Combiback (Combipec)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceSalbutamol + TheophyllineSalbutamol + Theophylline
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  • Combiback
    pills inwards 
    FARMAPEK, ZAO     Russia
    • Dosage form: & nbsp
    sustained-release tablets
    Composition:

    One tablet contains

    active substances: theophylline anhydrous 200 mg and salbutamol hemisuccinate 6 mg or theophylline anhydrous 200 mg and salbutamol hemisuccinate 8 mg or theophylline anhydrous 200 mg and salbutamol hemisuccinate 10 mg.

    Excipients: a composite polymeric carrier (polymethacrylic acid and polyethylene glycol (macrogol) interpolymer complex) 72 mg or 70 mg or 68 mg, respectively; calcium stearate (calcium stearic acid) 2 mg.

    Description:
    Tablets are white, biconvex. A weak specific odor is allowed.
    Pharmacotherapeutic group:Bronchodilator combination
    ATX: & nbsp

    R.03.D.B.04   Theophylline in combination with adrenergic agents

    Pharmacodynamics:

    Kombipek possesses the pharmacological properties inherent in theophylline and salbutamol. Theophylline refers to inhibitors of phosphodiesterase, increases accumulation in the tissues of cAMP, which reduces the contractile activity of smooth muscle. Theophylline expands bronchi, blood vessels (mainly, vessels of the brain, skin and kidneys).Reduces pulmonary vascular resistance, reduces pressure in a small circle of blood circulation. Has a stimulating effect on the respiratory center, increases the frequency and strength of the heartbeats, kidney blood flow. Has a moderate diuretic effect. Inhibits the aggregation of platelets.

    Salbutamol is a selective β2adrenomimetic. Has a pronounced bronchodilator effect, prevents bronchospasm; reduces resistance in the airways, increases the vital capacity of the lungs; prevents the release of histamine and neutrophil chemotactic factors.

    In its pharmacodynamic effects, Kombipack is a drug with slow release of theophylline and salbutamol, so the drug is not prescribed for relief of emergency conditions.

    The bronchodilating effect of KombiPek develops gradually after 30 minutes, it manifests itself in 3-6 hours after administration. The active components of the drug are released from the polymer matrix in a dose-dependent manner, thereby ensuring constant concentrations in the blood for 10-12 hours, and a persistent clinical effect is achieved after several days of treatment.Effective concentration of theophylline in the blood during the day is maintained by taking the drug 2 times a day.

    The purpose of Kombipek leads to additivity or potentiation of the bronchodilating effect of theophylline and salbutamol, since a maximum increase in FVD values ​​with a significant decrease in bronchial resistance is observed in a week.

    Pharmacokinetics:

    With a single use of Kombipek tablets, the processes of absorption and excretion of active substances proceed slowly: the maximum concentration of both theophylline and salbutamol in the blood is determined after 3-9 hours and reaches a level of 4.07 ± 0.24 μg / ml for theophylline and 6.58 ± 0.49 ng / ml for salbutamol. The half-absorption period is 1.38 ± 0.79 h for theophylline and 1.43 ± 0.63 h for salbutamol, and the half-life is 11.7 ± 8.3 h and 7.15 ± 2.55 h, respectively. The average retention time of active substances is 19 ± 11.4 h for theophylline and 12.7 ± 3.2 h for salbutamol.

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

    With repeated use of tablets, the equilibrium concentration for theophylline was 6.67 ± 1.17 μg / ml; for salbutamol - 4.25 ± 0.591 ng / ml.

    Absolute bioavailability of theophylline in Kombipack tablets is 56.6%. The volume of distribution of theophylline is 0.536 ± 0.124 L, salbutamol is 11.6 ± 2.3 L.

    Theophylline undergoes biotransformation in the liver with the formation of inactive metabolites. Excreted mainly by the kidneys, partially excreted in breast milk. In unchanged form in adults, 10% of theophylline is excreted.

    Salbutamol undergoes biotransformation in the liver. It is excreted in urine and bile, mainly in unchanged form (90%) or in the form of glucuronide.

