2010/06/19

Symbicort turbuhaler

Dosage form, composition and packaging

Powder for inhalation dose in the form of granules from white to almost white, mostly round shape.

1 dose (delivered) - budezonid - 80 micrograms - of formoterol fumarate dihydrate - 4.5 micrograms.

Excipients: lactose monohydrate.

Pharmacological action

Combined medication for the treatment of bronchial asthma. It contains formoterol and budesonide, which have different mechanisms of action and show additive effect in reducing the frequency of exacerbations of asthma. Budesonide - GCS, after inhalation of anti-inflammatory effect on the airways, which lasts several hours and is dose-dependent. Reduces severity of symptoms and frequency of exacerbations of asthma. In the appointment of inhaled budesonide in the form of notes lower incidence of serious side-effects than with systemic SCS. Decreases edema of the mucous membrane of the bronchi, mucus production, education, sputum and airway hyperreactivity. The exact mechanism of anti-inflammatory action of GCS is not known.

Formoterol - a selective ß2-adrenoceptor agonist. Causes relaxation of smooth muscles of the bronchi in patients with reversible respiratory obstruction. Bronchodilator effect is dose-dependent, occurs within 1-3 minutes after inhalation and is kept for at least 12 hours after receiving a single dose. In clinical studies found that the combined use of formoterol and budesonide reduced the severity of symptoms of asthma, improving lung function and reduced the frequency of exacerbations of the disease.

Effects of Symbicort turbuhaler on lung function corresponds to the action monotherapies, the combination of budesonide and formoterol and budesonide than one action. Not mentioned reduction of asthma over time. The drug has a good tolerability.

During the course of turbuhaler Symbicort as maintenance therapy for 12 weeks in children aged 6 to 11 years (two inhalations of 80 / 4,5 mcg / inhalation 2 times / day) improves lung function and was awarded with a good tolerability, according to compared with the corresponding dose of budesonide turbuhaler.

In patients with severe chronic obstructive pulmonary disease (baseline FEV | - 36%) in the intake of Symbicort turbuhaler showed a significant decrease in the frequency of exacerbations of the disease compared with patients receiving therapy just as formoterol or placebo (mean frequency of exacerbations compared with 1.4, 1 8-1,9 in the placebo / formoterol). There was no difference between the reception and Symbicort Formoterol against the values of FEV1.

Farmakokinektika

Absorption

Symbicort turbuhaler bioekvivalenten respective monotherapies (budesonide and formoterol) in respect of their systemic action. Despite this, there was a slight increased suppression of cortisol after administration of Symbicort turbuhaler compared with monotherapies. This difference does not affect the clinical safety of Symbicort turbuhaler. Evidence of pharmacokinetic interaction between budesonide and formoterol are not available. Pharmacokinetic parameters of budesonide and formoterol were comparable after their admission as monotherapies and as part of Symbicort turbuhaler.

When using the combined formulation of budesonide AUC was slightly more is absorbed faster and the magnitude of C max was higher, C max formoterol coincide with those for monotherapies. Nebulised budesonide is rapidly absorbed, reaching C max after 30 min. The average dose of budesonide, got into the lungs after inhalation via turbuhaler is 32-44% of the delivered dose. Systemic bioavailability of approximately 49% of the delivered dose. In children aged 6 to 16 years, the average dose of budesonide that has entered the lungs after inhalation via turbuhaler does not differ from that of adult patients (final concentration of the drug in blood plasma was not determined).

Inhaled formoterol is rapidly absorbed, reaching C max within 10 min after inhalation. Studies have shown that the average dose of formoterol, got into the lungs after inhalation via turbuhaler is 28-49% of the delivered dose. Systemic bioavailability - about 61% of the delivered dose.

Distribution

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

Metabolism

Formoterol is metabolized in the liver by conjugation with the formation of active O-demethylated metabolites, but mostly - inactivated conjugates. Budesonide undergoes intensive biotransformation (90%) in the "first pass" through the liver with the formation of metabolites with low glucocorticoid activity. The metabolism of budesonide is carried out mainly with the participation of the enzyme CYP3A4. Glucocorticoid activity of the major metabolite - 6-ß-gidroksibudesonida and 16-alpha-gidroksiprednizolona - less than 1% of similar activity of budesonide. There is no evidence of interaction of metabolites or substitution reaction between budesonide and formoterol.

Withdrawal

After inhalation of 8-13% of delivered dose of formoterol is excreted unchanged in the urine. Formoterol has a high systemic clearance (approximately 1.4 l / min);

T1 / 2 is an average of 17 hours

Budesonide is excreted in the urine as metabolites or in the form of conjugates, and only in small quantities - unchanged. Budesonide has a high systemic clearance (approximately 1.2 l / min).

