Kombipek

General characteristics. Structure:

Active ingredients: 200 mg of theophylline of anhydrous and 6 mg, 8 mg or 10 mg of salbutamol of a gemisuktsinat in 1 tablet. 

Excipients: composition polymeric carrier (the polymethacrylic acid and polyethyleneglycol (macrogoal) interpolimerny complex), calcium stearate (calcium stearate).

Pharmacological properties:

Pharmacodynamics. Kombipek has the pharmacological properties inherent in theophylline and salbutamol. Theophylline belongs to phosphodiesterase inhibitors, increases accumulation in tsAMF fabrics that reduces sokratitelny activity of smooth muscles. Theophylline expands bronchial tubes, blood vessels (mainly, vessels of a brain, skin and kidneys). Reduces pulmonary vascular resistance, reduces pressure in a small circle of blood circulation. Has a promoting effect on a respiratory center, increases the frequency and force of cordial reductions, a renal blood stream. Has moderately expressed diuretic effect. Oppresses aggregation of thrombocytes.

Salbutamol is the selection (32-adrenomimetiky. Renders the expressed broncholitic effect, the bronchospasm warns; reduces resistance in respiratory tracts, increases the vital capacity of lungs; prevents allocation of a histamine and factors of a chemotaxis of neutrophils.

On the pharmakodinamichesky effects Kombipek is drug with slow release of theophylline and salbutamol therefore drug is not appointed for stopping of medical emergencies.

Bronkhodilatiruyushchy action of Kombipek develops gradually in 30 minutes, is expressed is shown in 3-6 h after reception. Active components of drug are released from a polymeric matrix is dosed at the expense of what their constant concentration in blood during 10-12 h are provided, and the lasting clinical effect is reached in several days of treatment. Effective concentration of theophylline in blood is within a day maintained by administration of drug 2 times a day.

Kombipek's appointment results in additivity or potentiation of bronchodilatory effect of theophylline and salbutamol as in a week the maximum increase in indicators of FVD with considerable decrease in bronchial resistance is noted.

Pharmacokinetics. At single use of tablets Kombipek processes of absorption and removal of active agents proceed slowly:

The maximum concentration both theophylline, and salbutamol in blood is defined by 3-9 h and reaches the level 4,07± 0,24 of mkg/ml for theophylline and 6,58±0,49 ng/ml for salbutamol. The period of semi-absorption makes 1,38±0,79 h for theophylline and 1,43±0,63 h for salbutamol, and an elimination half-life - 11,7±8,3 h and 7,15±2,55 h respectively. The average time of keeping of active agents makes 19±11,4 h for theophylline and 12,7±3,2 h for salbutamol.

However the maximum concentration of theophylline and salbutamol in blood serum of patients does not reach that level which, according to literary data, corresponds to therapeutic.

At repeated use of tablets value of equilibrium concentration for theophylline made 6,67±1,17 mkg/ml; for salbutamol - 4,25±0,591 ng/ml.

Absolute bioavailability of theophylline in tablets Kombipek makes 56,6%. The volume of distribution of theophylline of 0,536±0,124 l, salbutamol - 11,6±2,3 l.

Theophylline is exposed to a biotrasformation in a liver with formation of inactive metabolites. It is excreted generally by kidneys, partially allocated with breast milk. In not changed look at adults 10% of theophylline are removed.

Salbutamol is exposed to a biotrasformation in a liver. It is removed with urine and bile, it is preferential in not changed look (90%) or in the form of a glucuronide.

Indications to use:

Treatment and prevention of reversible obstruction of respiratory tracts at bronchial asthma (including night attacks of bronchial asthma), chronic obstructive bronchitis, emphysema slight and other diseases of the respiratory organs which is followed by emergence of a bronchospasm.

Route of administration and doses:

Kombipek accept inside after food, washing down with water. The tablet cannot be crushed, chewed and dissolved in water. The adult appoint on 1 tablet 2 times a day.

