Isozid Comp. (Isozid comp.)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Dosage form: & nbspcoated tablets
Composition:

One tablet contains

Active substances: isoniazid 300 mg, pyridoxine hydrochloride 60 mg

Excipients: core: microcrystalline cellulose 30.00 mg, macrogol 6000 6.00 mg, copolyvidone 12.00 mg, crospovidone 6.00 mg, talc 4.00 mg, calcium hydrophosphate 2.00 mg, shell: hydroxypropylmethylcellulose (hypromellose) 3.40 mg, titanium dioxide E171 1.80 mg, macrogol 6000 1.80 mg.

Description:White round biconvex covered with a film sheath, tablets with a risk for a fault on one side and stamp "300" on the other.
Pharmacotherapeutic group:Anti-tuberculosis combination drug
ATX: & nbsp
  • Isoniazid in combination with other drugs
    • Pharmacodynamics:

    Isozid Comp. Combined drug, which includes an antituberculous agent isoniazid and pyridoxine (vitamin B6).

    Pharmacodynamics

    Isoniazid acts bactericidal, inhibits the synthesis of mycolic acids, which are an important component of the cell wall of mycobacteria. It is especially active against rapidly multiplying microorganisms (including those located intracellularly).

    Pyridoxine plays an important role in the metabolism, it is necessary for the normal functioning of the central and peripheral nervous system. In the phosphorylene form pyridoxine is a coenzyme of a large number of enzymes acting on a non-oxidative exchange of amino acids. It plays an important role in the exchange of histamine. Promotes the normalization of lipid metabolism.

    Pharmacokinetics:

    Isoniazid quickly and completely absorbed when ingested, food reduces absorption and bioavailability. The bioavailability indicator is large the effect has the effect of first passing through the liver. The maximum concentration in the blood is reached after 1 to 2 hours, the maximum concentration in the blood after ingestion of a single dose of 300 mg is 3-7, μg / ml. The connection with proteins is insignificant - up to 10%. The volume of distribution is 0.57-0.76 l / kg. Well distributed throughout the body, penetrating all tissues and fluids, including cerebrospinal, pleural, ascites; high concentrations are created in the lung tissue, kidneys, liver, muscles, saliva and sputum. Penetrates through the placental barrier and into breast milk. It is metabolized in the liver by acetylation with the formation of inactive products. The liver is acetylated with N-acetyltransferase to form N-acetyl-isoniazid, which is then converted to isonicotinic acid and monoacetylhydrazine,which has a hepatotoxic effect by forming a mixed oxidase system of cytochrome P450 upon N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with "slow" acetylation, there is little N-acetyltransfusion. It is an inhibitor of the isoenzymes CYP2C9 and CYP3A2E1. Is the inducer of the isoenzyme CYP2E1. Half-life (T1/2) for: "fast" acetylators - 0.5-1.6 hours; for "slow" - 2-5 hours With renal failure T1/2 can increase to 6.7 hours. Despite the fact that the indicator T1/2 varies considerably depending on the individual intensity of the acetylation processes, the average value T1/2 is 3 hours (intake of 600 mg) and 5.1 hours (900 mg). With repeated appointments, it is shortened to 2-3 hours. It is excreted mainly by the kidneys: 75 to 95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites - N-acetyl-isoniazid and isonicotinic acid. In this case, the "fast" acetylation content of N-acetylisiniazide is 93%, and in "slow" acetylsinides it is not more than 63%. Small amounts are excreted by the intestine. The drug is removed from the blood during hemodialysis; 5 h hemodialysis allows you to remove from the blood to 73% of the drug.

    Indications:Tuberculosis of any localization, in adults and children, treatment and prevention, including in combination therapy.
    Contraindications:

    - Hypersensitivity to the components of the drug;

    - epilepsy, epileptic syndrome, propensity to convulsive conditions, neuritis (polyneuritis), psychosis;

    - poliomyelitis (including in the anamnesis);

    - severe hepatic insufficiency (hepatitis, obstructive jaundice, cirrhosis), drug-induced hepatitis and liver failure (in the background of the previous treatment with isoniazid), liver disease in the acute stage;

    - violation of blood clotting and hemopoiesis (hematopoiesis);

    - Children under 3 years old.

