Тевакомб

General characteristics. Structure:

Active agents: салметерол (in the form of a salmeterol of a ksinafoat) - 0,025 mg / a dose (for dosages: 25/50 mkg / dose, 25/125 mkg / dose, 25/250 mkg / dose); a flutikazona propionate - 0,050 mg / a dose, 0,125 mg / a dose, 0,250 mg / a dose (for dosages: 25/50 mkg / dose, 25/125 mkg / dose, 25/250 mkg / dose respectively)
Excipients: ethanol, lecithin, тетрафторэтан.

DESCRIPTION: The white homogeneous suspension in the liquefied propellant placed in an aerosol can under pressure.

Pharmacological properties:

Pharmacodynamics. TEVAKOMB represents the combined medicine which part two active components are: флутиказон and салметерол. These medicinal substances belong to various classes (the synthetic fluorinated glucocorticosteroid and the selection agonist of beta2-adrenoceptors of long action) and possess various mechanisms of action.

Flutikazon - the synthetic glucocorticosteroid for topical administration having the expressed antiinflammatory and antiallergic activity. Pharmacological action of a flutikazon is caused by ability to contact glucocorticoid receptors of target cells, including epithelial cells of respiratory tracts. To receptors флутиказон surpasses in affinity degree by 18 times dexamethasone, almost twice beclomethasone-17-monopropionate, an active metabolite of beclomethasone of Dipropionas, and almost three times будесонид. Flutikazon inhibits inflow of mast cells, eosinophils, lymphocytes, macrophages, neutrophils, reduces products and release of mediators of an inflammation and other biologically active agents (including a histamine, prostaglandins, leukotrienes and cytokines) involved in formation allergen - a specific sensitization. As a result permeability of capillaries decreases, exudation disappears, slime secretion by mucous glands decreases, passability of a bronchial tree is recovered. Salmeterol represents the selection agonist of beta2-adrenoceptors of long action. Salmeterol increases the intracellular content of cyclic 3,5-adenosine-monophosphate (tsAMF) that leads to a relaxation of smooth muscles of a wall of bronchial tubes.

The molecule of a salmeterol has a long side chain which contacts the outside domain of a receptor thanks to what салметерол provides protection against the bronkhokonstriktion induced by a histamine and longer bronkhodilatation (duration not less than 12 h) in comparison with agonists of beta2-adrenoceptors of short action. Salmeterol at least by 50 times more селективен to beta2-to adrenoceptors, than salbutamol.

Suppresses an early and late stage of allergic reaction; after introduction of a single dose hyperreactivity of bronchial tubes decreases, suppression of a late stage lasts 30 h when the bronchodilatory effect is already absent.

The described properties demonstrate to what салметерол in addition to broncholitic effect possesses additional action which clinical importance is finally not established.

Salmeterol prevents emergence of a bronchospasm, reduces resistance of respiratory tracts, increases the vital capacity of lungs. In therapeutic doses has no effect on cardiovascular system.

Pharmacokinetics. At joint inhalation introduction флутиказон and салметерол do not influence pharmacokinetics of each other.

Salmeterol is absorbed by tissues of lungs and, without being exposed to metabolism in lungs, gets to a system blood stream. The maximum concentration of a salmeterol in plasma is extremely low (about 200 pg/ml), is reached in 5-10 minutes after administration of drug. Concentration of a salmeterol in plasma correlates with a dose of the inhalated drug.

System absorption флутиказон happens preferential through lungs, and in the beginning absorption happens more intensively, but then is slowed down. A part of an inhalation dose can be swallowed; owing to low solubility of drug in water and in view of his presistemny metabolism, bioavailability makes less than 1% of digestive tract.

Absolute bioavailability флутиказон at use of a salmeterola/flutikazon makes 5,3% of a nominal dose. The maximum concentration in a blood plasma is reached approximately in 0,33-1,5 hours. There is a direct dependence between the size of the inhalated dose and concentration of a flutikazon in a blood plasma.

Distribution of a flutikazon is characterized by bystry clearance from plasma, the large volume of distribution in an equilibrium state (300 l) and a final elimination half-life (T1/2), equal about 5,9 hours. Linkng with proteins of plasma makes about 91%.

Flutikazon is exposed to biotransformation in a liver with the participation of an isoenzyme of CYP3A4 of system of P450 cytochrome with formation of an inactive carboxyl metabolite. It is removed by intestines and with urine, it is preferential in the form of a hydroxylated metabolite. Renal clearance of not changed flutikazon less than 072%, renal clearance of the metabolite containing carboxyl group, less than 5% of a dose.