    Indications:Treatment and prevention of reversible airway obstruction in bronchial asthma (including nocturnal attacks of bronchial asthma), chronic obstructive bronchitis, emphysema and other respiratory diseases accompanied by the appearance of bronchospasm.
    Contraindications:Hypersensitivity to theophylline (including other derivatives of xanthine - caffeine, pentoxifylline, theobromine) and salbutamol, acute myocardial infarction,unstable angina, tachyarrhythmia, extrasystole, ischemic heart disease, chronic heart failure, myocarditis, heart defects, including aortic stenosis, pheochromocytoma, glaucoma, pyloroduodenal narrowing, hepatic or renal failure, pulmonary edema, sepsis, gastroesophageal reflux, gastrointestinal bleeding in a recent medical history, severe arterial hyper- or hypotension, widespread atherosclerosis of the blood vessels, hemorrhagic stroke, retinal hemorrhage, thyrotoxicosis, decubitus retired diabetes mellitus, epilepsy, increased convulsive activity, gastric ulcer and duodenal ulcer in the acute stage, pregnancy, children's age (under 16 years).
    Carefully:
    With caution should be used for peptic ulcer of the stomach and duodenum (in the anamnesis), uncontrolled hypothyroidism (the possibility of cumulation), prolonged hyperthermia, prostatic hyperplasia, in old age.
    Pregnancy and lactation:When pregnancy is contraindicated. During lactation during the treatment with the drug, lactation is stopped.
    Dosing and Administration:

    Kombipek taken inside after eating, washed down with water. The tablet can not be grinded, chewed and dissolved in water. Adults appoint 1 tablet 2 times a day.

    The maximum daily dose of theophylline should not exceed 12-14 mg per kg of body weight, but not more than 1.2 grams. The maximum daily dose of salbutamol is 32 mg.

    The optimum doses of salbutamol and the duration of the drug are selected by the doctor individually, taking into account the clinical picture of bronchial obstruction and body weight of the patient (starting from the minimum dose of salbutamol), individual drug tolerance, concomitant diseases, simultaneous administration of other medications. The duration of treatment is an average of 1-3 months. With good tolerability and efficacy, a longer duration of prescription is possible.

    Side effects:

    When using Kombipeka, the following side effects may occur.

    From the nervous system: dizziness, headache, insomnia, nervous tension, agitation, anxiety, irritability, convulsions, tremor.

    From the cardiovascular system: palpitation, tachycardia, arrhythmia, cardialgia, extrasystole, lowering of arterial pressure (BP), collapse, myocardial ischemia, an increase in the frequency of angina attacks, a feeling of "tides" of blood to the skin of the face.

    From the respiratory system: tachypnea, pulmonary edema.

    From the digestive system: a feeling of heaviness in the stomach, gastralgia, nausea, vomiting, dry mouth, gastroesophageal reflux, heartburn, peptic ulcer, diarrhea, long-term depression of appetite.

    Allergic reactions: skin rash, itching, angioedema.

    Laboratory indicators: albuminuria, hematuria, hyperglycemia, increased concentration in the blood of free fatty acids, hypokalemia.

    Other: increased sweating.

    Side effects decrease with a decrease in the dose of the drug or pass on their own during the continuation of treatment during the first 2-3 weeks of therapy.

    In the literature, the side effects of the mono preparations that form Combipec (theophylline and salbutamol) are described in case of their overdose: allergic reactions (urticaria, erythematous rashes, angioedema), urinary retention,psychoneurological disorders, including psychomotor agitation, tremor of fingers, confusion, anxiety, hallucinations, photophobia, convulsions.

    The combination drug of prolonged action Kombipek favorably differs from monopreparations, because, in view of the slow release of active substances, multidirectional action on some indicators (for example, urinary retention with salbutamol and diuretic effect of theophylline), unwanted side reactions characteristic of mono preparations are largely leveled.

    Overdose:

    Symptoms: gastralgia, diarrhea, nausea, vomiting (including with blood), gastrointestinal bleeding, tachypnea, facial skin hyperemia, tachycardia, ventricular arrhythmias, headache, hallucinations, insomnia, motor excitement, anxiety, photophobia, tremor, convulsions. In severe poisoning, epileptic seizures may develop (especially in children aged 16 to 18 without any precursors), hypoxia, metabolic acidosis, hyperglycemia, hypokalemia, decreased blood pressure, necrosis of skeletal muscles, confusion, renal insufficiency with myoglobinuria.

