Pharmacological action Symbicort Inhaler
Combination drug for the treatment of bronchial asthma. 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 has anti-inflammatory effects on the airways, which lasted several hours and is dose-dependent. Reduces the severity of symptoms and exacerbations of asthma. In the appointment of budesonide in the form of inhalations indicated a lower incidence of serious adverse effects than with systemic corticosteroids. Reduces the severity of edema of bronchial mucosa, mucus production, education, sputum and airway hyperresponsiveness. The exact mechanism of anti-inflammatory action of GCS is not known.
Formoterol – a selective agonist of β2-adrenergic receptors. Causes relaxation of smooth muscles of the bronchi in patients with reversible airway obstruction. Bronchodilator effect is dose dependent, occurs within 1-3 minutes after inhalation and lasts 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 asthma symptoms, improve lung function and reduced the frequency of exacerbations of the disease.
Symbicort Turbuhaler effect on lung function corresponds to the effect of the combination of budesonide and formoterol monotherapies, and more than one effect of budesonide. There was no reduction of asthma over time. The drug is well tolerated. The drug is well tolerated.
In patients receiving Symbicort Turbuhaler as maintenance therapy for 12 weeks in children aged 6 to 11 years (two inhalations of 80/4.5 mcg / inhalation 2 times / day) improved lung function and was marked by a good tolerability, compared with corresponding dose of budesonide Turbuhaler.
In patients with severe chronic obstructive pulmonary disease (baseline FEV1 – 36%) in patients receiving Symbicort Turbuhaler experienced a significant reduction in the frequency of exacerbations of the disease compared to patients receiving therapy just as formoterol or placebo (mean frequency of exacerbations compared with 1.4 1.8-1.9 placebo / formoterol).
There was no difference between taking Symbicort and formoterol on the values of FEV1.
Pharmacokinetics Symbicort Inhaler
Suction
Symbicort Turbuhaler bioequivalent to the corresponding monotherapies (budesonide and formoterol) in respect of their systemic action. Despite this, noted a slight increase suppression of cortisol after administration of Symbicort Turbuhaler compared with monotherapy. This difference does not affect the clinical safety of Symbicort Turbuhaler. Proof of pharmacokinetic interaction of 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.
In applying the combined formulation of budesonide AUC was slightly greater drug absorption is rapid and the value of Cmax was higher; Cmax formoterol coincide with those of monotherapy. Inhaled budesonide is rapidly absorbed and reaches a Cmax within 30 min. The average dose of budesonide, which fell into the lungs after inhalation via Turbuhaler is 32-44% of the delivered dose. Systemic bioavailability is about 49% of the delivered dose. In children aged 6 to 16 years, the average dose of budesonide, which fell into the lungs after inhalation via Turbuhaler, does not differ from that of adult patients (final drug concentration in plasma was not determined).
Inhaled formoterol is rapidly absorbed and reaches a Cmax within 10 min after inhalation. Studies have shown that the average dose of formoterol, which fell 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% of 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 intense biotransformation (90%) for “first pass” through the liver to form metabolites with low glucocorticoid activity. The metabolism of budesonide is predominantly involving the enzyme CYP3A4. Glucocorticoid activity of the major metabolite – 6-β-gidroksibudesonida and 16-α-gidroksiprednizolona – less than 1% of a similar activity of budesonide. There is no evidence of interaction of metabolites or the substitution reaction between the budesonide and formoterol.
Breeding
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 increased in patients with liver disease.
Statement
- Bronchial asthma (not controlled by inhaled corticosteroids and beta2-agonists as a short-acting therapy on demand, or adequately controlled with inhaled corticosteroids and β2-adrenomimetikami long-acting) – as a maintenance therapy and cupping;
- Symptomatic therapy in patients with severe chronic obstructive pulmonary disease (FEV
Dosing regimen Symbicort Inhaler
Bronchial asthma
Symbicort Turbuhaler is not intended for initial treatment of intermittent asthma and mild persistent currents.
