DuoResp Spiromax - instructions for use, dose, side effects, contraindications

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Dosage form: & nbsppowder for inhalation dosed

Composition:

The 1 delivered dose contains: active substances budesonide (micronized) 160 μg / 320 μg, formoterol fumarate dihydrate (micronized) 4.5 μg / 9 μg; adjuvant: lactose monohydrate 5 mg / 10 mg.

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

Description:

A white or almost white powder with no visible lumps or inclusions placed in a multi-dose powder inhaler with a translucent lid for a red mouthpiece. The inhaler should be without visible damage. The dosing display window should show No. 120 for a dosage of 160 / 4.5 μg / dose and No. 60 for a dosage of 320/9 μg / dose.

Pharmacotherapeutic group:Bronchodilator combined (beta2-adrenomimetic selective + glucocorticosteroid local)

ATX: & nbsp

Formoterol and budesonide

Pharmacodynamics:

The drug DuoResp Spiromax contains formoterol and budesonide, which have different mechanisms of action and have an additive effect on 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 at the same time as maintenance therapy and for relief of seizures, or as a supporting therapy for bronchial asthma.

Budesonide

Budesonide is a glucocorticosteroid that, after inhalation, has a rapid (within a few 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 glucocorticosteroids. Reduces the severity of the bronchial mucosa edema, mucus production, sputum formation and airway hyperreactivity. The exact mechanism of the anti-inflammatory effect of glucocorticosteroids is unknown.

Formaterol

Formoterol is a selective β2-adrenergic receptor agonist, which, after inhalation, causes rapid and prolonged relaxation of bronchial smooth muscles in patients with reversible airway obstruction.Broncholytic dose-dependent action occurs rapidly, within 1-3 minutes after inhalation and remains for at least 12 hours after taking a single dose.

Budesonide + Formoterol

Bronchial asthma

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, β2A short-acting adrenostimulator. Hc there was a decrease in progiva-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 treated with budesonide / formoterol as maintenance therapy and to relieve 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 budesonide as maintenance therapy and β2-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 the appointment of salbutamol and formoterol.

Chronic obstructive pulmonary disease

In patients with severe COPD, with the use of DuoResp Spiromax, there was a significant reduction in the frequency of exacerbations of the disease compared with patients receiving only formoterol or placebo (mean frequency of exacerbations 1.4 compared with 1.8-1.9 in the placebo / formoterol group). There was no difference between taking DuoResp Spiromax and formoterol with a forced expiratory volume index for the first second (FEV₁).

Pharmacokinetics:

Suction. 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, when administered as a combination preparation, the area under the concentration-time curve (AUC) slightly more, the absorption of the drug is faster and the maximum concentration in the blood plasma is higher.

For formoterol, when administered in a combination preparation, the maximum concentration in the blood plasma coincides with that for a mono drug.

Inhalable budesonide quickly absorbed and reaches the maximum concentration in the plasma 30 minutes after the inhalation. The average dose of budesonide.got into the lungs after the 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, which got into 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).

Inhalable formoterol quickly absorbed and reaches the maximum concentration in the blood plasma 10 minutes after the inhalation. The average dose of formoterol, which fell into the lungs after inhalation, is 28-49% of the delivered dose. Systemic bioavailability is about 61% of the delivered dose.

Distribution. About 50% of formoterol and 90% of budesonide bind 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 is subjected to intensive biotransformation (about 90%) during the first passage through the liver with the formation of metabolites with low glucocorticosteroid activity.Glucocorticosteroid activity of the main metabolites of 6-β-hydroxybuddesonide and 16-α-hydroxy-prednisolone 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.

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 system clearance (approximately 1.4 l / min); the half-life of the drug is an average of 17 hours. Budesonide metabolized predominantly with the participation of an enzyme CYP3A4. Metabolites of budesonide are excreted in the urine in unmodified form or in the form of conjugates. In urine, only a small amount of unmodified budesonide is found. Budesonide has a high system clearance (approximately 1.2 l / min). 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.

Indications:

- Bronchial asthma (insufficiently controlled by the intake of inhaled glucocorticosteroids and beta β2-adrenostimulators of short-acting or adequately controlled by inhaled GCS and long-acting β2-adrenostimulants).