    Treatment: withdrawal of the drug, gastric lavage, intake of activated carbon, laxative drugs, intestinal washing with a combination of polyethylene glycol and electrolytes, forced diuresis, hemosorption, plasmasorption, hemodialysis (efficacy is not high, peritoneal dialysis is not effective), symptomatic therapy with cardioselective beta adrenoblockers in tachycardia. If seizures occur, maintain airway patency and conduct oxygen therapy. For arresting seizures - in / in diazepam, 0.1-0.3 mg / kg (but not more than 10 mg). With severe nausea and vomiting, metoclopramide or ondansetron (intravenously).

    Interaction:

    Theophylline increases the likelihood of side effects of glucocorticosteroids, mineral corticosteroids (hypernatremia), funds for general anesthesia (increases the risk of ventricular arrhythmias), drugs that excite the central nervous system (increases neurotoxicity).

    Antidiarrhoeal drugs and enterosorbents reduce the absorption of theophylline.

    Rifampicin, phenobarbital, phenytoin, isoniazid, carbamazepine, sulfinpyrazone, aminoglutethimide, oral estrogen-containing contraceptives and moracisin, as inducers of microsomal liver enzymes, increase the clearance of theophylline, which may require an increase in its dose.

    When used simultaneously with cytochrome P 450 inhibitors, macrolide antibiotics, lincomycin, allopurinol, cimetidine, isoprenaline, enoxacin, small doses of ethanol, disulfiram, fluoroquinolones, recombinant interferon-alpha, methotrexate, mexiletine, propafenone, thiabendazole, ticlopidine, verapamil and in vaccination against the intensity of theophylline may increase, which may require a reduction in its dose.

    Theophylline increases the effect of beta-adrenomimetics and diuretics (including by increasing glomerular filtration), reduces the effectiveness of lithium and beta-blockers.

    Theophylline is compatible with antispasmodics, do not use together with other xanthine derivatives, with caution prescribed simultaneously with anticoagulants.

    Salbutamol enhances the effect of stimulants of the central nervous system, cardiotropic thyroid hormones.

    Salbutamol increases the likelihood of glycoside intoxication, reduces the effectiveness of antihypertensive drugs, nitrates.

    Xanthines with simultaneous application with salbutamol increase the likelihood of developing tachyarrhythmias; means for inhalation anesthesia, levodopa severe ventricular arrhythmias.

    Monoamine oxidase inhibitors and tricyclics, enhancing the effect of salbutamol, may lead to a sharp decrease in blood pressure.

    Salbutamol is incompatible with nonselective beta-blockers.

    Simultaneous use of salbutamol with anticholinergic agents (including inhalation) can promote increased intraocular pressure.

    Diuretics and glucocorticosteroids increase the hypokalemic effect of salbutamol.

    Special instructions:

    The effectiveness of the action of theophylline may decrease in smokers.

    Be careful when consuming large quantities of caffeine-containing foods or drinks during the treatment period.

    Kombipack is not intended for emergency situations. Treatment with prolonged forms is carried out with periodic monitoring of theophylline concentration in the blood.

    Drugs of prolonged action significantly reduce the likelihood of a dose-dependent side effect.

    Effect on the ability to drive transp. cf. and fur:Given the profile of side effects, it is not recommended when administering the drug to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:
    Long-acting tablets 6 mg + 200 mg, 8 mg + 200 mg, 10 mg + 200 mg.
    Packaging:

    10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil.

    5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

    Storage conditions:
    In a dry place, protected from light, out of reach of children, at a temperature not exceeding + 25 ° С.
    Shelf life:
    5 years. Do not use after the date shown on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-000354
    Date of registration:22.02.2011 / 01.03.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:FARMAPEK, ZAO FARMAPEK, ZAO Russia
    Manufacturer: & nbsp
    Information update date: & nbsp31.01.2018
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