Selection of doses that are part of Symbicort Turbuhaler is carried out individually and depending on the severity of the disease. This should be considered not only at the beginning of the treatment of combination therapy, but also a change in dose.
In the event that certain patients require different doses of a combination of active ingredients than in the drug Symbicort Turbuhaler should designate a separate beta2-adrenoceptor agonists and / or corticosteroids in separate inhalers.
The dose should be reduced to the lowest against which to maintain the optimum control of asthma symptoms. Patients should be under constant medical supervision for adequate selection of the dose Symbicort Turbuhaler. In achieving full control of asthma symptoms on the background of the minimum recommended dose, the next step you can try the appointment of monotherapy with inhaled corticosteroids.
There are two approaches to the appointment of therapy SimbikortomTurbuhalerom.
A. Symbicort Turbuhaler as a maintenance therapy: the drug is prescribed as maintenance therapy in combination with a separate beta2-agonist short action for cupping.
The patient must always carry a separate inhaler with beta2-agonist short action for cupping.
Adults (18 years) prescribed Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose, 1-2 inhalations 2 times a day. If necessary, dosage may be increased to 4 inhalations 2 times a day.
Adolescents (12-17 years) prescribed Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose, 1-2 inhalations 2 times a day.
Children under the age of 6 years prescribe Symbicort Turbuhaler 80/4.5 mcg / dose, 1-2 inhalations 2 times a day.
After achieving optimal control of asthma symptoms in patients receiving the drug 2 times a day is recommended to titrate the dose to the smallest effective up to receive a once daily, in cases where the opinion of the doctor patient requires supportive therapy in combination with long-acting bronchodilators.
Increased frequency of beta2-agonist short action is an indication of deterioration of general control of the disease and requires a revision of anti-asthma therapy.
B. Typbyxalep Symbicort as maintenance therapy and cupping: the drug can be given either as continuous maintenance therapy, as well as treatment on demand in case of attack.
The patient must always carry the Symbicort Turbuhaler for cupping.
Symbicort Turbuhaler as maintenance therapy and cupping is particularly indicated for patients with inadequate asthma control and the need for frequent use of drugs for cupping, and specifying a history of asthma exacerbations requiring medical intervention.
Required to closely monitor the emergence of dose-related side effects in patients using a large number of inhalations for cupping.
Adults (18 years) prescribed Symbicort Turbuhaler 80/4.5 mcg / dose and 160/4.5 mcg / dose, the recommended dose – 2 inhalation in the day: 1 inhalation in the morning and evening, or 2 inhalations 1 time per day in the morning or just evening. If you have any symptoms to the appointment of an additional inhalation. With further increase in symptoms for several minutes even appoint 1 additional inhalation, but no more than 6 inhalations for relief of an attack.
Usually not required destination for more than 8 inhalations per day, but you can increase the number of inhalations to 12 a day for a short time. Patients who use more than 8 inhalations per day is recommended revision of the therapy.
COPD
Adults appoint Symbicort Turbuhaler 160/4.5 mcg / dose of 2 inhalations 2 times a day.
No need for a special selection of doses for elderly patients.
No data on the use of Symbicort Turbuhaler in patients with renal or hepatic insufficiency. Since budesonide and formoterol are derived mainly with the participation of hepatic metabolism, the patients with severe cirrhosis of the liver can be expected to slow clearance rate of the drug.
Terms of use Turbuhaler
The mechanism of action Turbuhaler is such that when a patient inhales through the mouthpiece, the air flow carries with it a medicinal substance into the airways.
Must instruct the patient:
- Carefully study the “Instructions for use” Turbuhaler;
- Breathing heavily and deeply through the mouthpiece to ensure getting the optimal dose of the drug into the lungs;
- Never to exhale through the mouthpiece;
- In order to minimize the possibility of fungus oropharynx, rinse your mouth with water after each inhalation. Also need to rinse your mouth with water after inhalation to relieve symptoms, and the case of candidiasis of the mucous membranes of the mouth and pharynx.
The patient may not taste or feel the product after use Turbuhaler, which is due to a small amount of material delivered.