Pharmacokinetics in special clinical situations

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 may be elevated in patients with liver zabolevniyami.

Statement
bronchial asthma (not controlled by inhaled GCS and beta2-sympathomimetics as a short-acting therapy on demand, or adequately controlled with inhaled GCS and ß2-adrenoagonists long-acting) - as a maintenance therapy and cupping;
symptomatic therapy in patients with severe chronic obstructive pulmonary disease (FEV <50% of the estimated current level) and repeated exacerbations in history, in the presence of pronounced symptoms, despite treatment with bronchodilators long-lasting.

Dosage regimen

Bronchial asthma

Symbicort turbuhaler not intended for initial treatment of bronchial asthma and lung persistiruyushego intermittent flow. Selection of doses comprising Symbicort turbuhaler, conducted individually, and depending on the severity of the disease. It is necessary to consider not only at the beginning of combination therapy, but after changing the dose. In the event that certain patients require different doses of a combination of active substances than in the drug Symbicort turbuhaler should designate a separate betagadrenomimetiki and / or MCS in separate inhalers. The dose should be reduced to the lowest against which remains the optimal control of symptoms of bronchial asthma. Patients should be under constant medical supervision for the proper selection of a dose Symbicort turbuhaler. When the full control of asthma symptoms on a background of the minimum recommended dose, the next step you can try the appointment of monotherapy with inhaled GCS.

There are two approaches to the appointment of therapy Symbicort turbuhaler.

A. turbuhaler Symbicort as maintenance therapy: a drug prescribed as maintenance therapy in combination with a separate betag-adrenostimulyatorov short action for relief of attacks. The patient must always carry an inhaler with a separate betag-adrenostimulyatorov short action for relief of attacks.

Adults (18 years and older) designate turbuhaler Symbicort 80/4.5 mcg / dose and 160/4.5 mcg / dose for 1-2 inhalations 2 times / day. If necessary, the dose can be increased to 4 inhalations 2 times / day.

Teens (12-17 years) designate turbuhaler Symbicort 80/4.5 mcg / dose and 160/4.5 mcg / dose for 1-2 inhalations 2 times / day.

Children under the age of 6 prescribe Symbicort turbuhaler 80/4.5 mcg / dose for 1-2 inhalations 2 times / day.

After achieving optimal control of asthma symptoms on a background of taking the medication 2 times per day is recommended to titrate the dose to the smallest effective up to receive a once a day, in those cases where the opinion of the doctor patient requires supportive therapy in combination with long-acting bronchodilators.

Increasing the frequency of beta 2-adrenostimulyatorov short-acting is an indicator of the deterioration of overall control of the disease and requires a revision of anti-asthma therapy.

B. Symbicort turbuhaler as maintenance therapy for relief of seizures: the drug can be prescribed as continuous as maintenance therapy, as well as treatment on demand in case of attacks. The patient must always carry turbuhaler Symbicort for relief of attacks.

Turbuhaler Symbicort as maintenance therapy and cupping is particularly indicated for patients with inadequate asthma control and the need to frequently use the drug to treat seizures, and specifying a history of bronchial asthma exacerbations requiring medical intervention.

Need to monitor closely the appearance of dose-dependent side effects in patients using a large number of inhalations for relief of attacks.

Adults (18 years and older) designate Symbicort turbuhaler 80 / 4,5 mcg / dose and 160/4.5 mcg / dose, the recommended dose - 2 inhalations per day: 1 inhalation in the morning and evening, or 2 inhalations 1 time / day only in the morning or evening. If you experience symptoms should be the appointment of 1 additional inhalation. With further increase of symptoms within a few minutes appoint another 1 additional inhalation, but no more than 6 inhalations for relief of an attack. Usually does not require the appointment of more than 8 inhalations per day, but you can increase the number of inhalations to 12 per day for a short time. Patients who use more than 8 inhalations per day is recommended revision of therapy. COPD

Adults prescribed Symbicort turbuhaler 160/4.5 mcg / dose of 2 inhalations 2 times / day. No need for a special selection of the dose for elderly patients.

No data on the use of Symbicort Turbuha ¬ Teller in patients with renal or hepatic insufficiency. As budesonide and formoterol are derived primarily involving liver metabolism, the patients with severe cirrhosis of the liver can be expected to slow the rate of excretion of the drug.

Terms of Use turbuhaler

The mechanism of action turbuhaler is such that when a patient inhales through the mouthpiece, the flow of air carries with it a medicinal substance in the respiratory tract.