    Carefully:In patients with severe heart failure, hypertension, ischemic heart disease, widespread atherosclerosis, nervous system disease, hypothyroidism.
    Pregnancy and lactation:In pregnancy and during lactation apply only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.
    Dosing and Administration:

    Inside. Isozid Comp. should be taken on an empty stomach, without chewing and washing down with a sufficient amount of water.

    Dosage regimen, duration of application is determined by the physician individually depending on the age and body weight of the patient, as well as the prescribed integrated regimen and recovery process.

    Adults: the daily dose is 5 mg (3-8 mg) of isoniazid per kilogram of body weight of the patient. The maximum daily dose of 300 mg (1 tablet).

    With intermittent therapy (2-3 times, per week): the dose is 15 mg / kg, with a maximum daily dose of 900 mg (3 tablets). Children and teenagers under 18: 5-10 mg / kg body weight, the maximum daily dose of 300 mg: children from 3 years: 8-10 mg / kg body weight (1/2 tablet); children 6-9years: 7-8 mg / kg body weight (1/2 tablet); children 10-14 years: 6-7 mg / kg body weight (1 tablet); adolescents 15 g 18 years: 5-6 mg / kg body weight (1 tablet);

    For the purpose of prevention: 5-10 mg / kg / day in 2 divided doses for 2 months. Dosing in case of impaired renal function: there is no need, dose reduction, a daily dose of 300 mg.

    Dose reduction recommended before 100-200 mg at- day for "slow acetylators".

    Dialysis patients may reduce the dose to 200 mg (the minimum level of serum levels should be below 1 mg / L, the determination of the level should be made 24 hours after application).

    Dosage if liver function is impaired: it is recommended to reduce the dose to 100-200 mg / day.

    Duration of treatment: prevention of tuberculosis infection of uninfected patients with negative tuberculin tests (chemoprophylaxis) - up to 6 months.

    Prophylaxis in patients with diagnosed tuberculin conversion or tuberculin-positive patients without clinical or other signs characteristic of tuberculosis (chemoprophylaxis) - within 6 months.

    Treatment of tuberculosis (chemotherapy) - from 6 to 12 months.

    Side effects:

    Side effects are listed below in descending frequency: very often (more than 10%), often (1-10,% of patients), infrequently (0.1-1% of patients), rarely (0.01-0.1% of patients) , very rarely (less than 0.01% of patients, including individual reports).

    Isoniazid-related

    From the nervous system: often: dizziness, headache - pain, mental changes (impairment of mental abilities and ability to respond, increased irritability, loss of self-control, etc.), peripheral neuropathy manifested by paresthesia of the skin of hands and feet, polyneuropathy, seizures (epileptiform seizures), toxic, encephalopathy, psychosis , insomnia; rarely: neuritis and atrophy of the optic nerve.

    From the digestive system: often: ongoing increase in the activity of "hepatic" transaminases in the blood plasma during the first month of treatment; rarely - nausea, vomiting, diarrhea or constipation, epigastric pain, toxic hepatitis, persistent increase in enzyme activity.

    From the urinary system: rarely: the appearance of blood (microhematuria) and protein in the urine.

    Allergic reactions: rarely: hypersensitivity reactions of various degrees, with such symptoms as fever, rash (skin rashes, exanthema), swollen lymph nodes, vasculitis, itching, arthralgia, "lupus-like" syndrome.

    From the cardiovascular system: infrequently: heart palpitations, angina, increased blood pressure.

    From the side of blood and the system of homeostasis: infrequently: thrombocytopenia, platelet change the functional properties expressed by the reduction or absence of granulocytes (agranulocytosis), disorders of blood (haemolytic, sideroblastic and aplastic anemia), increase of eosinophils (eosinophilia), acidosis.

    Allergic reactions: rarely: with irregular admission or with the resumption of treatment after a break flu-like syndrome (fever, chills,headache, - dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure ..

    Countermeasures

    In cases of peripheral neuritis, additionally take high doses of vitamin B6.

    Acute hypersensitivity reactions require immediate discontinuation of the drug and at the necessity of taking antihistamines of glucocorticosteroids, symptomatic agents, if necessary, artificial respiration.

    If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects not listed in the instructions, inform the doctor about it.