- COPD (symptomatic therapy in patients with severe chronic obstructive pulmonary disease (FEV)₁ <50% of the estimated calculated level) and with repeated exacerbations in the anamnesis, which have severe symptoms of the disease, despite long-acting bronchodilator therapy).

Contraindications:

- Hypersensitivity to budesonide, formoterol or inhaled lactose.

- Children under 18 years old.

Carefully:

Tuberculosis of the lungs (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 (coronary heart disease, tachyarrhythmia or severe heart failure) , lengthening the interval QT (taking formoterol may cause lengthening QTc-interval), lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Pregnancy and lactation:

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

During pregnancy, DuoResp Spiromax should be used only when the benefits of using the drug exceed the potential risk to the fetus. The lowest effective dose of budesonide needed to maintain adequate control of asthma symptoms should be used. Inhalable budesonide excreted in breast milk, however, when applied in therapeutic doses, no effect on the child was noted. It is not known whether formoterol in the breast milk of women. The drug DuoResp Spiromax can be prescribed to nursing women only if the expected benefit for the mother is greater than any possible risk to the child.

Dosing and Administration:

Bronchial asthma

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. It's necessary to take into account not only at the beginning of treatment with combined preparations, but also with the change in the maintenance dose of the drug.

In the event that individual patients require different doses of a combination of active components than in Preparation DuoResp Spiromaks should assign β2-adrenoceptor agonists and / or corticosteroids 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 asthma while taking the drug twice a day is recommended to titrate the dose to the minimum effective until the drug once a day, in cases where, in the judgment of the physician, the patient requires supportive therapy in combination with a bronchodilator long-acting .

Adults (18 years and over):

The drug DuoResp Spiromax 160 / 4.5 mcg / dose as maintenance therapy 1-2 inhalations twice a day. If necessary, it is possible to increase the dose to 4 inhalations twice a day.The patient should always have a separate inhaler with β2-adrenostimulyagorom short action for relief of attacks. Increased frequency of use of β2-adrenostimulants short-acting is an indicator of the deterioration of general control over the disease and requires revision of anti-asthma therapy.

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

The drug DuoResp Spiromax can be prescribed as a permanent maintenance therapy, hack and as a therapy on demand in the event of seizures. As maintenance therapy and for relief of seizures, it is especially indicated for patients with:

- insufficient 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 per day, 1 inhalation is taken in the morning and in the evening, or 2 inhalations once in the morning or only in the evening.For some patients, a maintenance dose may be prescribed drug DuoResp Spiromax 160 / 4.5 mcg / dose 2 inhalations twice a day. 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

1 inhalation twice a day. If necessary, it is possible to increase the dose to 2 inhalations twice a day.

After achieving the optimal control of the symptoms of bronchial asthma on the background of taking the drug twice a day, it is possible to reduce the dose to the lowest effective, up to a dose once a day.

COPD

Adults (18 years and over):

DuoResp Spiromax 160 / 4.5 mcg / dose 2 inhalations of the drug twice daily.

DuoResp Spiromax 320/9 mcg / dose 1 inhalation of the drug twice daily.

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. How budesonide and formoterol are excreted mainly by the kidneys, with the participation of hepatic metabolism, then in patients with severe cirrhosis of the liver, a slowing down of the drug release rate can be expected.

Mode of application

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 is heard click and it will 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.

Side effects:

Against the background of the joint appointment of two drugs, there was no increase in the incidence of adverse reactions. The most common adverse reactions associated with taking the drug are those pharmacologically expected for β2-adrenergic agents, undesirable 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).

The frequency is defined as follows: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1 / 1000), very rarely (<1/10000) and is unknown (can not be estimated from the available information).