Instructions for use Turbuhaler
Turbuhaler – multi-dose inhaler, which allows dose and inhale the drug in very small doses. When inhaling the powder from the Turbuhaler delivered to the lungs. therefore important that the patient is wide and deep breathed through a mouthpiece.
Before first use, Turbuhaler must be prepared to work:
1. Unscrew and remove the cap.
2. Keep the inhaler upright red feeder bottom. Do not keep the inhaler in the mouthpiece during the rotation of dispenser. Rotate the spout until it stops in one direction, and then also the way – in the opposite direction. Perform the above procedure twice.
Now, the inhaler is ready to 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 procedure:
1. Unscrew and remove the cap.
2. Keep the inhaler upright red feeder bottom. Do not keep the inhaler in the mouthpiece during the rotation of dispenser. In order to measure out the dose, dosing turn to lock in one direction, and then also the way – in the opposite direction.
3. Exhale. Do not exhale through the mouthpiece.
4. Carefully place the mouthpiece between your teeth, your lips and inhale very deeply through your mouth. The mouthpiece does not chew and do not compress your teeth.
5. Before you breathe out, take the inhaler out of his mouth.
6. If you want to inhalation of more than one dose, repeat the paragraphs. 2-5.
7. Close the inhaler cap, check to cover the inhaler was thoroughly screwed.
8. Rinse mouth with water without swallowing.
Do not remove the mouthpiece, because he is fixed on an inhaler and not withdrawn. Turbuhaler mouthpiece rotates, but do not turn it unnecessarily.
Since the amount of inhaled powder is very small, we can not get a taste of the powder after inhalation.
However, absolutely accurate compliance manual provides inhalation (ingalirovanie) of the required dosage.
If, before taking this medication 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. In this case, the indicator will show the total number of dose-measured doses.
Sound that is heard when shaking the inhaler, is a drying agent, and not drugs.
Need to replace the inhaler
The indicator shows the approximate number of doses of doses remaining in the inhaler, the count of doses to fill the Turbuhaler begins with the 60 th or 120 th dose (depending on the total number of doses purchased Turbuhaler). The indicator shows the range of 10 doses, so it does not show each metered (loaded) dose.
Turbuhaler delivers the correct dose of the drug, even if no noticeable change in the indicator window of doses.
The appearance of a red background in the dose indicator window means that the Turbuhaler remaining 10 doses of the drug. When you see the number 0 on a red background in the middle of the window dose inhaler should be discarded.
It is worth noting that even when the indicator window shows the number 0, metering continues to turn. However, the dose indicator stops to fix the number of doses (ceases to move) and the window dose inhaler remains the number 0.
Cleaning
Regularly (1 time per week), the mouthpiece should be cleaned out with a dry cloth. Do not use water or other liquids to clean the mouthpiece.
Utilization
Use caution when handling used an inhaler and to remember that inside the inhaler may be a certain amount of the drug.
Side effect Symbicort Inhaler
On the background of the joint appointment of the two drugs were noted to increase the incidence of adverse reactions.
The most common adverse reactions associated with drug intake, are such pharmacologically expected to beta2-agonists unwanted side effects as tremors and tachycardia, which usually have a moderate degree of intensity and disappear in 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 placebo group (p> 0.001 and p> 0.01, respectively).
CNS: frequent (> 1 / 100, but 1 / 1000, but 1 / 100, but 1 / 1000, but 1 / 10 000 but < 1 / 1000) – atrial fibrillation, supraventricular tachycardia, extrasystoles, very rare ( 1 / 100, but 1 / 1000, but 1 / 100, but 1 / 10 000 but 1 / 1000, but 1 / 10 000 but 1 / 10 000 but Systemic effects of inhaled corticosteroids may occur while taking the drug at high doses for a long time.
The use of beta2-agonists may lead to an increase in the blood levels of insulin, free fatty acids, glycerol, ketone derivatives.
Contraindications Symbicort Inhaler
- Children up to age 6 years;
- Hypersensitivity to budesonide, formoterol or inhaled lactose.
