Composition, form of production and packaging
The powder for inhalation is dosed white or almost white, without visible lumps and inclusions; the metering indicator window should show No. 120.
1 delivered dose
budesonide (micronized) 160 Ојg
formoterol fumarate dihydrate (micronized) 4.5 Ојg
Excipients: lactose monohydrate - 5 mg *.
120 doses - plastic inhalers (1), placed in foil - packs of cardboard.
120 doses - plastic inhalers (3), placed in foil - packs of cardboard.
The powder for inhalation is dosed white or almost white, without visible lumps and inclusions; the metering indicator window should show No. 60.
1 delivered dose
budesonide (micronized) 320 Ојg
formoterol fumarate dihydrate (micronized) 9 Ојg
Excipients: lactose monohydrate - 10 mg *.
60 doses - plastic inhalers (1), placed in foil - packs of cardboard.
60 doses - plastic inhalers (3), placed in foil - packs cardboard.
* The target quantity in the delivered dose is indicated (it is approximate).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
Combined bronchodilator. DuoResp Spiromax contains formoterol and budesonide, which 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 budesonide and formoterol make it possible to use their combination at the same time as maintenance therapy and for relief of seizures, or as a supporting therapy for bronchial asthma.
Budesonide - GCS, which after inhalation has a rapid (for 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. With the appointment of inhaled budesonide, there is a lower incidence of serious adverse effects than with systemic GCS. Reduces the severity of the bronchial mucosa edema, mucus production, sputum formation and airway hyperreactivity. The exact mechanism of anti-inflammatory action of GCS is unknown.
Formoterol is a selective agonist? 2- adrenoreceptors, which after inhalation causes a rapid and prolonged relaxation of the smooth muscles of the bronchi in patients with reversible airway obstruction. Broncholytic dose-dependent action occurs rapidly, within 1-3 min after inhalation and remains for at least 12 h after taking a single dose.
Budesonide + Formoterol
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 action of a combination of mono preparations of budesonide and formoterol and exceeds the effect of a single budesonide. In all cases, beta 2 -adrenostimulator of short action was used to stop seizures. There was no decrease in the anti-asthmatic effect with time. The drug is well tolerated.
Clinical efficacy as maintenance therapy and for relief of seizures (only for a dosage of 160 / 4.5).
In a follow-up of 4,447 patients receiving a combination of budesonide / formoterol as maintenance therapy and for relieving seizures for 6 to 12 months, there was a statistically and clinically significant decrease in the number of severe exacerbations, an increase in the time to the onset of the first exacerbation compared with the combination budesonide / formoterol or with budesonide as maintenance therapy and beta 2 -adrenostimulator for relief of attacks. There was also effective control over the symptoms of the disease, pulmonary function and a reduction in the frequency of administration of inhalations for relief of attacks. There was no development of tolerance to prescribed therapy. In patients who applied for medical assistance in connection with the development of an acute attack of bronchial asthma, after the inhalation of budesonide / formoterol, the relief of symptoms (removal of bronchospasm) occurred as quickly and effectively as after administration of salbutamol and formoterol.
Chronic obstructive pulmonary disease
In patients with severe COPD, a significant reduction in the frequency of exacerbations of the disease was observed compared with patients receiving only formoterol or placebo (average frequency of exacerbations 1.4 compared with 1.8-1.9 in the placebo / formoterol group) when taking DuoResp Spiromax. There was no difference between taking DuoResp Spiromax and formoterol with the FEV1 index.
The drug DuoResp Spiromax is bioequivalent to the corresponding mono preparations with respect to the systemic action of budesonide and formoterol. Despite this, there was a slight increase in cortisol suppression after taking DuoResp Spiromax as compared with mono preparations. This difference does not affect clinical safety.There is no evidence of pharmacokinetic interaction between budesonide and formoterol.
Pharmacokinetic parameters for the relevant substances are comparable after administration of budesonide and formoterol in the form of monopreparations and as part of DuoResp Spiromax. For budesonide with the introduction of the combined preparation AUC is somewhat more, the absorption of the drug is faster and the Cmax value in the blood plasma is higher.
For formoterol, when administered in a combination preparation, Cmax in blood plasma coincides with that for a mono drug.
Inhaled budesonide is rapidly absorbed and reaches C max in plasma 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, trapped in the lungs after inhalation, does not differ from those in adult patients (the final concentration of the drug in the blood plasma was not determined).