The maximum daily dose of theophylline should not exceed 12-14 mg on body weight kg, but no more than 1,2 g. The maximum daily dose of salbutamol makes 32 mg.

Optimum doses of salbutamol and duration of use of drug are selected the doctor individually taking into account a clinical picture of bronchial obstruction and body weight of the patient (since the minimum dose of salbutamol), individual portability of drug, associated diseases, a concomitant use of other medicines. Duration of treatment averages 1-3 months. At good tolerance and efficiency longer term of purpose of drug is possible.

Features of use:

At pregnancy use is contraindicated. In the period of a lactation for the period of treatment by drug feeding by a breast is stopped.

Efficiency of effect of theophylline can decrease at smokers.

To be careful at the use of large numbers of kofeinsoderzhashchy products or drinks during treatment.

Taking into account a profile of side effects it is not recommended to manage at administration of drug vehicles and to be engaged in other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Kombipek is not intended for stopping of medical emergencies. Treatment by the prolonged forms is carried out at periodic control of concentration of theophylline to blood.

Medicines of the prolonged action substantially reduce probability of emergence of dozozavisimy side effect.

Side effects:

At Kombipek's use manifestation of the following side effects is possible.

From a nervous system, dizziness, headache, sleeplessness, nervous tension, excitement, uneasiness, irritability, spasms, tremor.

From cardiovascular system: a heart consciousness, tachycardia, arrhythmia, a cardialgia, premature ventricular contraction, a lowering of arterial pressure (ABP), a collapse, myocardium ischemia, increase in frequency of attacks of stenocardia, feeling of "inflows" of blood to face skin.

From respiratory system: tachypnea, fluid lungs.

From the alimentary system, heavy feeling in a stomach, a gastralgia, nausea, vomiting, dryness in a mouth, a gastroesophageal reflux, heartburn, an aggravation of a peptic ulcer, diarrhea, at long reception - a loss of appetite.

Allergic reactions: skin rash, itch, Quincke's disease.

Laboratory indicators: an albuminuria, a hamaturia, a hyperglycemia, increase in concentration in blood of free fatty acids, a hypopotassemia.

Others: the increased sweating.

Side effects decrease at a dose decline of drug or pass independently at continuation of treatment within 2-3 first weeks of therapy.

In literature side effect of the monodrugs which are Kombipek's part (theophylline and salbutamol) in case of their overdose is described: allergic reactions (urticaria, erethomatous rashes, Quincke's disease), ischuria, psychoneurological disturbances, including psychomotor excitement, tremor of fingers, confusion of consciousness, uneasiness, hallucinations, photophobia, spasms.

The combined drug of the prolonged action Kombipek favourably differs from monodrugs as, in view of slow release of active agents, multidirectional action on some indicators (for example, an ischuria salbutamol and diuretic effect of theophylline), the undesirable side reactions inherent to monodrugs are substantially leveled.

Interaction with other medicines:

Theophylline increases probability of development of side effects of glucocorticosteroids, mineralkortikosteroid (hypernatremia), means for the general anesthesia (the risk of developing of ventricular arrhythmias increases), the means exciting the central nervous system (increases a neurotoxicity).

Antidiarrheal drugs and enterosorbents reduce theophylline absorption.

Rifampicin, phenobarbital, Phenytoinum, isoniazid, carbamazepine, Sulfinpyrazonum, аминоглутетимид, oral estrogensoderzhashchy contraceptives and морацизин, being inductors of microsomal enzymes of a liver, increase clearance of theophylline that can demand increase in its dose.

At simultaneous use with inhibitors of P 450 cytochrome antibiotics of group of macroleads, lincomycin, Allopyrinolum, Cimetidinum, izoprenaliny, enoksatsiny, small doses of ethanol, Disulfiramum, ftorkhinolona, recombinant interferon alpha, a methotrexate, meksiletiny, propafenony, thiabendazole, tiklopidiny, verapamil and at vaccination against flu intensity of effect of theophylline can increase that can demand decrease in its dose.

