Isoniazid (Isoniazid)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceIsoniazidIsoniazid
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  • Isoniazid
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    TATHIMFARMPREPARATY, JSC     Russia
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    FARMASINTEZ, JSC (Irkutsk)     Russia
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    solution d / inhal. w / m in / in e / tracheal. 
    DARNITSA PHARMACEUTICAL FIRM, CJSC     Ukraine
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    BRYNTSALOV-A, CJSC     Russia
  • Isoniazid Tablets
    pills inwards 
    BIOSINTEZ, PAO     Russia
    • Dosage form: & nbsppills
    Composition:

    Composition for the dosage of 100 mg

    1 tablet contains:

    Active substance: Isoniazid 0.1 g.

    Excipients: potato starch - 0.00340 g, magnesium stearate - 0.00055 g, stearic acid - 0.00055 g, silicon dioxide colloid (aerosil) - 0.00550 g.

    Composition for a dosage of 300 mg

    1 tablet contains:

    Active substance: Isoniazid - 0.3 g.

    Excipients: potato starch - 0.01020 g, magnesium stearate 0.00165 g, stearic acid 0.00165 mg, silicon dioxide colloid (aerosil) 0.01650 g.

    Description:Tablets are round planar cylindrical with a facet and a white or white color with a creamy shade of color, marble is allowed.
    Pharmacotherapeutic group:Anti-tuberculosis drug
    ATX: & nbsp

    J.04.A.C.01   Isoniazid

    Pharmacodynamics:

    Antituberculous; acts bacteriostatically. Is a prodrug - mycobacterial catalase peroxidase metabolizes isoniazid to the active metabolite, which, when bound to the enoyl (acyl-transfer protein) reductase of fatty acid synthase II, disrupts the conversion of delta2-unsaturated fatty acids into mycolic acid. The latter is a branched chain fatty acid that, when combined with arabinogalactan (polysaccharide), participates in the formation of the components of the cell wall of Mycobacterium tuberculosis. Isoniazid is also an inhibitor of mycobacterial catalase peroxidase, which reduces the protection of the microorganism against reactive oxygen species and hydrogen peroxide.

    Isoniazid is also active against a small number of strains of Mycobacterium kansasii (for infections caused by this pathogen, it is necessary to determine the sensitivity to isoniazid before starting treatment).

    Pharmacokinetics:

    Isoniazid quickly and completely absorbed when ingested, food reduces absorption and bioavailability. The effect of "first passage" through the liver has a great influence on the bioavailability index. The time required to reach the maximum concentration is 1-2 hours, the maximum concentration 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-acetylisoiniazide, which is then converted to isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by forming a cytochrome system R450 with N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with "slow" acetylation, there is little N-acetyltransferase. Is the inducer of the isoenzyme CYP2E1. The half-life for "fast acetylators" is 0.5-1.6 hours; for "slow" - 2-5 hours. In case of renal insufficiency, the half-life may increase to 6.7 hours. The half-life period for children aged 1.5 to 15 years is 2.3-4.9 hours, and in newborns - 7,8-19,8 h (which is explained by the imperfection of the processes of acetylation in newborns).Despite the fact that the half-life index varies significantly depending on the individual intensity of the acetylation processes, the average value of the half-life is 3 hours (intake 600 mg) and 5.1 hours (900 mg). At repeated appointments the half-life period is shortened to 2-3 hours.

    It is excreted mainly by the kidneys: 75-95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites - N-acetylisonic acid and isonicotinic acid. At the same time, "fast acetylators" contain N-acetylisiniazide content of 93%, while "slow" - 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 (any localization, in adults and children, treatment and prevention, as part of combination therapy).

    Contraindications:Hypersensitivity, drug hepatitis and liver failure (against the background of the previous treatment of isoniazid), liver disease in the acute stage, children under 3 years (for this dosage form).
    Carefully:

    Alcoholism, liver failure,renal failure, seizures, age over 35, long-term use of other drugs, cancellation of isoniazid therapy in history, peripheral neuropathy, HIV infection, decompensated diseases of the cardiovascular system (chronic heart failure, angina pectoris, hypertension), hypothyroidism.

    Pregnancy and lactation:

    In pregnancy, do not prescribe the drug at a dose above 10 mg / kg. It is recommended to stop breastfeeding for the duration of treatment.

    Dosing and Administration:

    Inside, after eating adults 600-900 mg / day in 1-3 doses, the maximum single dose - 600 mg, daily - 900 mg; children older than 3 years - 5-15 mg / kg / day, the frequency of admission -1-2 times a day, the maximum dose - 500 mg / day.

    For prophylaxis - inside, at 5-10 mg / kg / day in 2 doses for 2 months.

