Composition, form of production and packaging
The tablets covered with a cover of dark brown color, oval, biconcave, with risk, on one side of the risk are engraved "MJ", on the other - "RPN"; On a cross section - reddish-brown color with white impregnations.
isoniazid 60 mg
rifampicin 120 mg
pyrazinamide 300 mg
ethambutol hydrochloride 225 mg
pyridoxine hydrochloride 20 mg
Excipients: corn starch, microcrystalline cellulose, croscarmellose sodium, silicon dioxide colloid, sodium starch glycolate, talc, magnesium stearate, opadrai brown 04B56936.
500 pcs. - Polymer containers.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
Isocomb is a five-component preparation containing a fixed amount of isoniazid, rifampicin, pyrazinamide, ethambutol and pyridoxine hydrochloride.
Isoniazid has a bactericidal effect on the actively dividing cells of Mycobacterium tuberculosis. The mechanism of its action is the inhibition of the synthesis of mycolic acids, which are a component of the cell wall of mycobacteria. For Mycobacterium tuberculosis, the minimum inhibitory concentration (MIC) is 0.025-0.05 mg / L. Isoniazid has a moderate effect on slow and fast-growing atypical mycobacteria.
The mechanism of action of rifampicin is the inhibition of DNA-dependent RNA polymerase. With tuberculosis infection, rifampicin has a bactericidal effect on the intracellular and extracellularly located microorganisms. For mycobacteria tuberculosis MIC for rifampicin is 2 mg / l.
The pyrazinamide target is the synthetase gene 1 of the mycobacterial fatty acid involved in the biosynthesis of mycolic acid. It acts on intracellularly located mycobacteria, it penetrates well into the centers of tuberculous lesion. More effective in an acidic environment.
The intake of isoniazid in together with the preparations that make up Isocomb does not affect the rate of its absorption from the gastrointestinal tract (GI tract).Penetrates isoniazid in many tissues and fluids, including spinal fluid (CSF). The time to reach the maximum concentration of the drug in the blood (C max ) is 2 hours, the maximum concentration is -6.6 mg / l, the half-life is 5.8 hours. The high C max level of maximum concentration and half-life (T 1/2 ) is explained by the slowing down of isoniazid excretion under the influence of pyrazinamide. Isoniazid practically does not bind to plasma proteins.
Isoniazid up to 80-90% is excreted in urine and 10% with feces during the day. The main products of isoniazid metabolism are N-acetylisoiniazide and isonicotinic acid.
After taking Isocomb in healthy adults, the maximum concentration of rifampicin in plasma reaches 16.3 mg / l. When taking the drug with food, the absorption of rifampicin is reduced by 30%. C max rifampicin is achieved in 1.5-2 hours, T 1/2 is about 6 hours. 3 times less is associated with plasma proteins rifampicin. which is part of Isocomb. About 30% of the drug is excreted in the urine. Rifampicin is metabolized in the liver. The main metabolite is deacetyltripham. Weight metabolites of rifampicin have antimicrobial activity against mycobacterium tuberculosis (MBT).
After taking Isocomba C max, pyrazinamide in plasma reaches 24.1 mg / L after 3 hours. T 1/2 of the drug is an average of 17 hours. The main active metabolite is pyrazinamide pyrazinic acid. Up to 70% metabolites of pyrazinamide are excreted in urine and about 4% - unchanged drug.
After taking Isomocomb C max, ethambutol is 6.4-7.6 mg / l. High C max ethambutol is explained by the slowing of its excretion under the influence of isoniazid. C max of the drug in plasma (60%) is achieved after 2 hours.
Etambutol is excreted in urine 70% unchanged in 30% as aldehyde and carboxyl inactive metabolites. On average, 25% of the drug binds to proteins; plasma.
Absorbed rapidly throughout the small intestine, a larger amount is absorbed in the jejunum.
Metabolised in the liver with the formation of pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxal phosphate with plasma proteins binds to 90%. Well penetrate into all tissues; accumulate mainly in the liver, less - in the muscles and the central nervous system. Penetrates through the placenta, is secreted with breast milk. T 1/2 -15-20 days. It is excreted by the kidneys.
- for the first time diagnosed various forms and localization of tuberculosis, with the presence or absence of bacterial excretion (MW sensitive to the main antituberculous drugs).
For adults and children from the age of 13, the drug is dosed according to rifampicin 10 mg / kg body weight, but not more than 5 tab. The drug is taken on an empty stomach for 30-40 minutes before breakfast. The course of treatment is from 2 to 4 months, depending on the nature of the tuberculosis process.
With a body weight> 80 kg additionally prescribed isoniazid in the evening (total daily dose of isoniazid - 10 mg / kg). According to the indications, Isocomb is combined with streptomycin (IM / dose 15 mg / kg 1 time / day).