Inhaled formoterol is rapidly absorbed and reaches C max in blood plasma 10 minutes after the inhalation. The average dose of formoterol, trapped in the lungs after inhalation, is 28-49% of the delivered dose. Systemic bioavailability is about 61% of the delivered dose.
Binding to plasma proteins formoterol is 50%, budesonide - 90%. V d of formoterol is about 4 l / kg, budesonide is 3 l / kg.
Metabolism and excretion
Formoterol is inactivated by conjugation (active O-demethylated metabolites are formed, mainly in the form of inactivated conjugates). Budesonide undergoes intensive biotransformation (about 90%) with the first "passage through the liver" with the formation of metabolites with low glucocorticoid activity. Glucocorticoid activity of the main metabolites of 6 -? - hydroxybudesonide and 16 -? - hydroxyprednisolone does not exceed 1% of the analogous activity of budesonide. There is no evidence for the interaction of metabolites or substitution reactions between budesonide and formoterol.
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 system clearance (approximately 1.4 l / min); T 1/2 of the drug is an average of 17 hours.
Budesonide is metabolized predominantly with the participation of the enzyme CYP3A4. Metabolites of budesonide are excreted in the urine in unchanged form or in the form of conjugates. In urine, only a small amount of unmodified budesonide is found. Budesonide has a high system clearance (about 1.2 l / min).
Pharmacokinetics in special clinical cases
The pharmacokinetics of formoterol in children and in patients with renal insufficiency has not been studied.
The concentration of budesonide and formoterol in blood plasma can be increased in patients with liver disease.
- bronchial asthma, insufficiently controlled by ingestion of inhaled glucocorticosteroids and beta 2 -adrenostimulators of short-acting or adequately controlled by inhaled GCS and beta 2 -adrenostimulators of long-acting;
- COPD - symptomatic therapy in patients with severe COPD (FEV1 <50% of the estimated calculated level) and with repeated exacerbations in the anamnesis, which have severe symptoms of the disease, despite the therapy with long-acting bronchodilators.
The drug DuoResp Spiromax is not intended for the initial treatment of bronchial asthma of intermittent and easy persistent flow. Selection of the dose of the preparations that make up the preparation DuoResp Spiromax takes place individually and depending on the severity of the disease. This need to be taken into account not only at the beginning of treatment with combined preparations, but also with a change in the maintenance dose of the drug.
In the event that individual combinations require a different combination of active ingredient doses than DuoResp Spiromax, beta2-adrenostimulants and / or GCS should be given in separate inhalers.
Patients should visit the doctor regularly to monitor the optimal dose of DuoResp Spiromax. The dose should be reduced to the lowest, against which the optimal control of symptoms of bronchial asthma remains. After achieving optimal control of bronchial asthma when taking the drug 2 times / day, it is recommended to titrate the dose to the minimum effective, up to taking the drug 1 time / day, in those cases when, according to the doctor, the patient needs maintenance therapy in combination with a long-acting bronchodilator .
Adults (18 years and over)
The drug DuoResp Spiromax 160 / 4.5 mcg / dose as maintenance therapy
1-2 inhalations 2 times / day. If necessary, it is possible to increase the dose to 4 inhalations 2 times / day. The patient should always have a separate inhaler with a beta2 -adrenostimulator of short action for relief of attacks. An increase in the frequency of beta 2 -adrenergic stimulants of short action is an indicator of worsening of general control over the disease and requires revision of anti-asthmatic therapy.
The drug DuoResp Spiromax 160 / 4.5 mcg / dose as maintenance therapy and for relief of attacks
DuoResp Spiromax can be prescribed both as a permanent maintenance therapy, and as a therapy on demand when seizures occur. As maintenance therapy and for relief of seizures, it is especially indicated for patients with:
-Inadequate control of bronchial asthma and the need for frequent use of drugs to stop seizures;
- the presence in an anamnesis of exacerbations of bronchial asthma, requiring medical intervention.
It requires careful monitoring of dose-dependent side effects in patients who use a large number of inhalations to stop seizures.
The recommended dose for maintenance therapy is 2 inhalations / day: 1 inhalation in the morning and in the 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 Ојg / dose - 2 inhalations 2 times / day may be prescribed. If symptoms occur, the appointment of 1 additional inhalation is necessary. With a further increase in symptoms within a few minutes, another 1 additional inhalation is prescribed, but no more than 6 inhalations for stopping 1 attack.