Indications to use:

Drug TEVAKOMB is shown as basic therapy of bronchial asthma when use of a combination of a beta2-adrenomimetik of the selection long action with an inhalation glucocorticosteroid, and also for a maintenance therapy is reasonable at the chronic obstructive pulmonary disease (COPD).

Route of administration and doses:

Drug TEVAKOMB is intended for inhalations.

Bronchial asthma
Adults and teenagers are more senior than 12 years:
Drug TEVAKOMB of 25 mkg / 50 mkg: 2 inhalation doses 2 times a day.
Drug TEVAKOMB of 25 mkg / 125 mkg: 2 inhalation doses 2 times a day.
Drug TEVAKOMB of 25 mkg / 250 mkg: 2 inhalation doses 2 times a day.

Children from 4 to 12 years:
Drug TEVAKOMB of 25 mkg / 50 mkg: 2 inhalation doses 2 times a day.

Chronic Obstructive Pulmonary Disease (COPD)
Drug TEVAKOMB of 25 mkg / 125 mkg: 2 inhalation doses 2 times a day.
Drug TEVAKOMB of 25 mkg / 250 mkg: 2 inhalation doses 2 times a day.

Drug is appointed in minimum effective dose providing control of symptoms of a disease. At achievement of effect by drug use a dose it is reasonable to lower 2 times a day to minimum effective or to pass to a smaller dosage, frequency rate of use - 1 time a day. The quantity of a flutikazon in the chosen form has to correspond to disease severity.

For obtaining optimum effect drug is used regularly, even in the absence of symptoms of bronchial asthma and HOBL. The doctor establishes a course of treatment and a dose of drug individually.

Patients of advanced age have no need for dose adjustment and at patients with pathology of a liver or kidneys.

Features of use:

Patients have to be informed that for the best effect drug TEVAKOMB needs to be used daily even in the absence of symptoms.

Drug TEVAKOMB is not drug for stopping of attacks of bronchial asthma. Short-range bronchodilators are applied to stopping of attacks. It is always necessary to recommend to the patient to have at itself drug for stopping of a bronchospasm. Increase in need for use of bronchodilators of .korotky action demonstrates deterioration in a course of a disease. The sudden and amplifying deterioration in control of a bronkhospastichesky syndrome poses a potential threat of life. In such situation it is necessary to see a doctor since the used dose of drug TEVAKOMB does not provide adequate control of a disease.

As well as it is necessary to use other inhalation drugs containing GKS, drug TEVAKOMB with care at patients with an active or latent pulmonary tuberculosis, the expressed cardiovascular diseases, including disturbances of a cordial rhythm, a hypopotassemia, a thyrotoxicosis.

Any inhalation GKS can cause system effects, especially at long use in high doses; it should be noted, however, that the probability of emergence of such symptoms is much lower, than at treatment by peroral GKS. Possible system effects include oppression of function of adrenal glands, a growth inhibition at children and teenagers, decrease in mineral density of a bone tissue, a cataract and glaucoma. Considering told, the dose of inhalation GKS should be titrated to minimum which provides maintenance of effective control.

Influence on ability to manage vehicles and other mechanisms
There is no need for special precautionary measures for the persons driving the car or a difficult technique.

Instructions for use inhaler:
Drug TEVAKOMB is placed in an aluminum cylinder with the dosing valve supplied with the inhalation device with a protective cap.
1. Remove a protective cap from the inhalation device and be convinced that an output tube of the inhalation device pure. You keep the inhalation device between index and big fingers in vertical position, at the same time the thumb has to be located on a bottom of the inhalation device, and an index finger on a bottom of an aluminum cylinder.
2. Stir up an aluminum cylinder up-down.
3. Make a deep exhalation through a mouth. Densely clamp an output tube of the inhalation device.
4. Make a slow and deep breath. At the time of a breath press an index finger a bottom of an aluminum cylinder, releasing a drug TEVAKOMB dose, continue to inhale slowly.
5. Remove the inhalation device from a mouth and hold the breath for 10 seconds or for that time which will not cause in you discomfort. Slowly exhale.
6. After inhalation rinse a mouth water, trying not to swallow of an aerosol which got to inhalation time for a mucous membrane of an oral cavity.
7. If it is required to enter more than one dose of drug, wait 1 minute and repeat all actions, since the 2nd step, finishing with a step 6.
8. Close the inhalation device a protective cap.

When performing steps 3 and 4 you do not hurry. At the time of release of a dose of medicine it is important to take a breath as it is possible more slowly. Before use be trained about a mirror. If you noticed "steam" which is coming out a top of a barrel or mouth corners, then start over again from a step 2.