    During pregnancy and with a severe form of pulmonary heart failure, severe atherosclerosis, coronary heart disease and hypertension should not be prescribed in doses greater than 10 mg / kg.
    Side effects:

    From the nervous system: headache, dizziness, paresthesia, numbness of the extremities,peripheral neuropathy; rarely excessive fatigue or weakness, irritability, euphoria, insomnia, optic neuritis, polyneuritis, toxic psychosis, emotional lability, depression, convulsions, toxic neuropathy, memory impairment.

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

    From the digestive system: nausea, vomiting, gastralgia; increased activity of alanine aminotransferase, asparagine aminotransferase, hyperbilirubinemia, bilirubinuria, jaundice; rarely - toxic hepatitis, including fatal.

    From the hematopoiesis: agranulocytosis, hemolytic, sideroblastic or aplastic anemia, thrombocytopenia, eosinophilia.

    Allergic reactions: skin rash (cortex, maculopapular, exfoliative, purpura), itching, fever, arthralgia, lymphadenopathy, vasculitis.

    From the side of metabolism: hypovitaminosis Vb, pellagra, hyperglycemia, metabolic acidosis, gynecomastia.

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

    If any of the side effects indicated in the manual are aggravated, or any other side effects not indicated in the instructions are noted, you should inform the doctor immediately.

    Overdose:

    Symptoms occur within 0.5-3 hours after application: nausea, vomiting, dizziness, blurred speech, visual impairment, visual hallucinations. With the expressionoverdose: respiratory distress syndrome, central nervous system depression rapidly shifting from stupor to coma, severe non-curable convulsions, severe metabolic acidosis, acetonuria, hyperglycemia.

    Treatment: in severe overdose (80-150 mg / kg), insufficient therapy leads to neurotoxicity with a fatal outcome. With adequate therapy, the prognosis is favorable.

    With asymptomatic overdose: Activated carbon, gastric lavage. When taking in a dose of more than 80 mg / kg in the same dose intravenously administered pyridoxine, if the dose of isoniazid is unknown, then 5 g of pyridoxine are administered intravenously to adults, 80 mg / kg for children within 30-60 minutes.

    At clinical displays: adequate ventilation, maintenance of activity of cardiovascular system, prevention of aspiration of gastric contents.If the dose of isoniazid is known, the same amount of pyridoxine is administered intravenously bolus within 3-5 minutes. If the dose of isoniazid is unknown, then 5 g of pyridoxine are injected intravenously, 80 mg / kg for children. If the convulsions do not stop, the dose can be repeated. It is rare to prescribe a dose of more than 10 g. The maximum safe dose of pyridoxine in an isoniazid overdose is unknown. If pyridoxine is ineffective, diazepam.

    It is necessary to control the content of electrolytes, urea, glucose and partial pressure of gases in the blood. With the development of metabolic acidosis of sodium, bicarbonate can enhance hypercapnia (continuous monitoring is necessary).

    Dialysis is prescribed if seizures and acidosis are not stopped by pyridoxine, diazepam and sodium bicarbonate.
    Interaction:

    When combined with paracetamol, hepato- and nephrotoxicity increases; isoniazid induces a system of cytochrome P450, which increases the metabolism of paracetamol to toxic products.

    Ethanol increases the hepatotoxicity of isoniazid and speeds up its metabolism.

    Reduces the metabolism of theophylline, which can lead to an increase in its concentration in the blood.

    Reduces metabolic transformations and increases the concentration in the blood of alfentanil.

    Cycloserine and disulfiram enhance the adverse central effects of isoniazid.

    Increases 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 indanedione, benzodiazepines, carbamazepine, theophylline, since it reduces their metabolism due to the activation of cytochrome isoenzymes R450.

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

    Suppresses the metabolism of phenytoin, which leads to an increase in its concentration in the blood and increased toxic effect (correction of the dosage regimen of phenytoin may be necessary, especially in patients with slow acetylation of isoniazid); should be considered when administered as an anticonvulsant with an overdose of isoniazid.

    Antacid drugs (especially aluminum-containing drugs) slow down absorption and reduce the concentration of isoniazid in the blood (antacids should be taken no earlier than 1 hour after taking isoniazid).

    Form release / dosage:Tablets 100 mg, 300 mg.
    Packaging:

    10, 20 or 25 pieces in a planar cell package.

    By 2, 4, 5 or 10 contour mesh packages together with instructions for use in a cardboard package.

    100 pieces in an orange glass bank along with instructions for use in a pack of cardboard.

    Storage conditions:In dry, dark place at a temperature of no higher than 25 ° C.
    Shelf life:5 years.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-001157
    Date of registration:11.11.2011 / 27.02.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:TATHIMFARMPREPARATY, JSC TATHIMFARMPREPARATY, JSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp23.10.2017
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