Isoniazid - instructions for use, doses, side effects, contraindications

Excipients: potato starch - 20,10 mg; silicon dioxide colloidal - 2.40 mg; povidone (medium molecular weight polyvinylpyrrolidone, kollidon 25) - 6.00 mg; magnesium stearate - 1.50 mg.

Description:Tablets are white or white with a creamy shade of color, flat-cylindrical, with a risk and a facet.

Pharmacotherapeutic group:Anti-tuberculosis drug

ATX: & nbsp

J.04.A.C.01 Isoniazid

Pharmacodynamics:Anti-tuberculosis drug; 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).

Pharmacokinetics:Absorption - high (intake during eating reduces absorption). Time to reach a maximum concentration of 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%. 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. The half-life is 3 hours (inside 600 mg) and 5.1 h (900 mg). With repeated appointments, the elimination half-life is shortened to 2-3 hours. It is metabolized in the liver by acetylation to inactive products. It is excreted mainly by the kidneys: 75-95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites. Small amounts are output through 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 older than 3 years, treatment and prevention, including as part of combination therapy).

Contraindications:

Hypersensitivity, epilepsy, epileptic syndrome, poliomyelitis (including in the anamnesis), chronic renal failure,cirrhosis of the liver, 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:Chronic heart failure, arterial hypertension, ischemic heart disease, widespread atherosclerosis, nervous system disease, hypothyroidism, pregnancy (not prescribed in a dose above 10 mg / kg), alcoholism.

Pregnancy and lactation:During pregnancy should not be prescribed in doses greater than 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 (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 the purpose of prophylaxis - inside, at 5-10 mg / kg / day in two divided doses per day, for 2 months.

During pregnancy and with 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,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 gastrointestinal tract: nausea, vomiting, toxic hepatitis.

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

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

Overdose:

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

Treatment: peripheral polyneuropathy (vitamins B6, B1, B12, ATP, glutamic acid, nicotinamide, massage, physiotherapy procedures); convulsions (in / m vitamin B6 - 200-250 mg, iv 40% dextrose solution - 20 ml, in / m 25% solution of magnesium sulfate - 10 ml, diazepam); abnormal liver function (methionine, lipid, ATP, vitamin B12).

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 rifampin.

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 reduces their metabolism by activating the cytochrome P450 system.

Glucocorticosteroid hormones accelerate metabolism in the liver and reduce active concentrations in the blood.

It suppresses the metabolism of phenytoin, which leads to an increase in its concentration in the blood 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).

Antacid medicines (especially aluminum-containing drugs) slow down absorption and reduce the concentration of erniazid 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. Reduces the concentration of ketoconazole in the blood.

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 dynamics of the content in the blood and urine). With rapid inactivation isoniazid used in higher doses.

At a risk of peripheral neuritis (patients over 65 years of age, patients with diabetes, pregnant women,patients with chronic renal failure, alcoholism patients, with eating disorders, concomitant anticonvulsant therapy), the appointment of 10-25 mg / day pyridoxine is recommended.

During the treatment, cheese and fish should be avoided, 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 MAO activity suppression and diaminoksidazy 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, and the enzyme tests for glucose drug does not affect. Laboratory indicators - "liver" enzymes, the concentration of bilirubin in the blood serum can transiently increase without clinical manifestations.

When there are signs of toxic hepatitis the drug is canceled.

Form release / dosage:

Tablets 300 mg.

Packaging:

10 tablets per contour cell pack.For 10 contour packs with instructions for use in a pack of cardboard.

On 100, 500 and 1000 tablets in a package polyethylene. A polyethylene bag together with instructions for use in a plastic jar (for hospitals).

Storage conditions:

In a dry, protected from light 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 expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N000519 / 01

Date of registration:01.07.2008 / 03.07.2017

Expiration Date:Unlimited

The owner of the registration certificate:FARMASINTEZ, JSC (Irkutsk) FARMASINTEZ, JSC (Irkutsk) Russia

Manufacturer: & nbsp

FARMASINTEZ, JSC (Irkutsk) Russia

Information update date: & nbsp23.10.2017

Illustrated instructions

Instructions

Isoniazid (Isoniazid)