Caution should be used Symbicort Turbuhaler in patients with pulmonary tuberculosis (active or inactive form), fungal, viral or bacterial infections of the respiratory system in patients with hyperthyroidism, pheochromocytoma, diabetes mellitus, uncontrolled hypokalemia, idiopathic hypertrophic subaortalnym stenosis, severe hypertension, aneurysm of any location or other serious cardiovascular diseases (CHD, tachyarrhythmia or heart failure, severe), with lengthening of the interval QT (formoterol may cause QTc prolongation).
Application of pregnancy and breastfeeding
No clinical data on the use of Symbicort Turbuhaler, or a combination of formoterol and budesonide during pregnancy.
Symbicort Turbuhaler during pregnancy should be prescribed only in cases where the expected benefits of therapy to the mother justifies the potential risk to the fetus. Budesonide should be used in the lowest effective dose needed to maintain adequate control of asthma symptoms.
It is not known whether formoterol stand and budesonide in breast milk in humans. Symbicort Turbuhaler can be assigned to breastfeeding women if the expected benefits of therapy to the mother justifies the potential risk to the child.
Use in hepatic dysfunction
No data on the use of Symbicort Turbuhaler patients with liver failure. Since 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 clearance rate of the drug.
Use in renal impairment
No data on the use of Symbicort Turbuhaler patients with renal insufficiency.
Cautions
Recommended to gradually reduce the dose before discontinuation of treatment and is not recommended to abruptly stop therapy.
Symbicort Turbuhaler (80/4.5 mg / dose) is not intended to treat patients with severe bronchial asthma.
Symbicort Turbuhaler is not intended for the initial selection of therapy in the early stages of treatment of bronchial asthma.
With the lack of efficacy or exceeding the recommended dose Symbicort Turbuhaler should be revised treatment strategy. 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, you should consider the possibility of increasing doses of corticosteroids, that is e. designation course of oral corticosteroids or antibiotics in case of accession of infection.
Patients are advised to always carry emergency medications, or Symbicort Turbuhaler (for patients with asthma using Symbicort T urbuhaler for maintenance therapy and cupping), beta2-adrenoceptor agonists short-acting (for all patients using Symbicort Turbuhaler for maintenance therapy).
Should pay attention to the patient’s need for regular admission maintenance dose Symbicort Turbuhaler in accordance with the chosen therapy, even in the absence of symptoms. Inhalation Symbicort Turbuhaler for cupping should be performed only when the symptoms, but the use of the drug is not indicated for routine prophylactic use, ie before exercise. In such cases, demonstrates the use of a separate short-acting bronchodilator.
Treatment Symbicort Turbuhaler should not begin during the exacerbation of asthma.
As with any other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in 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 can occur when taking any inhaled corticosteroids, especially when taking high doses of drugs over a long period of time. Manifestation of systemic effects are less likely during inhalation therapy than with oral corticosteroids. Possible systemic effects include adrenal suppression, growth retardation in children and adolescents, decreased bone mineral density, cataract and glaucoma.
Advised to regularly monitor the growth of children receiving long-term inhaled corticosteroids. In case of growth retardation should be reviewed therapy to reduce the dose of inhaled corticosteroids. Must 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 limited evidence from studies of chronic administration of corticosteroids, we can assume that most children and adolescents receiving inhaled budesonide ultimately achieve normal adult growth rates. However, the reported small (about 1 cm), short-term growth retardation, mainly in the first year of treatment.
Because of the potentially possible action of inhaled corticosteroids 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. Issledovaniya dlitelnogo primeneniya inhaled budesonida u children in the mean dose of 400 micrograms ili adult mean daily dose 800 mcg не showed marked deystviya on bone mineral density. No data on the effect of high doses of the drug on bone mineral density.
If there is reason to believe that against the background of previous systemic treatment with corticosteroids was disturbed adrenal function, precautions should be taken when transferring patients to treatment Symbicort Turbuhaler.
