle cramps Systemic effects of inhaled corticosteroids can occur when taken in high doses for a long time. The use of beta2-agonists can lead to an increase in the blood levels of insulin, free fatty acids, glycerol and ketone derivatives.

Overdose Symptoms: in case of formoterol overdose - tremor, headache, rapid heartbeat. In isolated cases, the development of tachycardia, hyperglycemia, hypokalemia, prolongation of the QTc interval, arrhythmia, nausea and vomiting was reported. In case of acute overdose of budesonide, even in significant doses, no clinically significant effects are expected. With chronic use of excessive doses, systemic effects of GCS, such as hypercortisolism and suppression of adrenal function, may occur. Treatment: supportive and symptomatic therapy is provided. If it is necessary to discontinue the drug DuoResp Spiromax due to an overdose of formoterol, the issue of prescribing an appropriate GCS should be considered. Formoterol at a dose of 90 mcg over 3 hours is safe for patients with acute bronchial obstruction.

Drug interactions Taking ketoconazole at a dose of 200 mg 1 time/day increases the plasma concentration of budesonide when administered orally (single dose 3 mg) when administered together by an average of 6 times. When ketoconazole was prescribed 12 hours after taking budesonide, the plasma concentration of the latter increased, on average, 3 times. There is no information about such an interaction with budesonide when administered inhaled, but a noticeable increase in the concentration of the drug in the blood plasma should be expected. Because There are no data for dose selection recommendations; the above combination of drugs should be avoided. If possible, the time interval between the administration of ketoconazole and budesonide should be increased as much as possible. A dose reduction of budesonide should also be considered. Other strong CYP3A4 inhibitors are also likely to significantly increase budesonide plasma concentrations. β2-adrenergic receptor blockers can reduce the intensity of the action of formoterol. The combination of formoterol + budesonide should not be prescribed 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 in blood pressure. There is an increased risk of developing arrhythmias in patients undergoing general anesthesia with halogenated hydrocarbon preparations. With simultaneous use of the combination of formoterol + budesonide 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 exacerbated by concomitant treatment with xanthine derivatives, corticosteroids or diuretics. Hypokalemia may increase the susceptibility to the development of arrhythmias in patients taking cardiac glycosides. There was no interaction between budesonide and formoterol with other drugs used to treat bronchial asthma.

Special instructions Before stopping treatment, it is recommended to gradually reduce the dose of the drug. It is not recommended to abruptly cancel treatment. DuoResp Spiromax is not used for the initial selection of therapy in the first stages of treatment of bronchial asthma. Taking formoterol may cause QT prolongation. An increase in the frequency of taking bronchodilators as emergency medications indicates a worsening of the underlying disease and serves as a basis for revising the treatment tactics for bronchial asthma. Sudden and progressive deterioration in control of symptoms of asthma or COPD is a potentially life-threatening condition and requires urgent medical attention. In this situation, you should consider increasing the dose of GCS or adding systemic anti-inflammatory therapy, for example, a course of oral GCS or antibiotic treatment in case of infection. Patients are advised to carry emergency medications (short-acting beta2-agonists) with them at all times. The patient's attention should be drawn to the need to regularly take DuoResp Spiromax in accordance with the selected dose, even in cases where there are no symptoms of the disease. Treatment with DuoResp Spiromax should not be started during periods of exacerbation or significant worsening of bronchial asthma. As with any other inhaled therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after taking a dose of the drug. In this regard, therapy with DuoResp Spiromax should be discontinued, treatment tactics should be reconsidered and, if necessary, alternative therapy should be prescribed. Systemic effects may occur when taking any inhaled corticosteroids, especially when taking drugs in high doses over a long period of time. Systemic effects are less likely to occur with inhalation therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, decreased bone mineral density, cataracts, and glaucoma. Based on the limited data from studies of long-term corticosteroid use, it can be assumed that most children and adolescents receiving inhaled budesonide therapy will eventually achieve normal adult growth rates. However, slight (approximately 1 cm), short-term growth retardation has been reported, mainly in the first year of treatment. 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 the presence of risk factors for osteoporosis. Studies of long-term use of inhaled budesonide in children at an average daily dose of 400 mcg (metered dose) or adults at a daily dose of 800 mcg (metered dose) did not show a significant effect on bone mineral density. There is no data regarding the effect of high doses of DuoResp Spiromax on bone mineral density. If there is reason to believe that adrenal function has been impaired due to previous systemic GCS therapy, precautions should be taken when transferring patients to treatment with DuoResp Spiromax. The benefits of inhaled budesonide therapy generally minimize the need for oral steroids; however, patients who discontinue oral corticosteroid therapy may experience long-term adrenal insufficiency. Patients who in the past required acute use of high doses of corticosteroids or received long-term treatment with high-dose inhaled corticosteroids may also be at this risk. It is necessary to provide additional administration of GCS during periods of stress or surgery. It is recommended to instruct the patient to rinse the mouth with water after inhalation in order to prevent the development of candidiasis of the oral mucosa. Precautions should be taken when treating patients with a prolonged QTc interval. Taking formoterol may cause a prolongation of the QTc interval. The need for the use and dose of inhaled GCS should be reconsidered in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system. When beta2-agonists are co-administered with drugs that can cause or enhance the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, the hypokalemic effect of beta2-agonists may be enhanced. Special precautions should be taken in patients with unstable bronchial asthma using short-acting bronchodilators to relieve attacks during 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 monitor serum potassium levels. During treatment, blood glucose concentrations should be monitored in patients with diabetes mellitus. Effect on the ability to drive vehicles and operate machinery The drug DuoResp Spiromax does not affect the ability to drive vehicles and operate machinery. May have a minor effect if side effects occur. Caution must be exercised when operating vehicles and machinery due to the possibility of side effects. Pregnancy and lactation There are no clinical data on the use of DuoResp Spiromax or the combined use of formoterol and budesonide during pregnancy. During pregnancy, DuoResp Spiromax should be used only in cases where the benefit of treatment with the drug outweighs the potential risk to the fetus. Budesonide should be used at the minimum effective dose necessary to maintain adequate control of asthma symptoms. Inhaled budesonide is excreted in breast milk, however, when used in therapeutic doses, no effects on the child were noted. It is not known whether formoterol is excreted into breast milk in women. DuoResp Spiromax can be prescribed to breastfeeding women only if the expected benefit to the mother outweighs any possible risk to the baby. In case of renal impairment There is no data on the use of DuoResp Spiromax in patients with renal failure. Because Budesonide and formoterol are excreted mainly by the kidneys, with the participation of hepatic metabolism, then in patients with severe liver cirrhosis, a slower rate of elimination of the drug can be expected. In case of impaired liver function, there is no data on the use of the drug DuoResp Spiromax in patients with liver failure. Because Budesonide and formoterol are eliminated primarily by the kidneys, with the participation of hepatic metabolism, then in patients with severe cirrhosis of the liver a slower rate of elimination of the drug can be expected Diagnoses Status asthmaticus Bronchitis Cough Cystic fibrosis

Use in the elderly There is no need for special selection of the drug dose for elderly patients.

Conditions for dispensing from pharmacies The drug is dispensed with a prescription.

Conditions and periods of storage The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life: 2 years. The shelf life of the drug after opening the foil wrapper is 6 months.