Isoniazid tablets - instructions for use, dose, side effects, contraindications

Active substanceIsoniazidIsoniazid

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Isoniazid

pills inwards

TATHIMFARMPREPARATY, JSC Russia

Isoniazid

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FARMASINTEZ, JSC (Irkutsk) Russia

Isoniazid-Darnitsa

solution d / inhal. w / m in / in e / tracheal.

DARNITSA PHARMACEUTICAL FIRM, CJSC Ukraine

Isoniazid-Ferein

solution for injections

BRYNTSALOV-A, CJSC Russia

Isoniazid Tablets

pills inwards

BIOSINTEZ, PAO Russia

Dosage form: & nbsppills

Composition:

Active substance:

Isoniazid -100 mg -200 mg, -300 mg.

Excipients:

calcium stearate monohydrate -1,1 mg -2.2 mg -3,3 mg

polysorbate-80 (twin 80) -0.15 mg -0.3 mg -0.5mg

crospovidone (clolidon CL-M) -1,1 mg - 2.2 mg - 3.3 mg

potato starch - a sufficient amount until

tablet weight

-110 mg -220 mg -330 mg.

Description:Tablets are white or white with a creamy shade of color, a flat-cylindrical shape with a bevel. Tablets with a dosage of 200 mg and 300 mg with a risk.

Pharmacotherapeutic group:Anti-tuberculosis drug

ATX: & nbsp

J.04.A.C.01 Isoniazid

Pharmacodynamics:Anti-tuberculosis drug; 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 delta 2-unsaturated fatty acids into mikelic 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 in the ratio of 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 period of maximum concentration is 1-2 hours, the maximum concentration after taking 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. In the liver acetylated N-acetyltransferase with formation of N-acetylisoiniazide, which is then converted to isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by forming a cytochrome P450 system at Nhydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with "slow" acetylation, little N-acetyltransferase. Is isoenzyme inducer CYP2E1. the half-life for "fast acetylators" is 0.5-1.6 hours; for "slow" - 2-5 hours. With renal failure, the elimination half-life can increase to 6.7 hours. Half-life for children aged 1.5 to 15 years is 2.3-4.9 hours, and in newborns - 7.8-19.8 hours (which is due to the imperfection of acetylation processes 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 (ingestion 600 mg) and 5.1 hours (900 mg). At repeated appointments the half-life period is shortened to 2-3 hours.

Excreted mainly by the kidneys: within 24 hours 75-95% of the drug is excreted, mainly in the form of inactive metabolites - N-acetylisoiniazide and isonicotinic acid. At the same time, "fast acetylators" contain N-acetyl isosine is up to 93%, while in "slow" - not more than 63%. Small amounts are excreted with feces. The drug is removed from the blood during hemodialysis; 5 hour 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, hepatic insufficiency, 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, arterial hypertension ), hypothyroidism, pregnancy (not prescribed in a dose above 10 mg / kg)

Dosing and Administration:

Inside, after meals, 600-900 mg / day in 1-3 divided doses, the maximum single dose is 600 mg, daily - 900 mg.

Children - 5-15 mg / kg / day, the frequency of reception - 1-2 times a day, the maximum dose - 500 mg / day. For the prevention of 5-10 mg / kg / day in 2 divided doses for 2 months.

During pregnancy and with severe form of pulmonary heart failure, severe atherosclerosis, ischemic 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; rare - excessive fatigue or weakness, irritability, euphoria, insomnia, optic neuritis, polyneuritis, toxic psychosis, emotional lability, depression, convulsions, toxic neuropathy, memory impairment.

From the cardiovascular system: palpitation, angina, increased blood pressure.

From the digestive system: nausea, vomiting, gastralgia; an increase in the activity of alanine amineslansferase, 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, arthrapia, lymphadenopathy, vasculitis.

From the side of metabolism: hypovitaminosis B₆, 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 admission: nausea, vomiting; dizziness, blurred speech, visual impairment, visual hallucinations. With severe overdose: 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 taken 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 for 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 for 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 case of an overdose with isoniazid 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 sodium hydrogen carbonate 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, hepatotoxicity and nephrotoxicity increase; 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 indandione, benzodiazepines, carbamazepine, theophylline,because it reduces their metabolism due to the activation of cytochrome P450 isoenzymes.

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 dosing 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 medicines (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).

When used simultaneously with enflurane isoniazid can increase the formation of inorganic fluoride metabolite, which has a nephrotoxic effect. When taken together with rifampicin reduces the concentration of ketoconazole in the blood. Increases the concentration of valproic acid in the blood (monitoring of valproic acid concentration is required, correction of the dosing regimen may be required).

Special instructions:

In some cases, fatal drug hepatitis develops during treatment, which may occur even after several months of use. The risk rises with age (the highest frequency in the age group is 35-64 years), especially with daily consumption of ethanol. Therefore, every month it is necessary to monitor the function of the liver, people over 35 years of age, the function of the liver is further examined before treatment. In addition to ethanol use, additional risk factors are chronic liver disease, parenteral drug use and the postpartum period; under these circumstances, monitoring of liver function (laboratory and clinical) should be conducted more often. Patients should be informed of the need to report any manifestations of liver damage (unexplained anorexia, nausea, vomiting, darkening of the urine, jaundice, rash, paresthesia of the hands and feet, weakness, fatigue or fever lasting more than 3 days, abdominal pain, especially in the right upper quadrant ). In these cases isoniazid immediately cancel. Patients who have previously undergone isoniazid hepatitis are prescribed alternative antituberculous drugs.If it is necessary to resume therapy, it begins after a complete resolution of clinical and laboratory signs of hepatitis with subsequent monitoring of liver function. With any signs of relapse isoniazid immediately cancel. In patients with acute liver disease, preventive isoniazid should be postponed.

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 dynamics of the content in the blood and urine). In fast acetylators isoniazid used in higher doses.

At the risk of peripheral neuritis (patients older than 65 years old, concomitant diabetes mellitus, pregnancy, chronic renal failure, alcoholism, vitamin B deficiency due to malnutrition, concomitant anticonvulsant therapy), the appointment of 10-25 mg / day of pyridoxine is recommended.

During treatment, avoid eating cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack),since the simultaneous use of them with isoniazid may cause reactions (skin hyperemia, itching, sensation of heat or cold, 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 copper reduction can be false positive; the drug does not affect the enzymatic glucose tests.

Effect on the ability to drive transp. cf. and fur:Taking into account possible side effects, during the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 100 mg, 200 mg, 300 mg.

Packaging:

For 50 or 100 tablets in cans of orange glass or in polymer cans. For 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered or in contour non-cellular package made of paper with polyethylene coating.

Each jar, 2, 5 or 10 contour mesh or contour non-jawed packages together with the instruction for use is placed in a pack of cardboard.

100 contour mesh or contour non-jawed packages with an equal number of instructions for use are placed in cardboard boxes (for hospitals).

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:5 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001918

Date of registration:30.09.2011

Expiration Date:Unlimited

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp23.10.2017

Illustrated instructions

Instructions

Isoniazid Tablets (Isoniazid tablets)