Usually, no more than 8 inhalations per day are required, but you can increase the number of inhalations to 12 per day for a short time. Patients who receive more than 8 inhalations per day are advised to seek medical help for a review of therapy.
The drug DuoResp Spiromax 320/9 mcg / dose
Assign 1 inhalation 2 times / day. If necessary, it is possible to increase the dose to 2 inhalations 2 times / day.
After achieving the optimal control of the symptoms of bronchial asthma against the background of taking the drug 2 times / day, it is possible to reduce the dose to the lowest effective, up to a dose of 1 time / day.
Adults (18 years and over)
DuoResp Spiromax 160 / 4.5 mcg / dose 2 inhalations 2 times / day.
DuoResp Spiromax 320/9 mcg / dose 1 inhalation 2 times / day.
Special patient groups
There is no need for a special dose selection for elderly patients .
There are no data on the use of DuoResp Spiromax in patients with renal or hepatic insufficiency . Because budesonide and formoterol are excreted mainly by the kidneys, with the participation of hepatic metabolism, in patients with severe cirrhosis of the liver , a slowing down of the drug release rate can be expected.
DuoResp Spiromax is a drug activated by inhalation, which means the entry of the active substance into the respiratory tract, when the patient inhales it from the mouthpiece.
Patients with moderate to severe asthma are able to develop a sufficient flow rate on inhalation 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 instructions for use and follow the instructions for medical use.
The use of DuoResp Spiromax consists of three steps.
1. Open the lid of the mouthpiece by turning it down until it clicks and it does not open.
2. Place the mouthpiece between the teeth, closing the lips around it, without biting the mouthpiece of the inhaler. Deeply inhale from the dispenser. Get the mouthpiece from the mouth and hold your breath for 10 seconds or longer - as much as it is comfortable for the patient.
3. Carefully exhale the air and close the dispenser cover.
It is important not to shake the inhaler before use, do not exhale into the mouthpiece and do not hold your breath, preparing for inhalation.
After inhalation, rinse the oral cavity with water.
When using the drug DuoResp Spiromax, the patient can feel a specific taste due to the presence of an auxiliary substance - lactose.
Against the background of co-administration of budesonide and fenoterol, there was no increase in incidence of adverse reactions. The most common adverse reactions associated with taking the drug are pharmacologically expected for beta 2 -adrenomimetics unwanted side effects, such as tremor and heart palpitations.Symptoms usually have a moderate degree of severity and go away a few days after the start of treatment. During a 3-year clinical trial of budesonide in COPD, bruising on the skin and pneumonia occurred at a frequency of 10% and 6%, respectively, while in the placebo group it was 4% and 3% (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 rarely (<1/10 000) and is unknown (can not be estimated from available data).
Frequency Adverse Reactions
From the immune system
Rarely immediate and delayed hypersensitivity reactions (exanthema, urticaria, pruritus, dermatitis angioedema and anaphylactic reaction)
From the endocrine system
Very rarely Cushing's syndrome adrenal suppression slowing down the growth of a decrease in bone mineral density
From the side of metabolism
Very rarely hypoglycemia signs or symptoms of systemic glucocorticoid effects (including adrenal hypofunction)
From the nervous system
Often headache tremor
Very rarely a taste disorder
From the side of the psyche
Infrequent agitation of psychomotor agitation disturbance of sleep disturbance
Very rarely depression behavior disorders
From the side of the organ of vision
Very rarely cataract glaucoma
From the side of the cardiovascular system
Rarely arrhythmia (eg, atrial fibrillation, supraventricular tachycardia, extrasystole)
Very rarely, angina prolongation of the QT interval of blood pressure fluctuation
From the respiratory system
Often candidiasis of the oral mucosa and pharynx irritation of the pharynx cough hoarseness
Very rarely paradoxical bronchospasm
From the digestive system
Not often nausea
From the skin and subcutaneous tissues
From the musculoskeletal system
Infrequent muscle cramps
Systemic exposure to inhaled glucocorticosteroids may occur with high doses for a long time. The use of beta 2 -adrenostimulators can lead to an increase in the blood levels of insulin, free fatty acids, glycerol and ketone derivatives.
- hypersensitivity to budesonide, formoterol or inhaled lactose;
- Children and adolescence under 18 years.
