Protubutin® (Protubutin®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substancePyrazinamide + Prothionamide + Rifabutin + [Pyridoxine]Pyrazinamide + Prothionamide + Rifabutin + [Pyridoxine]
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  • Protubutin®
    pills inwards 
    FARMASINTEZ, JSC (Irkutsk)     Russia
    • Dosage form: & nbspFilm-coated tablets.
    Composition:

    Composition per one tablet

    Active substances:

    Pyrazinamide 600 mg

    Prothionamide 25 mg

    Rifabutin 75 mg

    Pyridoxine hydrochloride 15 mg

    Excipients:

    Core: lactose monohydrate (sugar milk) - 18.0 mg, povidone (medium-molecular weight polyvinylpyrrolidone, kollidon 25) - 14.0 mg, microcrystalline cellulose -170.0 mg, pregelatinized starch 4.0 mg, sodium carboxymethyl starch (primogel) 40.0 mg magnesium stearate 11.0 mg, magnesium hydrosilicate (talc) 11.0 mg, silicon dioxide colloid (aerosil brand A-3 00) 12.0 mg, crospovidone (collidone CL) 5.0 mg, potato starch (EP) 100.0 mg. Film Sheath: hydroxypropyl methylcellulose 15 hypromellose E 15) 23.0 mg, propylene glycol 2.3 mg, castor oil 0.9 mg, magnesium hydrosilicate (talc) 0.8 mg, titanium dioxide 1.0 mg, ferric oxide red 2.0 mg.

    Description:

    The tablets covered with a film cover, the oval form, biconcave, red - brown color. On the cross section of the tablet is purple with dark purple, white and yellow impregnations.

    Pharmacotherapeutic group:Antituberculous
    ATX: & nbsp

    J.04.A.M   Combinations of antituberculous drugs

    Pharmacodynamics:

    Antituberculous combined agent.

    Pyrazinamide. Anti-tuberculosis, antibacterial drug. It acts on intracellularly located mycobacteria, it penetrates well into the centers of tubercular lesion. Its activity does not decrease in the acidic environment of caseous masses, in connection with what is assigned in caseous-necrotic processes, caseous lymphadenitis, tuberculomas. Depending on the dose, it has a bactericidal or bacteriostatic effect.

    Prothionamide. Anti-tuberculosis means, by chemical structure, is close to ethionamide. It has a bacteriostatic effect mainly on multiplying mycobacteria (including atypical ones), on extra- and intracellularly located microorganisms. It blocks the synthesis of mycolic acids, which are the most important structural component of the cell wall of mycobacterium tuberculosis, has the properties of a nicotinic acid antagonist. In high concentrations, the synthesis of the protein of the microbial cell is disrupted. Secondary resistance develops rapidly.

    Rifabutin. Semisynthetic antibiotic of broad spectrum of action, a group of rifamycins.Effective against intracellular and extracellularly distributed microorganisms. Selectively inhibits the DNA-dependent RNA polymerase of bacteria. Has a bactericidal effect. From 5 to 15% of strains resistant to rifampicin Mycobacterium tuberculosis are sensitive to rifabutin.

    Pyridoxine. It plays an important role in the metabolism, it is necessary for the normal functioning of the nervous system. In the phosphorylated form pyridoxine is a coenzyme of a large number of enzymes acting on a non-oxidative exchange of amino acids. Participates in the exchange of tryptophan, methionine, cysteine, glutamic and other amino acids. It plays an important role in the exchange of histamine. Promotes the normalization of lipid metabolism.

    Pharmacokinetics:

    Pyrazinamide. Quickly and completely absorbed in the gastrointestinal tract. In plasma, it binds to proteins by 10-20%. The maximum concentration (Cmax) is achieved in 1-2 hours. It penetrates well into tissues and organs, including through the blood-brain barrier. Metabolized in the liver, with the formation of an intermediate active metabolite, which has mycobacteriostatic activity. The half-life of the organism is 8-9 hours.It is excreted by the kidneys: in unmodified form - 3%, in the form of pyrazinic acid - 33%, in the form of other metabolites - 36%.