Theophylline strengthens effect of beta-adrenergic agonists and diuretics (including due to increase in glomerular filtering), reduces efficiency of drugs of lithium and beta adrenoblockers.

Theophylline is compatible to spasmolysants, do not apply together with other derivatives of xanthine, with care appoint along with anticoagulants.

Salbutamol strengthens action of stimulators of the central nervous system, a kardiotropnost of hormones of a thyroid gland.

Salbutamol increases probability of glikozidny intoxication, reduces efficiency of hypotensive drugs, nitrates.

Xanthines at simultaneous use with salbutamol increase probability of development of tachyarrhythmias; means for inhalation anesthesia, a levodopa - heavy ventricular arrhythmias.

Monoamine oxidase inhibitors and tricyclic antidepressants, strengthening effect of salbutamol, can lead to sharp decrease in the ABP.

Salbutamol is incompatible with non-selective beta adrenoblockers.

Simultaneous use of salbutamol with anticholinergics (including inhalation) can promote increase in intraocular pressure.

Diuretics and glucocorticosteroids strengthen gipokaliyemichesky effect of salbutamol.

Contraindications:

Hypersensitivity to theophylline (including to other derivatives of xanthine - to caffeine, a pentoksifillin, theobromine) and to salbutamol, an acute myocardial infarction, unstable stenocardia, a tachyarrhythmia, premature ventricular contraction, coronary heart disease, chronic heart failure, myocarditis, heart diseases, including an aortal stenosis, a pheochromocytoma, glaucoma, piloroduodenalny narrowing, a liver or renal failure, a fluid lungs, sepsis, a gastroesophageal reflux, gastrointestinal bleeding in the recent anamnesis, heavy arterial hyper - or hypotension, widespread atherosclerosis of vessels, a hemorrhagic stroke, an eye retinal apoplexy, a thyrotoxicosis, a dekompensirovanny diabetes mellitus, epilepsy, the increased convulsive activity, a peptic ulcer of a stomach and duodenum in aggravation stages, pregnancy, children's age (up to 16 years).

With care it is necessary to apply at a peptic ulcer of a stomach and duodenum (in the anamnesis), an uncontrollable hypothyroidism (a possibility of cumulation), a long hyperthermia, a prostate hyperplasia, at advanced age.

Overdose:

Symptoms. Symptoms: a gastralgia, diarrhea, nausea, vomiting (including with blood), gastrointestinal bleeding, a tachypnea, a dermahemia of the person, tachycardia, ventricular arrhythmias, a headache, hallucinations, sleeplessness, motive excitement, uneasiness, a photophobia, a tremor, spasms. At a serious poisoning epileptoidny attacks (especially at children aged from 16 up to 18 years without emergence of any harbingers), a hypoxia, a metabolic acidosis, a hyperglycemia, a hypopotassemia, decrease in the ABP, a necrosis of skeletal muscles, confusion of consciousness, a renal failure with a myoglobinuria can develop.

Treatment. drug withdrawal, a gastric lavage, reception of absorbent carbon, laxative medicines, an enteroclysis a combination of polyethyleneglycol and electrolytes, an artificial diuresis, hemosorption, a plazmosorbtion, a hemodialysis (efficiency is not high, peritoneal dialysis is not effective), symptomatic therapy by cardioselective beta adrenoblockers at tachycardia. When developing spasms to maintain passability of respiratory tracts and to carry out an oxygenotherapy. For stopping of spasms - in/in diazepam, 0,1-0,3 mg/kg (but no more than 10 mg). At severe nausea and vomiting - Metoclopramidum or ондансетрон (intravenously).

Storage conditions:

In dry, protected from light, the place, unavailable to children, at a temperature not above +25 °C. A period of validity - 5 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action of 6 mg +200 mg, 8 mg +200 mg, 10 mg +200 mg. On 10 tablets in a blister strip packaging or on 50 tablets in banks plastic. 5 blister strip packagings or each can together with the application instruction place in a pack from a cardboard.