Cleaning of an inhaler
The inhalation device should be cleaned, at least, weekly. Take an aluminum cylinder from the inhalation device. Accurately rinse the inhalation device and a protective cap warm water. It is impossible to use hot water! Stir up the inhalation device and a protective cap to remove the remains of water and dry up them without use of heating devices. It is impossible to lower an aluminum cylinder in water!

Side effects:

As drug TEVAKOMB contains салметерол and флутиказон, it is necessary to expect development of the side reactions characteristic of each component separately. Additional side effects at simultaneous use of two components of drug are noted.

From cardiovascular system: tachycardia, heartbeat, disturbances of a heart rhythm, myocardium ischemia.
From a nervous system: headaches, including migrenozny, frustration of a dream, a tremor, behavioural frustration, including hyperreactivity and irritability, uneasiness.
From immune system: hypersensitivity reactions, including rash and a Quincke's disease, in isolated cases a Quincke's disease of the person and a stomatopharynx, development of respiratory symptoms - an asthma and a bronchospasm and, extremely seldom, anaphylactic reactions, allergic rhinitis and conjunctivitis.
From a respiratory organs: nasal bleedings, nose congestion, dryness of mucous membranes of a nasal cavity, laryngitis, hoarseness of a voice.
From digestive tract: irritation of mucous membranes of a stomatopharynx, change of flavoring feelings, a hypoptyalism, digestive tract infections, defeat of solid tissues of teeth, abdominal pains, the increased gas generation, locks, hemorrhoids.
From integuments: hemorrhages, eczema, dermatitis and dermatosis.

From a musculoskeletal system: spasms in muscles, an ostealgia and joints.
Infections and invasions: candidiasis of a mucous membrane of an oral cavity and throat, infection of urinary tract, respiratory infections, other bacterial and viral infections.

As well as at use of other inhalation drugs, against the background of use of drug TEVAKOMB development of a paradoxical bronchospasm is possible. In this case it is necessary to stop immediately drug use, to estimate a condition of the patient and if it is necessary, to appoint alternative therapy.

Development of the system reactions including Itsenko-Cushing's syndrome, oppression of function of adrenal glands, a growth inhibition at children and teenagers, decrease in mineral density of a bone tissue, a cataract, glaucoma, a hyperglycemia is theoretically possible.

Interaction with other medicines:

In usual conditions after inhalation use of drug low concentration of a salmeterol and flutikazon in a blood plasma are reached, however, potential interaction with other substrates or inhibitors of an isoenzyme CYP3A4 cannot be excluded.

It is necessary to avoid Use of non-selective and selection beta adrenoblockers for patients with bronchial asthma because of danger of development of a bronchospasm. Use of drug TEVAKOMB together with beta adrenoblockers is admissible only in the presence of strict indications.

The combined use with other means containing agonists beta2-adrenoceptors can lead to strengthening of effects.

Contraindications:

Hypersensitivity to a salmeterol, a flutikazon and other components of drug; children's age up to 4 years.

With care: tuberculosis, fungal, viral or bacterial infections, a pheochromocytoma, a thyrotoxicosis, a hypothyroidism, a diabetes mellitus, an uncontrollable hypopotassemia, uncontrollable arterial hypertension, arrhythmias, coronary heart disease, lengthening of an interval of QT on the electrocardiogram, an idiopathic hypertrophic subaortal stenosis, a cataract, glaucoma, osteoporosis, pregnancy, the lactation period.

PREGNANCY AND LACTATION
Pregnant women and the feeding women can appoint drug only if the estimated advantage for mother exceeds potential risk for a fruit or the child.

Overdose:

In case of overdose of drug TEVAKOMB the tremor, a headache, tachycardia are possible. As optimum antidotes apply cardioselective blockers of beta adrenoceptors which should be applied with care when performing treatment of patients with a bronchospasm in the anamnesis. If treatment by drug TEVAKOMB needs to be cancelled in connection with overdose of the beta2-agonist which is a part of drug it is necessary to appoint to the patient the corresponding replacement therapy of GKS.

At prolonged use of drug in the doses exceeding recommended perhaps some oppression of function of bark of adrenal glands. Considering possible complications, it is recommended to carry out monitoring of reserve function of bark of adrenal glands.

Storage conditions:

At a temperature not above 30 °C. Not to freeze. To store in the place, unavailable to children! Period of validity 
3 years. Not to use after the period of validity specified on packaging!

Issue conditions:

According to the recipe

Packaging:

Aerosol for inhalations dosed 25/50 mkg / a dose, 25/125 mkg / a dose, 25/250 mkg / a dose. On 120 doses in the aluminum cylinder with the dosing valve supplied with the inhalation device with a protective cap. On 1 cylinder together with the application instruction in a cardboard pack.