    Prothionamide. In the gastrointestinal tract absorbed quickly. The maximum concentration (Cmax) in the plasma is noted 2-3 hours after ingestion. Easily penetrates into organs and tissues (tubercular foci, caverns in the lungs, serous and purulent pleural effusion, cerebrospinal fluid with meningitis). Metabolised in the liver (one of the metabolites - sulfoxide, has tuberculostatic activity). It is excreted by the kidneys and with bile (15-20 % in unmodified form).

    The use of rifabutin and protionamide in combination is due to the pronounced synergistic effect.

    Rifabutin. Quickly absorbed from the gastrointestinal tract. The maximum concentration (Cmax) reaches approximately 2-4 hours after ingestion. The concentration of rifabutin in the plasma is maintained above the minimum inhibitory concentration (MIC) for M. tuberculosis until 30 hours from the time of admission. Rifabutin penetrates into the cells of various organs and tissues, penetrates the blood-brain barrier (the concentration in the cerebrospinal fluid is about 50% of the concentration in the plasma). Metabolized in the liver with the formation of inactive metabolites.It is excreted by the kidneys in the form of metabolites (53%) and with bile (30%). The half-life is 35-40 hours.

    Pyridoxine. Absorbed rapidly throughout the small intestine. Metabolised in the liver with the formation of pharmacologically active metabolites. It penetrates well into all tissues; accumulates mainly in the liver, less - in the muscles and central nervous system. Penetrates through the placenta, is secreted with breast milk. The half-life (T1 / 2) is 15-20 days. It is excreted by the kidneys, as well as during hemodialysis.

    Indications:

    Tuberculosis (various forms and localizations), as part of complex therapy. In patients with multidrug-resistant mycobacterium tuberculosis (with established sensitivity to the components of the drug). Chronic multidrug-resistant tuberculosis. In the empirical regimes of treatment of acute progressive tuberculosis in newly diagnosed patients, with a high risk of drug resistance in the intensive phase of treatment. Tuberculosis, associated with VRI infection.

    Contraindications:

    Hypersensitivity to the components of the drug and to rifampicin. Acute gastritis, peptic ulcer of stomach and duodenum,erosive and ulcerative colitis, acute hepatitis, liver cirrhosis, hyperuricemia, gout, coronary artery disease, lactase deficiency, lactose intolerance, glucose-galactose malabsorption, pregnancy, lactation, infancy.

    Carefully:

    Diabetes mellitus, severe hepatic / renal failure, hyperuricemia, gout.

    Dosing and Administration:

    Adults inside, after eating 3-4 tablets per day once. In case of poor tolerance, daily intake of 2-3 doses is acceptable.

    Side effects:

    Side effects in the treatment with the drug Protubutin® plus are determined by its active ingredients.

    Pyrazinamide.

    From the digestive system - nausea, vomiting, diarrhea, "metallic" taste in the mouth, abnormal liver function (loss of appetite, pain in the right upper quadrant, hepatomegaly, jaundice, yellow atrophy of the liver), exacerbation of peptic ulcers.

    From the nervous system: dizziness, headache, sleep disturbances, increased excitability, depression, in some cases - hallucinations, convulsions, confusion.

    From the hematopoiesis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.

    From the musculoskeletal system: arthralgia, myalgia.

    From the urinary system: dysuria, interstitial nephritis.

    Allergic reactions: skin rash, hives.

    Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitivity, increased serum iron concentration.

    Prothionamide.

    From the digestive system - nausea, vomiting, diarrhea, hypersalivation, "metallic" taste in the mouth, impaired liver function.

    From the nervous system: insomnia, agitation, depression, anxiety, rarely - dizziness, drowsiness, headache, asthenia, in single cases - paresthesia, peripheral neuropathy, optic neuritis.

    From the cardiovascular system: tachycardia, weakness, orthostatic hypotension. On the part of the endocrine system: hypoglycemia in patients with diabetes mellitus, gynecomastia, dysmenorrhea, hypothyroidism, decreased potency.

    Allergic reactions: skin rash.

    Rifabutin.

    From the gastrointestinal tract, liver: nausea, vomiting, taste change (dysgeusia), diarrhea, abdominal pain, increased activity of "liver" transaminases, jaundice.