Benefits of budesonide inhalation therapy, usually to minimize the need of oral corticosteroids, but patients who stop treatment with oral corticosteroids for a long time can be saved adrenal insufficiency. Patients who in the past needed to be urgently taking high doses of corticosteroids 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 it is necessary to provide adequate treatment for the SCS. Depending on the degree of violation of adrenal function may require specialist advice before carrying out the recommended procedures.
Should review the need and dose inhaled corticosteroids in patients with active or inactive pulmonary tuberculosis, fungal, viral or bacterial infections of the respiratory system.
Should observe special precautionary measures in patients with unstable asthma, applying a short-acting bronchodilators, for removal of attacks n ri exacerbation of severe asthma, as 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 at a dose of 90 mcg for 3 hours is safe. During the period of treatment should be monitored blood glucose concentration in patients with diabetes mellitus.
Symbicort Turbuhaler contains lactose (less than 1 mg / dose). Usually, this amount does not cause problems in patients with lactose intolerance.
Use in pediatrics
Symbicort Turbuhaler is not recommended for use in COPD in children younger than 6 years.
Symbicort Turbuhaler 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 does not affect the ability to drive vehicles and management mechanisms. May influence the ability to drive vehicles and management mechanisms in the development of side effects.
Overdose Symbicort Inhaler
Symptoms: with an overdose of formoterol – tremor, headache, tachycardia, and in some cases – hyperglycemia, hypokalemia, prolongation QTc, arrhythmia, nausea, and vomiting.
In acute overdose of budesonide, even in large doses, is not expected to clinically significant symptoms. In chronic receiving budesonide in excessive doses can manifest a systemic effect of corticosteroids, such as hypercortisolism and adrenal suppression.
In acute airflow obstruction receiving formoterol at a dose of 90 mcg for 3 hours was safe.
Treatment: supportive and shown symptomatic treatment.
In case you need to cancel Symbicort Turbuhaler as a result of an overdose of formoterol, the incoming and the composition of a combined preparation should consider the appointment of the relevant SSC.
Drug Interactions Symbicort Inhaler
With the simultaneous ingestion of ketoconazole 200 mg 1 time / day and budesonide at a dose of 3 mg budesonide concentration in plasma increased by an average of 6 times. When you have received ketoconazole at 12 h after administration of budesonide in plasma concentration of the latter increased on average by 3 times. Information about such interactions with budesonide inhalation administration is missing, but should expect a significant increase in the concentration of the drug in blood plasma. Since there is currently no data for recommendations on the selection of dose, avoid this combination of drugs. If this is impossible, then the intervals between doses of budesonide and ketoconazole should be maximized. You should also consider lowering the dose of budesonide. Other potent inhibitors of CYP3A4, probably, can also significantly increase the content of budesonide in plasma. Not recommended the appointment of Symbicort Turbuhaler as maintenance therapy and cupping the patients receiving potent inhibitors of CYP3A4.
Β-adrenergic blockers can weaken or inhibit the action of formoterol. Symbicort Turbuhaler should not be administered concurrently with beta-blockers (including eye drops), except in cases of extreme necessity.
With the simultaneous application of Symbicort Turbuhaler and quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors and tricyclic antidepressants may QT prolongation and increased risk of ventricular arrhythmias.
In addition, levodopa, levothyroxine, oxytocin, and ethanol can reduce the tolerance of the heart muscle by beta2-adrenomimetikami.
When concomitant administration of MAO inhibitors and drugs with similar properties (furazolidone, procarbazine), may increase blood pressure.
During anesthesia drugs halogenated hydrocarbons during treatment with Symbicort Turbuhaler there is an increased risk of arrhythmias in patients.
At the same time taking Symbicort Turbuhaler and other β-adrenergic agonists may increase the side effects of formoterol.
Gipokaliemicheskoe effect of beta2-agonists may be enhanced by concomitant administration of xanthine derivatives, mineral derivatives of the SCS and diuretics. Hypokalaemia increases the predisposition to develop arrhythmias in patients receiving cardiac glycosides.
There was no interaction of budesonide with other drugs used to treat asthma.