    Overdose:

    Symptoms: convulsions, headache, nausea, anxiety, weakness, vomiting, hallucinations, hyperreflexia, collapse, hypothermia, respiratory depression, cyanosis, coma.

    In case of an overdose, consult a doctor immediately.

    Treatment: the introduction of vitamin B6, sodium bicarbonate (with the development of metabolic acidosis), the use of anticonvulsant, sedatives, if necessary artificial respiration.

    Interaction:

    Isoniazid

    When combining isoniazid with paracetamol, hepato- and nephrotoxicity increases, because isoniazid induces the system, cytochrome P450, resulting in increased metabolism of paracetamol to toxic products.

    Ethanol increases the hepatotoxicity of isoniazid and speeds up its metabolism. Isoniazid reduces the metabolism of theophylline, alfentanil, which leads to an increase in their concentration in the blood.

    Cycloserine and disulfiram strengthens the adverse central effects of isoniazid.

    Isoniazid increases the hepatotoxicity of rifampicin.

    Combination with pyridoxine reduces the risk of peripheral neuritis.

    Caution should be combined with potentially neuro-, hepato- and nephrotoxic drugs, because of the risk of side effects.

    Enhances the effect of derivatives of coumarin and indandione, benzodiazepines, carbamazepine, theophylline, as it reduces their metabolism due to the activation of the cytochrome P450 system.

    It suppresses the metabolism of phenytoin, which leads to an increase in its concentration and an increase in the toxic effect (correction of the dosing regimen of phenytoin may be necessary, especially in patients with slow acetylation of isoniazid).

    Glucocorticosteroids accelerate the metabolism of isoniazid in the liver and reduce its active concentrations in the blood.

    Pyridoxine

    Strengthens the action of diuretics, weakens the activity of levodopa. Isoniazid, penicillamine, cycloserine and estrogen-containing oral contraceptives weaken the effect of pyridoxine.

    Special instructions:

    To slow the development of microbial resistance is prescribed together with other antituberculous drugs.

    In connection with the different metabolic rate before the use of isoniazid, it is expedient to determine the rate of its inactivation by the content of the active substance in the blood and urine. With rapid inactivation isoniazid used in higher doses.

    During the treatment, cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack) should be avoided, since with the simultaneous use of them with isoniazid, reactions (skin flushing, itching, heat or cold sensation, palpitation, increased sweating, chills, headache, dizziness) associated with the suppression of monoamine oxidase and diaminoxidase activity and leading to a disruption of the metabolism of tyramine and histamine contained in fish and cheese.

    It should be borne in mind that isoniazid can cause hyperglycemia with secondary glucosuria; tests with the restoration of Cu2 + can be false positive, and the enzyme tests for glucose drug does not affect.

    Laboratory indicators - alanine aminotransferase (ALT), aspartate aminotransferase (ACT), serum bilirubin concentration can transiently increase without clinical manifestations. When there are signs of toxic hepatitis the drug is canceled.

    Effect on the ability to drive transp. cf. and fur:Because of the possibility to influence the patient's reactions during the treatment process, care should be taken when driving vehicles and engaging in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions. The effect is enhanced by the simultaneous intake of alcohol.
    Form release / dosage:
    Coated tablets containing 300 mg of isoniazid and 60 mg of pyridoxine hydrochloride.
    Packaging:

    For 100 tablets in a white container made of polypropylene with a white lid of low density polyethylene with a ring of the first opening, the empty space is filled with foam rubber sealant.A container of 100 tablets together with the instruction for use is placed in a cardboard box.

    For 1000 tablets in a brown PVC container with a protective membrane of low-density polyethylene and a black screw cap made of bakelite with a PVC liner, the empty space is filled with foam rubber sealant, on top of which is placed the instruction for use.

    For 10, 20, 30, 40 containers of 1000 tablets are placed in a group package - a cardboard box (for hospitals).

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    The drug should not be used after the expiry date indicated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N009789
    Date of registration:23.09.2011
    Expiration Date:Unlimited
    The owner of the registration certificate:Fatol Artsynmittel GmbHFatol Artsynmittel GmbH Germany
    Manufacturer: & nbsp
    Representation: & nbspSVYCH LLC SVYCH LLC Russia
    Information update date: & nbsp23.10.2017
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