Composition, form of production and packaging
Tablets 1 tab.
pyrazinamide 600 mg
protionamide 25 mg
rifabutin 75 mg
pyridoxine 15 mg
100 pieces. - polymer cans (1) - packs of cardboard.
500 pcs. - polymer cans (1) - packs of cardboard.
1000 pcs. - polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Antituberculous combined agent.
Pyrazinamide
Anti-tuberculosis, antibacterial drug. It acts on intracellularly located microbacteria, it penetrates well into the centers of tubercular lesion. Its activity does not decrease in the acidic environment of caseous masses, in connection with which, it is prescribed for caseo-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 microbacteria (including atypical bacteria), on outside 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 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
Quickly and completely absorbed in the gastrointestinal tract. In plasma, it binds to proteins by 10-20%. C max 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 unchanged form - 3%, in the form of pyrazinic acid - 33%, in the form of other metabolites - 36%.
Prothionamide
In the gastrointestinal tract absorbed quickly. C max in 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 during meningitis). Metabolised in the liver (one of the metabolites - sulfoxide, has tuberculostatic activity). It is excreted by the kidneys and with bile (15-20% unchanged).
The use of rifabutin and protionamide in combination is due to the pronounced synergistic effect.
Rifabutin
Quickly absorbed from the gastrointestinal tract. C max 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 up to 30 hours after administration. Rifabutin penetrates well into the cells of various organs and tissues, penetrates the blood-brain barrier (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 multiple drug-resistant Mycobacterium tuberculosis (with established sensitivity to the components of the drug);
- chronic multidrug-resistant tuberculosis;
- in empirical regimens, 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 HIV infection.
DOSING MODE
Adults inside, after eating 3-4 tablets a day once. In case of poor tolerance, daily intake of 2-3 doses is acceptable.
SIDE EFFECT
Side effects in the treatment with the drug Protubutin plus are determined by the active ingredients that make up its composition:
Pyrazinamide
On the part of the digestive system: nausea, vomiting, diarrhea, "metallic" taste in the mouth, impaired liver function (decreased appetite, pain in the right upper quadrant, hepatomegaly, jaundice, yellow atrophy of the liver), exacerbation of peptic ulcer.
From the nervous system: dizziness, headache, sleep disorders, 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 side of the urinary system: dysuria, interstitial nephritis.
Allergic reactions: skin rash, hives.
Other: hyperthermia, acne, hyperuricemia, exacerbation of gout, photosensitivity, increased serum iron concentration.
Prothionamide
On the part of 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
On the part of the gastrointestinal tract, liver: nausea, vomiting, taste change (dysgeusia), diarrhea, abdominal pain, increased activity of "liver" transaminases, jaundice.
From the hematopoiesis: 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 feeling of compression of the extremities - the symptoms of "stockings" and "gloves", rarely - rash, itching of the skin.
CONTRAINDICATIONS
- hypersensitivity to the components of the drug and to rifampicin;
acute gastritis;
- Stomach ulcer and duodenal ulcer;
- erosive-ulcerative colitis;
acute hepatitis;
- cirrhosis of the liver;
- Hyperuricemia;
- gout;
- cardiac ischemia;
- deficiency of lactase;
lactose intolerance;
- glucose-galactose malabsorption;
- Pregnancy;
- lactation period;
- childhood.
With caution: diabetes mellitus, severe hepatic / renal failure.
PREGNANCY AND LACTATION
It is forbidden to use this drug during pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Take with caution in severe kidney failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in acute hepatitis, cirrhosis. Take with caution in severe hepatic insufficiency.
APPLICATION FOR CHILDREN
Contraindicated in childhood.
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 take into account the possibility of cross-resistance and not prescribe the drug with resistance established in ethionamide. Oral contraceptives may be ineffective, other contraceptive methods should be used.
During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.
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, IV short-acting barbiturates, pyridoxine, osmotic diuretics, sodium bicarbonate in the development of metabolic acidosis.
DRUG INTERACTION
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 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
It reduces the effect 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 systems. Pyridoxine does not affect the antimicrobial activity of the antituberculous drugs that make up the drug.
TERMS OF RELEASE FROM PHARMACY
For hospitals.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life - 2 years.
Do not use after the expiration date printed on the package.