Should instruct the patient:
carefully examine the "Instruction on the Application ¬ tion" turbuhaler;
breathe heavily and deeply through the mouthpiece to ensure getting the optimal dose of the drug into the lungs;
never exhale into the mouthpiece;
in order to minimize the possibility of fungal infections of oropharynx, rinse your mouth with water after each inhalation. It is also necessary to rinse your mouth with water after inhalation to edema and symptoms of the case of candidiasis of the oral mucosa and pharynx.

The patient may not taste or feel the product after use turbuhaler, due to a small amount of delivered material.

Instructions for use turbuhaler

Turbuhaler - multidose inhaler, which allows dose and inhale the drug in very tiny doses. If you inhale the powder from turbuhaler delivered to the lungs, so it is important that the patient is strong and deep breaths through the mouthpiece.

Before first use turbuhaler need to prepare for work:
Unscrew and remove the cap.
Hold the inhaler upright red feeder bottom. Do not keep the inhaler in the mouthpiece during the rotation dosing. Turn the dispenser until it stops in one direction, and then also the way - in the opposite direction.

Perform this procedure twice. Now the inhaler ready for use, repeat this. procedure for the preparation turbuhaler to work before each use is not required.

To receive a single dose of the patient must perform the following procedures:
Unscrew and remove the cap.
Hold the inhaler upright red feeder bottom. Do not keep the inhaler in the mouthpiece during the rotation dosing. In order to measure out the dose, dosing turn to lock in one direction, and then also the way - in the opposite direction.
Exhale. Do not exhale through the mouthpiece.
Carefully place the mouthpiece between your teeth, your lips and inhale strongly and deeply through your mouth. The mouthpiece does not chew and do not compress your teeth.
Before you exhale, pull out the inhaler from the mouth.
If you want to inhalation of more than one dose, repeat paragraphs. 2-5.
Close inhaler cap, check that the inhaler cap was thoroughly screwed.
Rinse mouth with water without swallowing.

It is impossible to remove the mouthpiece, because He is enshrined in the inhaler and not withdrawn. Mouthpiece turbuhaler rotates, but do not turn it unnecessarily. As the number of inhaled powder is very small, you can not taste the powder after inhalation. It is absolutely accurate compliance manual provides inhalation (ingalirovanie) required dose. If before taking the drug by mistake was repeated the procedure for loading the inhaler more than once, the inhalation of patients will still receive one dose of the drug. This indicator shows the total number of doses calibrated doses. The sound which is heard when shaking the inhaler, is made desiccating agent, and not drugs.

The need to replace the inhaler

The indicator shows the approximate number of doses of doses remaining in the inhaler, calculated doses to fill turbuhaler begins with the 60 th or 120 th dose (depending on the total number of doses purchased turbuhaler). The indicator shows the interval in 10 doses, so it does not show every metered (loaded) dose. Turbuhaler deliver the required dose of the drug, even if no noticeable change in the window display of doses.

The appearance of a red background in the window display of doses means that turbuhaler still have 10 doses of the drug. When the number 0 on a red background in the middle of the window dose inhaler should be discarded. It should be noted that even when the window indicator shows the number 0, dispenser continues to turn. However, the dose indicator stops to record the number of doses (ceases to move) and in the window dose inhaler remains the number 0.

Cleaning

Regularly (1 time per week) should be cleaned outside of the mouthpiece with a dry cloth. Do not use water or other liquid to clean the mouthpiece.

Utilization

Caution must be exercised when handling used inhaler and remember that within the inhaler may be a certain amount of the drug.

Side effect

Against the backdrop of a joint appointment of two drugs, there has been increasing the frequency of adverse reactions. The most common adverse reactions associated with drug intake, are such pharmacologically expected to betagadrenomimetikov unwanted side effects, like tremors and tachycardia, which usually have a moderate degree of severity and pass a few days after starting treatment.

In the application of budesonide in patients with COPD bruises and pneumonia occurred at a frequency of 10% and 6% respectively, compared to 4% and 3% in the group with placebo.

Quired for central nervous system: often - head ¬ Nye pain, less often - psychomotor agitation, anxiety, nausea, dizziness, sleep disorders are very rare - depression, behavioral disturbances (mainly in children), breach of taste.

Since the cardiovascular system: often - heartbeat; less frequently - tachycardia rarely - atrial fibrillation, supraventricular tachycardia, extrasystoles, very rarely - angina, blood pressure fluctuations.

From the kostnomyshechnoy system: often - tremor, less often - muscle cramps.

In the respiratory sistemy.chasto (> 1 / 100, but - candidiasis of the oral mucosa and pharynx, lung irritation in the throat, cough, hoarseness; rarely - bronchospasm.