From the side of the central nervous system and peripheral nervous system: headache, dizziness, rarely unusual fatigability or weakness, irritability, euphoria, insomnia, paresthesia, numbness of limbs, peripheral neuropathy, optic neuritis, polyneuritis, psychosis, mood change, depression. Seizures can occur in patients with epilepsy.
From the cardiovascular system: palpitation, angina pectoris, increased blood pressure.
On the part of the digestive system: nausea, vomiting, gastralgia, toxic hepatitis.
Allergic reactions: skin rash, itching, hyperthermia, arthralgia.
Other: very rarely - gynecomastia, menorrhagia, tendency to bleeding and hemorrhage.
On the part of the digestive system: nausea, vomiting, diarrhea, decreased appetite, erosive gastritis, pseudomembranous enterocolitis; increased activity of hepatic transaminases in the blood serum, hyperbilirubinemia, hepatitis.
Allergic reactions: urticaria, eosinophilia, angioedema, bronchospasm, arthralgia, fever.
From the side of the central nervous system: headache, reduced visual acuity, ataxia, disorientation.
From the urinary system: nephronecrosis, interstitial nephritis.
Other: leukopenia, dysmenorrhea, induction of porphyria, myasthenia gravis, hyperuricemia, exacerbation of gout.
With an irregular reception or with the resumption of treatment after the break, an influenza-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.
On the part of the digestive system: nausea, vomiting, diarrhea, metallic taste in ptu, impaired liver function (decreased appetite, liver tenderness, hepatomegaly, jaundice, yellow atrophy of the liver): exacerbation of peptic ulcer.
From the side of the central nervous system: dizziness, headache, sleep disturbances, increased excitability, depression; in some cases - hallucinations, convulsions, confusion.
On the part of the hematopoiesis and hemostasis system: 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.
From the side of the nervous system and sensory organs: weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the limbs, numbness, paresis, itching), optic neuritis (decreased visual acuity, mainly - green and red colors, color blindness, scotoma).
On the part of the digestive system: decreased appetite, nausea, vomiting, gastralgia, impaired liver function - increased activity of hepatic transaminases.
Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.
Other: hyperuricemia, exacerbation of gout.
Allergic reactions, hypersecretion of hydrochloric acid, numbness, the appearance of a feeling of compression in the limbs - a symptom of "stocking" and "gloves", rarely - a skin rash, itching of the skin.
Treatment of patients with a multicomponent drug reduces the medical burden on the patient by 3 times, which contributes to the improvement of drug tolerance.
- hypersensitivity to isoniazid, rifampicin, pyrazinamide, ethambutol, pyridoxine;
- Pregnancy and breastfeeding;
- children's age till 13 years;
- liver and GI diseases in acute phase;
- CNS diseases (epilepsy and other diseases with a tendency to convulsive seizures);
- Diseases of the organs of vision (inflammation of the optic nerve, cataracts, diabetic retinopathy, inflammatory diseases of the eyes);
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and during breastfeeding.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in liver diseases.
APPLICATION FOR CHILDREN
The drug is contraindicated for children under 13 years.
The intake of isoniazid, rifampicin, ethambutol, and especially pyrazinamide in a combined dosage form significantly increases antimicrobial activity against MBT.Rifampicin induces certain enzymes of the cytochrome P450 system, accelerating the metabolism of prednisolone, phenytoin, quinidine, oral anticoagulants, hormonal contraceptives, antifungals, cimetidine, cyclosporine A.
Isoniazid reduces the association of rifampicin with plasma proteins, pyrazinamide slows the excretion of rifampicin.
Para-aminosalicylic acid (PASC) impairs the absorption of rifampicin.
The use of rifampicin with lomefloxacin and ofloxacin leads to a decrease in the antimicrobial activity of these combinations in relation to MBT.
Antacids, opioid analgesics reduce the bioavailability of rifampicin.
MAO inhibitors increase the risk of side effects from the central nervous system, cardiovascular system.
Pyridoxine, glutamic acid reduces the risk of developing side effects of isoniazid.
The combined use of isoniazid and cycloserine increases the risk of developing neurotoxic side effects.
Pyrazipamid increases the concentration of isoniazid and rifampicin in the serum, slowing their excretion. When taking rifampicin together with pyrazinamide, the risk of developing hepatotoxic reactions increases.
Aluminum hydroxide reduces the absorption of ethambutol.
The use of ethambutol with aminoglycosides, ciprofloxacin, imipenem, carbamazepine, lithium salts, quinine increases the risk of neurotoxic action of the drug.
Etambutol enhances the antimicrobial activity of other antituberculosis drugs.
Pyridoxine hydrochloride weakens the action of levodopa when administered together. Pyridoxine hydrochloride reduces the risk of developing toxic effects of anti-tuberculosis drugs on the central nervous system and peripheral nervous system.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. In a dry, dark place, out of reach of children, at a temperature of no higher than 25 В° C.
Shelf life - 2 years. Do not use after the expiration date indicated on the package.