Active substanceIsoniazid + Pyrazinamide + Rifampicin + Etambutol + PyridoxineIsoniazid + Pyrazinamide + Rifampicin + Etambutol + Pyridoxine
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    VALENTA PHARM, PAO     Russia
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  • Dosage form: & nbspfilm-coated tablets
    Composition:

    One tablet contains:

    active substances:

    isoniazid 0.075 g;

    pyrazinamide 0.4 g;

    pyridoxine hydrochloride - 0.02 g;

    rifampicin 0.15 g;

    ethambutol hydrochloride 0.275 g.

    Excipients: magnesium stearate, povidone (Kollidon 90F), potato starch, microcrystalline cellulose, croscarmellose;

    Opadrai II (series 85): polyvinyl alcohol, talc, macrogol, titanium dioxide, iron oxide red, aluminum varnish based on the dye sunset yellow sun, aluminum lacquer based on ponso 4R; giprolose (Klucel), copovidone (Kollidon VA-64).

    Description:Tablets covered with a shell of red-brown color, capsular form. On the cross-section, two layers are visible, the inner layer is brownish-orange in color with dark brown patches.
    Pharmacotherapeutic group:Anti-tuberculosis drug combined
    ATX: & nbsp

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

    Pharmacodynamics:

    Laslonvita® is a five-component preparation containing a fixed amount of isoniazid, rifampicin, pyrazinamide, ethambutol hydrochloride 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 the mycobacterium. For mycobacteria tuberculosis, the minimum inhibitory concentration is 0.025-0.05 mg / l. Isoniazid has a moderate effect on slowly and rapidly growing atypical mycobacteria. The microbiological activity of isoniazid in combination with rifampicin is increased by a factor of 1.5.

    Pyrazinamide

    Pyrazinamide has a bactericidal action at acidic pH values. To manifest the bactericidal activity of pyrazinamide, the preparation is subjected to enzymatic conversion into the active form - pyrazinic acid. At acidic pH values ​​of pyrazinamide MIC in vitro, is 20 mg / l.

    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, the minimum inhibitory concentration (MIC) for rifampicin is 2 mg / L. The anti-tuberculosis activity of pyrazinamide in combination with rifampicin and isoniazid increases more than 2-fold.

    Ethambutol hydrochloride

    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. Microthe biological activity of ethambutol in combination with isoniazid increased by 2 times.

    Pyridoxine hydrochloride

    Vitamin product. Participates in the metabolism. It is necessary for the normal functioning of the central and peripheral nervous systems. With tuberculosis infection, there is a deficiency of pyridoxine.In this regard, the daily dose of vitamin increases to 60-80 mg. With the simultaneous administration of pyridoxine inwards with isoniazid, rifampicin, pyrazinamide and ethambutol, no interaction of these drugs is observed at the pharmacokinetic and microbiological levels.

    Pharmacokinetics:

    Isoniazid

    Taking isoniazid in together with the drugs that make up Laslonvita® does not affect the rate of its absorption from the gastrointestinal tract .. It penetrates isoniazid in many tissues and fluids, including cerebrospinal fluid. The time to reach the maximum concentration in blood plasma is 2 hours, the maximum concentration level is 6.6 mg / l, the half-life period (T1 / 2) is 5.8 hours. A high level of maximum concentration and half-life is due to 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 taking Laslonvita® in healthy adults, the peak concentration of rifampicin in plasma reaches 16.3 mg / l.. At reception of a preparation together with food absorption of rifampicin decreases on 30%. The maximum level of rifampicin is reached after 1.5-2 hours, the half-life is 6.1 hours. 3 times less is associated with plasma proteins rifampicin, which is part of Laslonvite®. About 30% of the drug is excreted in the urine. Rifampicin it is metabolized in Czechenia. The main metabolite is deacetyltrifampicin. All metabolites of rifampicin have antimicrobial activity against mycobacterium tuberculosis.

    Pyrazinamide

    After taking Laslonvite®, the maximum concentration of pyrazinamide in plasma reaches 24.13 mg / L after 3 hours. The half-life of the drug is an average of 17 hours. The main active metabolite of pyrazinamide -: pyrazinic acid, up to 70% excreted urine metabolites of pyrazinamide and 3.4% - unchanged drug.

    Ethambutol hydrochloride

    After taking Laslonvite®, the maximum concentration of ethambutol in plasma corresponds to 6.4-7.6 mg / l. A high level of the maximum concentration of ethambutol is explained by the slowing of its excretion under the influence of isoniazid. The peak concentration of the drug in plasma in 60% occurs after 2 hours, in 30% - after 3,4,6 hours. Ethambutol excreted in urine in 70% in unchanged form and in 30% in the form of aldehyde and carboxyl inactive metabolites. Average 25% The drug binds to plasma proteins.

    Pyridoxine hydrochloride

    After taking Laslosinvita®, it is absorbed rapidly throughout the small intestine, a larger amount is absorbed in the jejunum. Metabolized in the liver with the formation of pharmacologically active metabolites (pyridoxalphosphate and pyridoxamino phosphate). Pyridoxalphosphate with plasma proteins is 90% related. 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. T1 / 2 - 15-20 days. It is excreted by the kidneys (with intravenous injection - with bile 2%), as well as during hemodialysis.

    Indications:The drug is used for chemotherapy for newly diagnosed patients with respiratory tuberculosis and extrapulmonary forms of tuberculosis, with the presence or absence of bacterial excretion, without drug resistance to the drugs that make up the drug.
    Contraindications:

    - Hypersensitivity to isoniazid, rifampicin, pyrazinamide,ethambutol, pyridoxine;

    - mental illness;

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

    - diseases of the central nervous system (epilepsy and other diseases with a tendency to convulsive seizures);

    - the presence of drug or alcohol dependence;

    - severe renal insufficiency;

    - diseases of the organs of vision;

    - children's age till 18 years.

