Isocomb® (Isocomb®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceIsoniazid + Pyrazinamide + Rifampicin + Etambutol + PyridoxineIsoniazid + Pyrazinamide + Rifampicin + Etambutol + Pyridoxine
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  • Isocomb®
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    AKRIKHIN HFK, JSC     Russia
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    • Dosage form: & nbsp
    coated tablets
    Composition:

    1 tablet contains

    active substances:

    isoniazid - 60 mg,

    rifampicin -120 mg,

    pyrazinamide 300 mg,

    ethambutol hydrochloride -225 mg,

    pyridoxine hydrochloride 20 mg

    and Excipients: corn starch, microcrystalline cellulose, croscarmellose sodium, silicon dioxide colloid, sodium starch glycolate, talc, magnesium stearate, opadrai brown 04B56936.

    Description:The tablets covered with a film cover, dark brown color, the oval form, biconcave. On the cross-section the tablet is reddish-brown in color with white patches.
    Pharmacotherapeutic group:Anti-tuberculosis combination drug
    ATX: & nbsp

    J.04.A.M.06   Isoniazid in combination with pyrazinamide, rifampicin and ethambutol

    Pharmacodynamics:

    Isocomb is a five-component preparation containing a fixed amount of isoniazid, rifampicin, pyrazinamide, ethambutol and pyridoxine hydrochloride.

    Isoniazid has a bactericidal effect on actively dividing cells 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 mycobacteria 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.

    Rifampicin

    The mechanism of action of rifampicin is the inhibition of DNA-dependent RNA polymerase. With tuberculosis infection rifampicin has a bactericidal effect on intracellular and extracellularly located microorganisms. For mycobacteria tuberculosis MIC for rifampicin is 2 mg / l.

    Pyrazinamide

    The pyrazinamide target is the mycobacterial fatty acid synthase 1 gene, which is 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. To demonstrate the bactericidal activity of pyrazinamide, the drug is exposed in the body, the enzymatic conversion into the active form - pyrazinic acid. When acid pH values ​​of MIC pyrazinamide in vitro is 20 mg / l.

    Ethambutol

    Etambutol is a bacteriostatic drug that is effective against mycobacteria tuberculosis, resistant to other anti-TB drugs. The MIC of ethambutol is - 0,78-2,0 mg / l.

    Etambutol suppresses the synthesis of the cell wall, blocking the inclusion of mycolic acids in it. Ethambutol Active against rapidly and slowly growing atypical mycobacteria.

    Pyridoxine hydrochloride

    Vitamin product. Participates in the metabolism. It is necessary for the normal functioning of the central and peripheral nervous system. When treating antituberculous drugs, a pyridoxine deficiency may occur. In this regard, the daily dose of vitamin increases to 60 mg. With the simultaneous administration of pyridoxine inwards with isoniazid, rifampicin, pyrazinamide and ethambutol there is no interaction these drugs on the pharmacokinetic and microbiological levels.

    Pharmacokinetics:

    Isoniazid

    Receiving isoniazid inside with the preparations that are part of Isocomb®, does not affect on the rate of its absorption from the gastrointestinal tract (GIT). Penetrates isoniazid in many tissues and fluids, including spinal fluid (CSF).Time to reach the maximum concentration of the drug in the blood (Cmax) - 2 hours, the maximum concentration is -6,6 mg / l. the elimination half-life is 5.8 hours. Tall Cmax level of maximum concentration and half-life (T1/2) 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 - N-acetyl isosine and isonicotinic acid.

    Rifampicin

    After receiving 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%. The maximum concentration of rifampicin is reached after 1.5-2 hours, the half-life 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 deacetyltrifampicin. All metabolites of rifampicin have antimicrobial activity against mycobacterium tuberculosis (MBT).

    Pyrazinamide

    After taking Isocomb® Cmax pyrazinamide in plasma reaches 24.1 mg / L after 3 hours. T1/2 the drug is an average of 17 hours. The main active metabolite of pyrazinamide is pyrazinic acid. Up to 70% metabolites of pyrazinamide are excreted in urine and about 4% - unchanged drug.

    Ethambutol

    After taking Isocomb® Cmax ethambutol is 6.4-7.6 mg / l. High Cmax ethambutol is explained by the slowing of its excretion under the influence of isoniazid. Cmax drug in plasma (60%) is achieved after 2 hours.

    Etambutol is excreted in urine 70% unchanged in 30% in the form of aldehyde and carboxyl inactive metabolites. On average, 25% of the drug binds to plasma proteins.

    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 communicates by 90%. Well penetrate into all tissues; accumulate mainly in the liver, less - in the muscles and central nervous system (CNS). Penetrates through the placenta, is secreted with breast milk. T1/2 - 15-20 days. It is excreted by the kidneys.