Dermatological reactions: less often - bruises; rare - exanthema, rash, itching, dermatitis, angioedema.

Metabolic Disorders: rare - hypokalemia, very rarely - hyperglycemia, symptoms of systemic effects of GCS (including hypoadrenalism). Systemic effects of inhaled GCS may occur while taking the drug in high doses for long periods. The use of beta 2-sympathomimetics may result in an increase in blood insulin, free fatty acids, glycerol, ketone derivatives.

Contraindications
Children under 6 years
Hypersensitivity to budesonide, formoterol or inhaled lactose.

Precautions should be applied turbuhaler Symbicort in patients with pulmonary tuberculosis (active or inactive form), fungal, viral or bacterial infections of the respiratory system in patients with thyrotoxicosis, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortalnym stenosis, severe hypertension, aneurysm of any location or other serious cardiovascular diseases (coronary heart disease, tachy-arrhythmia or heart failure, severe), with lengthening of the interval QT (formoterol may cause lengthening of the interval QTC).

Pregnancy and lactation

No clinical data on the use of Symbicort turbuhaler or combined use of formoterol and budesonide in pregnancy. If pregnancy should be prescribed Symbicort turbuhaler only when the expected benefit of therapy to the mother outweighs the potential risk to the fetus. Should be applied budesonide in the lowest effective dose needed to maintain adequate control of symptoms of asthma.

It is not known whether formoterol allocated and budesonide through breast milk in humans. Symbicort turbuhaler can be assigned to nursing mothers unless the expected benefit of therapy to the mother outweighs the potential risk to the child.

Cautions

We recommend gradually reducing the dose before discontinuation of treatment and is not recommended to abruptly stop therapy.

Turbuhaler Symbicort (80/4.5 mg / dose) was not intended to treat patients with severe bronchial asthma.

Symbicort turbuhaler not intended for the initial selection of therapy in the early stages of treatment of bronchial asthma.

For lack of effectiveness of therapy or exceeding the maximum recommended doses of Symbicort turbuhaler need to review the tactics of treatment. Sudden and progressive deterioration in control of symptoms of asthma or COPD is potentially life-threatening condition and requires urgent medical intervention. In this situation, should consider the possibility of increasing the dose of GCS, ie, the appointment of the course of oral antibiotic treatment GCS, or in case of infection.

Patients should always carry emergency medications, or Symbicort turbuhaler (for patients with asthma using turbuhaler Symbicort maintenance therapy and cupping), betagadrenomimetikm short-acting (for all patients using Symbicort turbuhaler only for maintenance therapy).

Attention is drawn to a patient's need for regular maintenance dose of Symbicort reception turbuhaler in accordance with the chosen therapy, even in the absence of symptoms. Inhalation Symbicort turbuhaler for cupping should be conducted only when there symptoms, but the use of the drug is not indicated for routine prophylactic use, ie before exercise. In these cases demonstrates the use of a separate short-acting bronchodilator.

Treatment Symbicort turbuhaler should not begin during the exacerbation of bronchial asthma. As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate intensification of wheezing after taking the dose. In this connection, it should discontinue therapy Symbicort turbuhaler to reconsider the tactics of treatment and, if necessary, appoint an alternative therapy

Systemic effects may occur when taking any inhaled GCS, especially when taking high doses of drugs over a long period of time. The manifestation of systemic effects are less likely during inhalation therapy than with oral GCS. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.

It is recommended to regularly monitor the growth of children receiving long-term inhaled GCS. In case of growth retardation should reconsider therapy to reduce the dose of inhaled GCS. Should be carefully weighed against the benefits of SCS therapy for a possible risk of growth retardation. When selecting therapy is recommended consultation pediatric pulmonology.

Based on the limited research data on the chronic administration of GCS, we can assume that most children and adolescents receiving treatment by inhaled budesonide ultimately achieve normal adult rate of growth. However, the reported low (about 1 cm), short-term growth retardation, mainly in the first year of treatment. Because of potential actions of inhaled GCS on bone mineral density should pay particular attention to patients taking the drug in high doses for long periods with the presence of risk factors for osteoporosis. Studies of prolonged use of nebulised budesonide in children of average daily dose of 400 micrograms or adults in an average daily dose of 800 mg showed no significant effect on bone mineral density. No data on the action of high doses of the drug on bone mineral density.

If estosnovaniya believe that against the background of previous systemic therapy SCS was disturbed adrenal function, should take precautions when transferring patients to treatment Symbicort turbuhaler.