    Carefully:
    Decompensated diseases of the cardiovascular system (chronic heart failure, angina pectoris, arterial hypertension), hypothyroidism, hyperuriccemia, gout.
    Pregnancy and lactation:
    The drug is contraindicated in pregnancy, during treatment it is necessary to stop breastfeeding.
    Dosing and Administration:

    When dosing Laslonvita® are guided by rifampicin (0.45 g per day for one dose, with a body weight of over 70 kg, it is possible to administer 0.6 g for two doses), but not more than 4 tablets per day.

    Tablets (do not divide, do not grind, do not dissolve in water, do not dissolve and do not chew) take inside.

    Laslonvita® is taken once every 1-2 hours after lunch. The tablets are washed down with water.In case of side effects, the medication should be divided into 2 times.

    If necessary, the patient may be prescribed intramuscularly streptomycin 1.0 or kanamycin 1.0 g.

    According to the testimony, Laslonvita® 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 excessive 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 cardiovascular system:

    palpitation, angina, increased blood pressure.

    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 the break, an influenza-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.

    Pyrazinamide

    From the digestive system:

    nausea, vomiting, diarrhea, "metallic" taste in the mouth, impaired liver function (decreased appetite, liver tenderness, hepatomegaly, jaundice, yellow atrophy of the liver); exacerbation of peptic ulcer.

    From 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 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.

    Ethambutol

    From the nervous system and sensory organs:

    weakness, headache, dizziness, impaired consciousness, disorientation, hallucinations, depression, peripheral neuritis (paresthesia in the limbs, numbness, paresis, pruritus), optic neuritis (decreased visual acuity, violation of color perception, mainly green and red, 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

    Rare: skin rash, itching of the skin.

    Treatment of patients with a multicomponent drug reduces the patient's medical burden by 3 times, which contributes to the improvement of drug tolerance.

    Overdose:

    Isoniazid

    Symptoms: dizziness, dysarthria, lethargy, disorientation, hyperreflexia, peripheral polyneuropathy, abnormal liver function, metabolic acidosis, hyperglycemia, glucosuria, ketonuria, seizures (1-3 hours after drug administration), coma.

    Treatment: peripheral poly neuropathy i (Vitamins B6, Bl, B12, ATP, glutamic acid, nicotinamide, massage, physiotherapy procedures); convulsions (intramuscularly vitamin B6-200-250 mg, iv 40% dextrose-20 ml, w / m 25% magnesium sulfate-10 m solutionl, diazepam); abnormal liver function (methionine, lipid, ATP, Vitamin B 12).

    Pyrazinamide

    Symptoms: a violation of liver function, an increase in the severity of side effects from the central nervous system. Treatment: symptomatic.

    Ethambutol

    Symptoms: nausea, vomiting, hallucinations, polyneuritis.

    Treatment: symptomatic

    Rifampicin

    Symptoms: Pulmonary edema, lethargy, confusion, convulsions

    Treatment: symptomatic; gastric lavage, the appointment of activated charcoal.

    Forced diuresis.

    Pyridoxine

    Symptoms: a circulatory disorder in the extremities, sometimes causes allergic reactions

    Treatment: symptomatic

    Interaction:

    The use of isoniazid, rifampicin, ethambutol and, especially, pyrazinamide in a combined dosage form significantly increases antimicrobial activity against MBT (Mycobacterium tuberculosis).

    Rifampicin induces certain enzymes of the cytochrome P-450 system, accelerating the metabolism of prednisolone, phenytoin, quinidine, oral anticoagulants, contraceptives, antifungals, cimetidine, cyclosporine. Isoniazid reduces the association of rifampicin with plasma proteins, pyrazinamide slows the excretion of rifampicin,

    PASK impairs the absorption of rifampicin. Taking rifampicin with lomefloxacin and ofloxacin results in a decrease in the antimicrobial activity of these combinations against MBT (mycobacterium tuberculosis).

    Antacids, opiates reduce the bioavailability of rifampicin

    Isoniazid

    MAO inhibitors (monoamine oxidase) increase the risk of side effects from the central nervous system, cardiovascular system. Vitamin B6, 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 decreases 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 antimicrobial activity of antituberculosis drugs.

    Pyridoxine

    Pyridoxine weakens the action of levodopa when combined with their use. Pyridoxine protects the central and peripheral nervous system from the toxic effects of anti-tuberculosis drugs.

    Special instructions:

    During the treatment it is necessary to refrain from taking ethanol.With prolonged therapy, it is necessary to regularly monitor the general blood test and liver function parameters. Laboratory indicators - ALT, ACT, serum bilirubin concentration can transiently increase without clinical manifestations. When there are signs of toxic hepatitis the drug is canceled.

    At the beginning of treatment, it is possible to increase cough, increase the amount of sputum. Patients with gout attacks in history, periodically monitor the concentration of uric acid in the serum.

    Form release / dosage:
    Film-coated tablets.
    Packaging:

    For 10 tablets in a contour mesh box made of polyvinyl chloride film, and aluminum foil printed lacquered.

    For 60 tablets in cans of polymer complete with lids.

    Each jar or 10 contour mesh packages together with the instructions for use are placed in a bundle.

    For 36 contour mesh packages are placed in a group package with application instructions in an amount equal to the number of packages (for hospitals).

    Storage conditions:List B. Store in 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.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-006082/08
    Date of registration:31.07.2008 / 24.12.2008
    Expiration Date:Unlimited
    The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia
    Manufacturer: & nbsp
    Information update date: & nbsp12.03.2018
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