Protubutin

General characteristics. Structure:

Active ingredients: 600 mg of Pyrazinamidum, 25 mg of Prothionamidum, 75 mg of a rifabutin, 15 mg of a pyridoxine.

The antituberculous combined remedy which is well getting into the centers of tubercular defeat.

Pharmacological properties:

Pharmacodynamics. Pyrazinamidum. Antitubercular, antibacterial drug. Affects intracellularly located mycobacteria, well gets into the centers of tubercular defeat. Its activity does not decrease in acid medium of caseous masses, in communication with what it is appointed at caseous and necrotic processes, caseous lymphadenites, tuberkuloma. Depending on a dose renders bactericidal or bacteriostatic effect.

Prothionamidum. An antituberculous remedy, on chemical structure it is close to Etioniamidum. Has bacteriostatic action generally on the breeding mycobacteria (including atypical), on out of - and intracellularly located microorganisms. Blocks synthesis of the mikoliyevy acids which are the most important structural component of a cell wall of mycobacteria of tuberculosis, has properties of the antagonist of niacin. In high concentration breaks synthesis of protein of a microbic cell. Secondary stability develops quickly.

Rifabutin. Semi-synthetic antibiotic of a broad spectrum of activity, group of Rifamycinums. It is effective in the relation intracellularly and vnekletochno the located microorganisms. Selectively suppresses a DNA-dependent RNA polymerase of bacteria. Has bactericidal effect. From 5 to 15% of strains of Mycobacterium tuberculosis, resistant to rifampicin, are sensitive to a rifabutin.

Pyridoxine. Plays an important role in a metabolism, it is necessary for normal functioning of a nervous system. In a fosforilirovanny form the pyridoxine is a coenzyme of a large number of the enzymes operating on not oxidizing exchange of amino acids. Participates in exchange of tryptophane, methionine, cysteine, glutaminic, etc. amino acids. Plays an important role in exchange of a histamine. Contributes to normalization of lipidic exchange.

Pharmacokinetics. Pyrazinamidum. It is quickly and completely soaked up in digestive tract. In plasma contacts proteins for 10-20%. The maximum concentration (Cmax) is reached in 1-2 h. Well gets into fabrics and bodies, including through a blood-brain barrier. It is metabolized in a liver, at the same time the intermediate active metabolite having mikobakteriostatichesky activity is formed. Biological half-life makes 8-9 hours. It is removed by kidneys: in not changed look – 3%, in the form of pirazinoyevy acid – 33%, in the form of other metabolites – 36%.

Prothionamidum. In digestive tract it is soaked up quickly. The maximum concentration (Cmax) in plasma is noted in 2-3 hours after intake. Easily gets into bodies and fabrics (tuberculous focuses, cavities in lungs, a serous and purulent pleural exudate, cerebrospinal fluid at meningitis). It is metabolized in a liver (one of metabolites - sulphoxide, has tuberculostatic activity). It is removed by kidneys and with bile (15-20% in not changed look). Use in a combination of a rifabutin and Prothionamidum is caused by the expressed sinergidny action.

Rifabutin. It is quickly soaked up from digestive tract. The maximum concentration (Cmax) reaches approximately in 2-4 hours after intake. Concentration of a rifabutin in plasma is maintained above the minimum inhibiting concentration (MIC) for M. by tuberculosis to 30 h from the moment of reception. Rifabutin well gets in cells of various bodies and fabrics, gets through a blood-brain barrier (concentration in cerebrospinal fluid makes about 50% of concentration in plasma). It is metabolized in a liver with formation of inactive metabolites. It is removed by kidneys in the form of metabolites (53%) and with bile (30%). The elimination half-life makes 35-40 h.

Pyridoxine. It is soaked up quickly throughout a small bowel. It is metabolized in a liver with formation pharmacological of active metabolites. Well gets into all fabrics; collects preferential in a liver, it is less - in muscles and the central nervous system. Gets through a placenta, cosecretes with breast milk. An elimination half-life (T1/2) - 15-20 days. It is removed by kidneys, and also during a hemodialysis.

Indications to use:

Tuberculosis (various forms and localizations), as a part of complex therapy. At patients with multiple medicinal resistance of mycobacteria of tuberculosis (with the established sensitivity to drug components). Chronic polyresistant tuberculosis. In the empirical modes of treatment of sharply progressing tuberculosis at for the first time the revealed patients, with high risk of medicinal stability in an intensive phase of treatment. The tuberculosis associated with HIV infection.

Route of administration and doses:

The adult inside, after food on 3-4 tablets a day once. At bad portability reception of a daily dose in 2-3 receptions is allowed.

Features of use:

At prolonged treatment it is necessary to control number of leukocytes, thrombocytes in peripheral blood, activity of alaninaminotranspherase, aspartate aminotransferase and concentration of uric acid in blood once a month.

At patients with a diabetes mellitus the risk of emergence of a hypoglycemia increases. The risk of development of a uveitis increases at a combination with klaritromitsiny or reception in high doses. At development of a uveitis consultation of the ophthalmologist, temporary drug withdrawal is shown.