The advantages of budesonide inhalation therapy, usually minimizes the need for receiving oral GCS, but the patients discontinuing therapy with oral GCS, for a long time may continue adrenal insufficiency. Patients who in the past were in need of urgent admission of high doses of GCS may also be in this risk group. In extreme cases, and any situations that may cause stress, you should always keep in mind the possibility of residual dysfunction of the adrenal glands in these patients. In such situations need to provide adequate treatment of the SCS. Depending on the degree of dysfunction of the adrenal glands may need to consult a specialist prior to the recommended procedures.

It should reconsider the need for and dose inhaled GCS in patients with active or inactive forms of pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.

Should observe special precautionary measures in patients with unstable asthma, short-acting bronchodilators applying for withdrawal seizures in patients with acute severe asthma, because the risk of hypokalemia increases against the background of hypoxia and other conditions where increased likelihood of developing symptoms gipokaliemicheskogo action. In such cases, it is recommended to control the content of potassium in serum.

Admission of patients with acute bronchial obstruction formoterol in a dose of 90 mcg for 3 hours is safe. During the period of treatment should control the concentration of glucose in the blood of patients with diabetes.

Symbicort turbuhaler contains lactose (less than 1 mg / dose). Typically, this amount does not cause problems in patients with lactose intolerance.

Use in Pediatrics

Symbicort turbuhaler not recommended for use in COPD in children younger than 6 years. Turbuhaler Symbicort is not recommended as maintenance therapy and cupping for children and adolescents under the age of 18 years.

Effects on ability to drive vehicles and management mechanisms

Symbicort turbuhaler not affect the ability to drive motor vehicles and management mechanisms. May influence the ability to drive motor vehicles and management mechanisms in the development of side effects.

Overdose

Symptoms: an overdose of formoterol - tremor, headache, tachycardia, in some cases - hyperglycemia, hypokalemia, prolongation of the interval QTC, arrhythmias, nausea, vomiting. In acute overdose of budesonide, even in large doses, is not expected clinically significant symptoms. In chronic receive budesonide in excessive doses can manifest systemic effects SCS, such as hypercorticoidism and adrenal suppression.

In acute bronchial obstruction receiving formoterol in a dose of 90 mcg for 3 h was safe.

Treatment: supportive and shown symptomatic treatment. In case of need to cancel due to an overdose turbuhaler Symbicort Formoterol, incoming and composition of the combined drug, should consider the appointment of the SCS.

Drug Interactions

In simultaneous ingestion of ketoconazole in a dose of 200 mg 1 time / effect of budesonide in a dose of 3 mg budesonide concentration in plasma increased by an average of 6 times. When receiving ketoconazole at 12 h after administration of budesonide in plasma concentration of the latter increased on average 3 times. The information about such interactions with budesonide inhalation administration is absent, but should expect a noticeable increase in concentration of the drug in blood plasma. Since there is currently no information for recommendations on the selection of doses should be avoided given combination of drugs. If not, then the intervals between doses of ketoconazole and budesonide should be maximized. You should also consider reducing the dose of budesonide. Other potent inhibitors of CYP3A4, may also be significantly increased the content of budesonide in plasma. We do not recommend the appointment of turbuhaler Symbicort as maintenance therapy and cupping the patients receiving potent inhibitors of CYP3A4. 3-adrenoceptor blockers can weaken or inhibit the action of formoterol. Symbicort turbuhaler should not be given simultaneously with beta-blockers (including eye drops), except in cases of extreme necessity. With simultaneous use of Symbicort turbuhaler and quinidine, dizopiramid, procainamide, phenothiazines, antihistamines (terfenadina), MAO inhibitors and tri-cyclic antidepressants may be lengthening the QT interval and increase the risk of ventricular arrhythmias. In addition, levodopa, levothyroxine, oxytocin, and ethanol can reduce the tolerance of the heart muscle to betagadrenomimetikam. In case of simultaneous appointment of MAO inhibitors and drugs with similar characteristics (furazolidone, procarbazine), may increase blood pressure. In the conduct of anesthesia drugs halides ized hydrocarbons during treatment Symbicort turbuhaler there is an increased risk of arrhythmias in patients. At the same time taking Symbicort turbuhaler and other agonists (5-adrenergic receptors may be increased side effects of formoterol. Gipokaliemicheskoe action betag-sympathomimetics may be increased, while the appointment of xanthine derivatives, minerals, derivatives of the SCS and diuretics. Hypokalemia increases the susceptibility to the development of arrhythmias in patients receiving cardiac glycosides . There was no interaction of budesonide with other drugs used to treat asthma.

Terms and Conditions of storage

The drug should be stored at temperatures not above 30 ° C in the reach of children. Shelf life - 2 years.