    Indications:For the first time diagnosed various forms and localizations of tuberculosis,with the presence or absence of bacterial excretion (MBT sensitive to the main anti-tuberculosis drugs).
    Contraindications:

    - When hypersensitivity to isoniazid, rifampicin, pyrazinamide, ethambutol. pyridoxine;

    - pregnancy and breastfeeding;

    - children's age till 13 years;

    - diseases of the liver and gastrointestinal tract in the acute phase;

    - diseases of the central nervous system (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);

    - gout;

    - thrombophlebitis.

    Dosing and Administration:Inside. Adults and children from 13 years. The drug is dosed according to rifampicin 10 mg / kg body weight, no more than 5 tablets. The drug is taken on an empty stomach for 30-40 minutes before breakfast. The total exchange rate is from 2 to 4 months, depending on the nature of the tuberculosis process. With a body weight> 80 kg is additionally prescribed isoniazid in the evening (the total daily dose of isoniazid - 10 mg / kg). According to the indications, Isocomb® is combined with streptomycin (intramuscularly at a dose of 15 mg / kg once a day).
    Side effects:

    Isoniazid

    From the nervous system: headache, dizziness, rarely - unusual fatigue 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 side of the cardiovascular system (CVS): palpitation, stenocardia, increased blood pressure (BP).

    From the digestive system: nausea, vomiting, gastralgia, toxic hepatitis.

    Allergic reactions: skin rash, itching, hyperthermia, arthralgia.

    Other: very rarely - gynecomastia, menorrhagia, a tendency to bleeding and hemorrhage.

    Rifampicin

    From 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 nervous system: headache, decreased 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 a break, there may be an influenza-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure.

    Pyrazinamide

    From the digestive system: nausea, vomiting, diarrhea, "metallic" taste in the mouth, impaired liver function (decreased appetite, liver soreness, 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 organs of hematopoiesis and the system of hemostasis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.

    From the side of the musculoskeletal system: arthralgia, myalgia.

    From the urinary system: dysuria, interstitial nephritis.

    Allergic reactions: skin rash, hives.

    Other: hyperthermia, acne. hyperuricemia, exacerbation of gout, photosensitization, increased serum iron concentrations.

    Ethambutol

    From the nervous system and sense organs: weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the limbs, numbness, paresis, itching), optic neuritis (decreased visual acuity, impaired color perception, mainly green and red colors, color blindness, scotoma).

    From the digestive system: decreased appetite, nausea, vomiting, gastralgia, impaired liver function - increased activity of "liver" transaminases. Allergic reactions: dermatitis, skin rash, itching, arthralgia, fever, anaphylaxis.

    Other: hyperuricemia, exacerbation of gout.

    Pyridoxine hydrochloride

    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.

    Interaction:

    The use of isoniazid, rifampicin, ethambutol, and especially pyrazinamide in a combined dosage form significantly increases antimicrobial activity against MBT. Rifampicin induces some enzymes of the cytochrome P-450 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. Paraaminosalicylic acid (PASK) worsens the absorption of rifampicin. The use of rifampicin with lomefloxacin and ofloxacin leads to a decrease in the antimicrobial activity of these combinations against MBT. Antacids, opioid analgesics reduce the bioavailability of rifampicin

    Isoniazid

    MAO inhibitors increase the risk of side effects from the CNS, CCC. Pyridoxine, glutamic acid reduce the risk of developing side effects of isoniazid. The combined use of isoniazid and cycloserine increases the risk of developing neurotoxic side effects.

    Pyrazinamide

    Pyrazinamide 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.

    Ethambutol

    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. Ethambutol enhances the antimicrobial activity of other antituberculosis drugs.

    Pyridoxine hydrochloride

    Pyridoxine hydrochloride weakens the action of levodopa when administered together. Pyridoxine hydrochloride reduces the risk of developing toxic effects antituberculous drugs on the central and peripheral nervous system.

    Form release / dosage:
    The tablets covered with a cover, 60 mg + 300 mg + 120 mg + 225 mg + 20 mg.
    Packaging:

    For 50 or 100 tablets in a can of polypropylene or in a jar of high pressure polyethylene or low pressure polyethylene.

    Each bank along with the instruction for use is placed in a pack of cardboard.

    25 cans of 100 tablets together with instructions for use are placed in a box of cardboard (for inpatient). For 500 or 1000 tablets per mock of polyethylene film unstabilized.The polyethylene bag, together with the instruction sheet, is placed in a polypropylene container or in a container of high pressure polyethylene or low pressure polyethylene (for inpatient).

    Storage conditions:

    In a dry, the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:2 years. Do not use after the expiration date indicated on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:P N003363 / 01
    Date of registration:14.05.2009 / 13.10.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp23.10.2017
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