Can give reddish-orange color to urine, skin and the cosecreted liquids, contact lenses. It is necessary to consider a possibility of cross stability and not to appoint drug at the established resistance to Etioniamidum.

Oral contraceptives can be inefficient, it is necessary to use other contraceptives.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Side effects at treatment by the drug Protubutin® plus are defined by the active ingredients which are its part.

Pyrazinamidum. From the alimentary system - nausea, vomiting, diarrhea, "metal" smack in a mouth, an abnormal liver function (a loss of appetite, pain in right hypochondrium, a hepatomegalia, jaundice, a yellow hepatatrophia), an aggravation of a round ulcer. From a nervous system: dizziness, a headache, sleep disorders, a hyperexcitability, depressions, in some cases - hallucinations, spasms, confusion of consciousness. From bodies of a hemopoiesis: thrombocytopenia, sideroblastny anemia, vacuolation of erythrocytes, porphyria, hypercoagulation, splenomegaly. From a musculoskeletal system: arthralgia, mialgiya. From an urinary system: dysuria, intersticial nephrite. Allergic reactions: skin rash, small tortoiseshell. Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitization, increase in concentration of serumal iron.

Prothionamidum. So the parties of the alimentary system - nausea, vomiting, diarrhea, hypersalivation, "metal" smack in a mouth, an abnormal liver function. From a nervous system: sleeplessness, excitement, a depression, uneasiness, it is rare – dizziness, drowsiness, a headache, an adynamy, in isolated cases - paresthesias, a peripheral neuropathy, an optic neuritis. From outside warmly - vascular system: tachycardia, weakness, orthostatic hypotension. From endocrine system: a hypoglycemia at patients with a diabetes mellitus, a gynecomastia, a dysmenorrhea, a hypothyroidism, decrease in a potentiality. Allergic reactions: skin rash.

Rifabutin. From outside zheludochno – an intestinal path, a liver: nausea, vomiting, taste change (dysgeusia), diarrhea, abdominal pain, increase in activity of "hepatic" transaminases, jaundice. From system of a hemopoiesis: leukopenia, thrombocytopenia, anemia. From skeletal and muscular system: arthralgia, mialgiya. Allergic reactions: fever, rash, it is rare - an eosinophilia, a bronchospasm, an acute anaphylaxis, a uveitis.

Pyridoxine: allergic reactions, hypersecretion of hydrochloric acid, numbness, emergence of feeling of a prelum of extremities - a symptom of "stockings" and "gloves", it is rare - rash, a skin itch.

Interaction with other medicines:

Pyrazinamidum. Pyrazinamidum increases concentration of an isoniazid and rifampicin in blood serum, slowing down their excretion. At reception of rifampicin together with Pyrazinamidum a hepatotoxic raises. At simultaneous use with the medicines blocking canalicular secretion decrease in their removal and strengthening of toxic reactions is possible. Strengthens antitubercular action of an ofloksatsin and lomefloksatsin.

Prothionamidum. Let's combine with an isoniazid, Pyrazinamidum, Cycloserinum and other antitubercular drugs. The isoniazid increases concentration of Prothionamidum in plasma.

Rifabutin. Accelerates metabolism of medicines (induces CYP3A isoenzymes and by that can influence pharmacokinetics) in a liver that increase in a dose of medicines can demand. Reduces concentration of a zidovudine in plasma. Development of clinically significant interactions with Ethambutolum, theophylline, streptocides, Pyrazinamidum, flukonazoly, zaltsitabiny is improbable. Flukonazol and кларитромицин increase concentration of a rifabutin in plasma. Between rifabutiny and ftorkhinolonam there is an antagonism at the microbic level.

The pyridoxine weakens action of a levodopa at their combined use. Strengthens diuretic effect of diuretics. Pharmaceutical thiamin and cyanocobalamine is not compatible to vitamins. Reduces risk of emergence of toxic impact of antitubercular drugs on the central and peripheral nervous system. The pyridoxine does not influence antimicrobic activity of the antituberculous remedies which are a part of drug.

Contraindications:

Hypersensitivity to components of drug and to rifampicin. Acute gastritis, a peptic ulcer of a stomach and a 12-perstny gut, erosive and ulcer colitis, an acute hepatitis, cirrhosis, a hyperuricemia, gout, coronary heart disease, deficit of lactase, a lactose intolerance, glucose - galaktozny malabsorption, pregnancy, the lactation period, children's age.

With care. Diabetes mellitus, heavy liver/renal failure, hyperuricemia, gout.

Overdose:

Symptoms: fluid lungs, confusion of consciousness, spasm, peripheral neuropathy, abnormal liver function, nausea, vomiting, diarrhea, muffled speech, respiratory depression, stupor, coma. Treatment: gastric lavage, purpose of absorbent carbon; symptomatic therapy, an artificial diuresis, artificial ventilation of the lungs, intravenously – barbiturates of short action, a pyridoxine, osmotic diuretics, sodium bicarbonate at development of a metabolic acidosis.

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated on 100, 500 or 1000 tablets (for hospitals) in bank of polymeric.