With caution: pulmonary tuberculosis (active or inactive form), fungal, viral or bacterial infections of the respiratory system, thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortic stenosis, severe arterial hypertension, aneurysm of any site or other severe cardiovascular diseases (Р�Р‘РЎ, С‚Р°С…РёР°СЂРёС‚РјРёСЏ РёР»Рё СЃРµСЂРґРµС‡РЅР°СЏ РЅРµРґРѕСЃС‚Р°С‚РѕС‡РЅРѕСЃС‚СЊ С‚СЏР¶РµР»РѕР№ СЃС‚РµРїРµРЅРё), СѓРґР»РёРЅРµРЅРёРµ РёРЅС‚РµСЂРІР°Р»Р° QT (РїСЂРёРµРј С„РѕСЂРјРѕС‚РµСЂРѕР»Р° РјРѕР¶РµС‚ РІС‹Р·РІР°С‚СЊ СѓРґР»РёРЅРµРЅРёРµ РёРЅС‚РµСЂРІР°Р»Р° QT c ), РЅРµРїРµСЂРµРЅРѕСЃРёРјРѕ st lactose, lactase deficiency or glucose-galactose malabsorption.
PREGNANCY AND LACTATION
No clinical data on the use of the drug DuoResp Spiromaks or formoterol and budesonide sharing during pregnancy.
When pregnancy DuoResp Spiromaks should be used only in cases where the benefits of drug treatment outweighs the potential risk to the fetus. Budesonide should be used in the lowest effective dose needed to maintain adequate control of asthma symptoms.
Inhaled budesonide is excreted in breast milk, but in the application were observed at therapeutic doses, effects on the child. It is not known whether formoterol is excreted in breast milk in women. DuoResp Spiromaks can be administered to nursing women only if the expected benefit to the mother outweighs any possible risk to the child.
APPLICATION FOR FUNCTIONS OF THE LIVER
No data on the admission of the drug DuoResp Spiromaks patients with renal insufficiency . Because budesonide and formoterol are derived primarily by the kidneys, with the participation of hepatic metabolism, the patients with severe cirrhosis of the liver can be expected to slow the speed of elimination of the drug
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
No data on the admission of the drug DuoResp Spiromaks patients with hepatic insufficiency . Because budesonide and formoterol are derived primarily by the kidneys, with the participation of hepatic metabolism, the patients with severe cirrhosis of the liver can be expected to slow the speed of elimination of the drug
APPLICATION IN ELDERLY PATIENTS
No need for a special selection of doses for elderly patients .
Before the cessation of treatment is recommended to progressively reduce the dose of the drug. Not recommended rapidly cancel treatment.
DuoResp Spiromaks not used for the initial selection of therapy in the early stages of the treatment of bronchial asthma.
Receiving formoterol may cause lengthening of the interval QT.
Increased frequency receiving bronchodilators as emergency drugs indicates worsening of the underlying disease and serves as a basis for revising tactics treatment of bronchial asthma. Sudden and progressive deterioration of symptom control of asthma or COPD is potentially life-threatening condition and requires immediate medical intervention. In this situation, should consider the possibility of increasing doses of corticosteroids or addition of systemic anti-inflammatory therapy, e.g., a course of oral corticosteroids or antibiotic treatment in case of infection attachment. Patients are advised to always carry emergency medications (beta 2 -adrenomimetiki short-acting).
Should pay attention to the patient's need for regular ingestion DuoResp Spiromaks in accordance with the selected dose even in the absence of symptoms.
Treatment with DuoResp Spiromaks should not be initiated during an exacerbation or significant worsening of asthma.
As with any other inhalation therapy, paradoxical bronchospasm may occur with increased wheezing immediate postdose formulation. In this connection should be discontinued therapy with DuoResp Spiromaks reconsider the tactics of treatment and, if necessary, appoint an alternative therapy.
Systemic effects can occur when taking any inhaled corticosteroids, especially when taking drugs at high doses for an extended period of time. Systemic manifestation is less likely during inhalation therapy than with oral corticosteroids. The possible systemic effects include adrenal suppression, reduction of bone mineral density, cataract and glaucoma.
Based on the limited research data on chronic administration of corticosteroids, it can be assumed that the majority of children and adolescents receiving therapy with inhaled budesonide ultimately achieve normal adult rate of growth. However, the reported low (about 1 cm), short delay in growth mainly during the first year of treatment.