    On the part of the hematopoiesis system: leukopenia, thrombocytopenia, anemia.

    From the musculoskeletal system: arthralgia, myalgia.

    Allergic reactions: fever, rash, rarely - eosinophilia, bronchospasm, anaphylactic shock, uveitis.

    Pyridoxine.

    Allergic reactions, hypersecretion of hydrochloric acid, numbness, the appearance of a sense of compression of the limbs - a symptom of "stocking" and "gloves", rarely - a rash, itching of the skin.

    Overdose:

    Symptoms: pulmonary edema, confusion, convulsions, peripheral neuropathy, impaired liver function, nausea, vomiting, diarrhea, slurred speech, respiratory depression, stupor, coma.

    Treatment: gastric lavage, the appointment of activated charcoal; symptomatic therapy, forced diuresis, artificial ventilation, intravenous - barbiturates of short action, pyridoxine, osmotic diuretics, sodium bicarbonate in the development of metabolic acidosis.

    Interaction:

    Pyrazinamide. Pyrazinamide increases the concentration of isoniazid and rifampicin in the serum, slowing their excretion.When taking rifampicin together with pyrazinamide, hepatotoxicity increases. When used simultaneously with drugs that block tubular secretion, it is possible to reduce their excretion and enhance toxic reactions. Strengthens the anti-tuberculosis effect of ofloxacin and lomefloxacin.

    Prothionamide. Compatible with isoniazid, pyrazinamide, cycloserine and other anti-tuberculosis drugs. Isoniazid increases the concentration of protionamide in the plasma.

    Rifabutin. Accelerates the metabolism of drugs (induces isoenzymes CYP3A and thus can affect the pharmacokinetics) in the liver, which may require an increase in the dose of medicines. Reduces the concentration of zidovudine in plasma. It is unlikely to develop clinically significant interactions with ethambutol, theophylline, sulfonamides, pyrazinamide, fluconazole, zalcitabine. Fluconazole and clarithromycin increase the concentration of rifabutin in plasma. Between rifabutin and fluoroquinolones there is antagonism at the microbial level.

    Pyridoxine weakens the action of levodopa when combined. Enhances the diuretic effect of diuretics.Pharmaceutically not compatible with vitamins thiamine and cyanocobalamin. Reduces the risk of toxic effects of antituberculosis drugs on the central and peripheral nervous system. Pyridoxine does not affect the antimicrobial activity of the antituberculous drugs that make up the drug.

    Special instructions:

    With long-term treatment, it is necessary to monitor the number of leukocytes, platelets in peripheral blood, the activity of alanine aminotransferase, aspartate aminotransferase and the concentration of uric acid in the blood once a month. In patients with diabetes, the risk of hypoglycemia increases.

    The risk of uveitis increases with combination with clarithromycin or in high doses. With the development of uveitis, consultation of an ophthalmologist, temporary withdrawal of the drug is indicated. Can give a reddish-orange color of urine, skin and secreted fluids, contact lenses. It is necessary to consider the possibility of cross-resistance and not prescribe the drug with established resistance to ethionamide.

    Oral contraceptives may be ineffective, other contraceptive methods should be used.

    Effect on the ability to drive transp. cf. and fur:

    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Tablets, film-coated 600 mg + 25 mg + 75 mg + 15 mg.

    Packaging:

    Primary packaging of medicinal product. 100, 500 or 1000 tablets (for hospitals) are placed in a polymer jar with a lid tightened with the control of the first opening. Free space is filled with cotton wool. Labels are applied to cans from paper label or writing or from polymeric materials, self-adhesive.

    Secondary packaging of medicinal product. Banks, together with an equal number of instructions for use, are placed in a group package.

    Storage conditions:

    Store in a dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:4 years. Do not use after the expiration date indicated on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008176/10
    Date of registration:17.08.2010
    The owner of the registration certificate:FARMASINTEZ, JSC (Irkutsk) FARMASINTEZ, JSC (Irkutsk) Russia
    Manufacturer: & nbsp
    Information update date: & nbsp30.04.2016
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