Class of organ systems	Frequency	Side effect
Immune system disorders	Rarely	Hypersensitivity reactions of immediate and delayed type (exanthema, urticaria, pruritus, dermatitis of angioedema and anaphylactic reaction)
Disorders from the endocrine system	Rarely	Cushing's syndrome, adrenal suppression, slowing of growth, lowering of bone mineral density
Disorders from the metabolism and nutrition	Rarely	Hypokalemia
Disorders from the metabolism and nutrition	Rarely	Hyperglycemia, signs or symptoms of systemic glucocorticosteroid effects (including adrenal hypofunction)
Disorders from the psyche	Infrequently	Excitation, psychomotor agitation, anxiety, sleep disturbances
Disorders from the psyche	Rarely	Depression, behavioral disorders
Disturbances from the nervous system	Often	Headache, tremor
	Infrequently	Dizziness
	Rarely	Disturbances of taste
Disturbances on the part of the organ of sight	Rarely	Cataract and glaucoma
Heart Disease	Often	Palpitation
	Infrequently	Tachycardia
	Rarely	Arrhythmia (eg, atrial fibrillation, supraventricular tachycardia, extrasystole)
	Rarely	Angina pectoris, lengthening interval QT
Vascular disorders	Rarely	Blood Pressure Fluctuations
Disturbances from the respiratory system, chest and mediastinal organs	Often	Candidiasis of the mucous membrane of the mouth and throat, irritation of the pharynx, cough, hoarseness
	Rarely	Bronchospasm
	Rarely	Paradoxical bronchospasm
Disorders from the gastrointestinal tract	Infrequently	Nausea
Disturbances from the skin and subcutaneous tissues	Infrequently	Bleeding
Disturbance of musculoskeletal and connective tissue	Infrequently	Muscle cramps

The systemic effect of inhaled glucocorticosteroids can occur when taking high doses for a long time. The use of β2-adrenomimetics can lead to an increase in the blood levels of insulin, free fatty acids, glycerol and ketone derivatives.

Overdose:

Symptoms overdose of formoterol: tremor, headache, heart palpitations. In some cases, reported the development of tachycardia, hyperglycemia, hypokalemia, lengthening QTc-Interval. arrhythmias, nausea and vomiting.

If you need to cancel the drug DuoResp Spiromax due to an overdose of formoterol, which is part of the combination drug, you should consider the appointment of an appropriate glucocorticosteroid.

Treatment: supportive and symptomatic. Receiving patients with acute bronchial obstruction formoterol at a dose of 90 mcg for 3 hours is safe.

In acute overdose of budesonide. even in significant doses, no clinically significant effects are expected. When chronic intake of excessive doses, the systemic action of glucocorticosteroids, such as hypercorticism and suppression of adrenal function, may manifest itself.

Interaction:

The administration of 200 mg of ketoconazole once a day raises the concentration in the plasma of oral budesonide (a single dose of 3 mg) when administered jointly, on average, 6-fold. With the appointment of ketoconazole 12 hours after the administration of budesonide, the concentration in the plasma of the latter increased, on average, 3-fold.Information on this interaction with inhaled budesonide is absent, but a noticeable increase in the concentration of the drug in the blood plasma should be expected. Since data for recommendations for dose selection are not available, the above combination of drugs should be avoided. If possible, the time intervals between administration of ketoconazole and budesonide should be maximized. You should also consider the possibility of reducing the dose of budesonide. Other powerful inhibitors CYP3A4, probably, can also significantly increase the concentration of budesonide in plasma.

Blockers of β2-adrenergic receptors can weaken the action of formoterol. The combination formoterol + budesonide should not be prescribed simultaneously with β-blockers (including eye drops), except for forced cases. Combination Combination formoterol + budesonide and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase (MAO) inhibitors and tricyclic antidepressants may prolong the interval QT and increase the risk of ventricular arrhythmias.

Besides, levodopa, levothyroxine. oxytocin and alcohol can reduce the tolerance of the heart muscle to β2-adrenomimetics.

Simultaneous use of MAO inhibitors, as well as drugs with similar properties, such as furazolidone and procarbazine. can cause an increase in blood pressure. There is an increased risk of arrhythmia in patients with general anesthesia with preparations of halogenated hydrocarbons.

If the combination is applied simultaneously formoterol + budesonide and other β-adrenergic drugs may increase the side effects of formoterol. As a result of the application of β2-adrenomimetics hypokalemia may occur, which can be intensified by concomitant treatment with xanthine derivatives, glucocorticosteroids or diuretics. Hypokalemia may increase predisposition to the development of arrhythmias in patients taking cardiac glycosides.

No interaction of budesonide and formoterol with other medications used to treat bronchial asthma was noted.

Special instructions:

It is recommended to gradually reduce the dose of the drug before discontinuing treatment and it is not recommended to abruptly cancel treatment.