Because of the potentially possible effect of inhaled corticosteroids on bone mineral density should pay particular attention to patients taking high doses of the drug over a prolonged period with the presence of risk factors for osteoporosis. Studies prolonged use of inhaled budesonide in children at an average daily dose of 400 micrograms (metered dose) or adults in a daily dose of 800 micrograms (metered dose) showed no significant effect on bone mineral density. No data on the effect of high doses of the drug DuoResp Spiromaks on bone mineral density.
If there is reason to believe that against the background of previous systemic therapy SCS was disturbed adrenal function, precautions should be taken when transferring patients to treatment with DuoResp Spiromaks.
Advantages budesonide inhalation therapy are generally minimize the necessity of oral steroids however patients discontinuing therapy with oral corticosteroids for a long time can be maintained adrenal insufficiency. Patients who last needed urgently high doses of corticosteroids or to give long-term treatment with inhaled corticosteroids at high doses, may also be in this risk. It is necessary to provide for the appointment of additional corticosteroids during periods of stress or surgery.
It is recommended to instruct the patient about the need to rinse the mouth with water after inhalation to prevent the development of oral mucosal candidiasis.
Care should be taken when treating patients with elongated QT intervalc . Receiving formoterol may cause lengthening of the interval QT c .
Should review the need for, and dose of inhaled corticosteroids in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.
When coadministered beta 2 -adrenomimetikov with drugs that may induce or enhance the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics may increase gipokaliemicheskogo effect of beta 2 -adrenomimetikov.
It is necessary to take special precautions in patients with unstable asthma patients treated with short-acting bronchodilators, for removal during exacerbation episodes of severe asthma, because the risk of hypokalemia increased by hypoxia and in other conditions when the increased probability of developing gipokaliemicheskogo effect. In such cases it is advisable to control the content of potassium in serum.
The treatment should monitor the concentration of blood glucose in patients with diabetes.
Impact on the ability to drive vehicles and manage mechanisms
DuoResp Spiromaks drug has no effect on ability to drive and use machines. May have little influence in the manifestation of side effects. Caution should be exercised when driving and mechanisms due to the possibility of side effects.
Symptoms: an overdose of formoterol - tremor, headache, palpitations. In some cases, it was reported on the development of tachycardia, hyperglycemia, hypokalemia, prolongation of the QT interval c , arrhythmia, nausea and vomiting.
In acute overdose of budesonide, even in large doses, it is not expected clinically significant effects. In chronic taking excessive doses can manifest systemic effects of corticosteroids such as hypercortisolism and adrenal suppression.
Treatment: is supportive and symptomatic therapy. If necessary, the withdrawal of the drug DuoResp Spiromaks due to overdose of formoterol should consider the appointment of the relevant SSC.
Receiving patients with acute bronchial obstruction formoterol in a dose of 90 mg for 3 hours safe.
Receiving ketoconazole at a dose of 200 mg 1 time / day increases the concentration of budesonide in the plasma after oral administration (3 mg single dose) when coadministered, on average, 6 times. When assigning ketoconazole 12 hours after receiving the last budesonide concentration in plasma increased on average 3 times.Information about such interaction with budesonide inhalation when the application is absent, but one should expect a significant increase in the plasma concentration of the drug. Because data for the dose recommendation for the selection are not available, to avoid the above combination of drugs. If possible, the time intervals between administration of ketoconazole and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent inhibitors of CYP3A4, probably also can greatly increase the concentration of budesonide in the plasma.
Blockers? 2 -adrenoceptor capable of reducing the intensity of formoterol action. A combination of formoterol + budesonide should not be administered simultaneously with beta-blockers (including eye drops) unless required cases.
Co-administration of the combination formoterol + budesonide and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), MAO inhibitors, tricyclic antidepressants may prolong 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 beta 2 -adrenomimetikam.
Simultaneous use of MAO inhibitors and drugs with similar properties such as furazolidone and procarbazine, may cause increased blood pressure. There is an increased risk of arrhythmias in patients with general anesthesia halogenated hydrocarbons drugs.
With the simultaneous application of a combination formoterol + budesonide and other beta-adrenergic drugs may increase the side effects of formoterol. As a result of beta 2 -adrenomimetikov possible development of hypokalemia which may be exacerbated by the concomitant treatment of xanthine derivatives, corticosteroids or diuretics. Hypokalemia may enhance susceptibility to the development of arrhythmias in patients receiving cardiac glycosides.
There was no interaction between formoterol and budesonide with other drugs used to treat asthma.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 2 years.
The shelf life of the drug after opening the wrapping foil - 6 months.