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

Reception of formoterol may cause lengthening of the interval QT.

An increase in the frequency of bronchodilators as an emergency medicine, indicates a worsening of the course of the underlying disease and serves as a basis for reviewing the tactics of treating bronchial asthma. An unexpected and progressive deterioration in the management of symptoms of bronchial asthma or COPD is potentially life threatening and requires urgent medical intervention. In this situation, one should consider the possibility of increasing the dose of glucocorticosteroids or the addition of systemic anti-inflammatory therapy, for example, the course of oral glucocorticosteroids or the treatment with antibiotics in case of infection. Patients are advised to constantly have emergency medication (short-acting β2-adrenomimetics).

It is necessary to draw the patient's attention to the need for a regular intake of DuoResp Spiromax in accordance with the selected dose, even in the absence of symptoms of the disease.

Treatment with DuoResp Spiromax 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 taking a dose of the drug. In this connection it is necessary to stop therapy with DuoResp Spiromax, to reconsider treatment tactics and, if necessary, to prescribe alternative therapy. Systemic action may occur when taking any inhaled glucocorticosteroids, especially when taking high doses of drugs for a long period of time. The manifestation of systemic action is less likely when performing inhalation therapy. than when using oral glucocorticosteroids. Possible systemic effects include suppression of adrenal function, reduction of bone mineral density, cataract and glaucoma.

Based on limited data on long-term glucocorticosteroid intake, it can be assumed that most children and adolescents receiving inhaled budesonide therapy.in the end, normal adult growth rates were achieved. At the same time, a slight (about 1 cm) short-term growth retardation was reported, mainly in the first year of treatment.

Because of the potential effect of inhaled glucocorticosteroids on bone mineral density, particular 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 prolonged use of inhaled budesonide in children at an average daily dose of 400 μg (metered dose) or adults at a daily dose of 800 μg (metered dose) did not show a significant effect on bone mineral density. There is no data on the effect of high doses of DuoResp Spiromax on bone mineral density.

If there is reason to believe that against the background of previous systemic therapy of glucocorticosteroids, adrenal function has been disrupted, precautions should be taken when transferring patients to DuoResp Spiromax treatment. The advantages of inhaled budesonide therapy, as a rule,minimize the need for oral steroids, however, in patients who stop oral glucocorticosteroid therapy, adrenal insufficiency may persist for a long time. Patients who in the past needed an urgent intake of high doses of glucocorticosteroids or received long-term treatment with high-dose inhaled glucocorticosteroids may also be at this risk group. It is necessary to provide additional appointment of glucocorticosteroids during the period of stress or surgical intervention. It is recommended to instruct the patient about the need 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 an elongated QTc- interval. Reception of formoterol may cause lengthening QTc- interval.

The need and dose of an inhaled glucocorticosteroid in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system should be reviewed.

With the joint appointment of β2-adrenomimetics with drugs that can cause or exacerbate the hypokalemic effect, for example, xanthine derivatives, steroids or diuretics, possibly increasing the hypokalemic effect of β2-adrenomimetics. Special precautions should be taken in patients with unstable bronchial asthma who use short-acting bronchodilators to relieve attacks with exacerbation of severe bronchial asthma, as the risk of hypokalemia increases with hypoxia and other conditions, when the likelihood of developing a hypokalemic effect increases. In such cases it is recommended to monitor the potassium content in the serum.

During the treatment period it is necessary to control the concentration of glucose in the blood in patients with diabetes mellitus.

Effect on the ability to drive transp. cf. and fur:

The drug DuoResp Spiromax does not affect the ability to drive vehicles and mechanisms. May have little effect with side effects. Care must be taken when driving vehicles and mechanisms in connection with the possibility of developing side effects.

Form release / dosage:

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

Packaging:

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 lid of red color. The label is attached to the inhaler. The inhaler is placed in foil. 1 or 3 inhalers together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Shelf life of the drug after the opening of the foil wrapper - 6 months.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003678

Date of registration:14.06.2016

Expiration Date:14.06.2021

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

Norton Waterford Trading as IVAX Pharmaceuticals Ireland Ireland

Representation: & nbspTeva Teva Israel

Information update date: & nbsp03.04.2017

Illustrated instructions

Instructions

DuoResp Spiromax (DuoResp Spiromax)