Isozid 200 (Tablets) Instructions for Use

Marketing Authorization Holder

Fatol Arzneimittel, GmbH (Germany)

ATC Code

J04AC01 (Isoniazid)

Active Substance

Isoniazid (Rec.INN registered by WHO)

Dosage Form

Isozid 200

Tablets 200 mg: 100 pcs.

Dosage Form, Packaging, and Composition

100 pcs. – PVC containers.

Clinical-Pharmacological Group

Antituberculosis drug

Pharmacotherapeutic Group

Antitubercular agent

Pharmacological Action

Antituberculosis agent. It has a bactericidal effect. Isoniazid is active against extracellular and intracellular Mycobacterium tuberculosis, primarily against actively dividing ones. Its exact mechanism of action is unknown. It is assumed to be associated with the suppression of the synthesis of mycolic acids, which are part of the mycobacterial cell wall.

Pharmacokinetics

After oral administration, it is rapidly absorbed from the gastrointestinal tract. When taken with food, absorption and bioavailability are reduced. It is widely distributed in all body tissues and fluids, including cerebrospinal, pleural, and ascitic fluids; high concentrations are achieved in lung tissue, kidneys, liver, muscles, saliva, and sputum. Plasma protein binding is very low (0-10%). V_d – 0.57-0.76 L/kg. It is metabolized in the liver. Excreted in the urine, a small amount – in the feces.

It crosses the placental barrier and is excreted in breast milk.

Indications

Treatment and prevention of all forms of tuberculosis caused by M. tuberculosis sensitive to isoniazid, as part of combination therapy.

ICD codes

Dosage Regimen

Administer Isozid 200 orally, intramuscularly, intravenously, or by intracavitary instillation.

Establish the dose, route, and duration of therapy individually based on disease form and severity, acetylation status, and patient tolerance.

For adults, the typical oral dosage is 5 mg/kg once daily, up to a maximum of 300 mg per day. Alternatively, administer 15 mg/kg (up to 900 mg) two or three times per week under direct observation.

For children, calculate the dose based on body weight: 10-15 mg/kg once daily, up to a maximum of 300 mg per day. For intermittent therapy, use 20-40 mg/kg (up to 900 mg) two or three times per week.

For preventive therapy, the standard adult dose is 300 mg once daily. The pediatric prophylactic dose is 10 mg/kg once daily, up to 300 mg.

Take tablets on an empty stomach, at least one hour before or two hours after meals, to ensure optimal absorption.

Concurrently administer pyridoxine (Vitamin B6) to prevent and treat peripheral neuropathy, especially in malnourished patients or those at high risk.

Adjust dosage in patients with severe renal impairment and monitor hepatic function closely in all patients, particularly those with pre-existing liver conditions.

Always use isoniazid in combination with other antituberculosis drugs to prevent the development of resistant mycobacterial strains.

Adverse Reactions

From the hematopoietic system: frequency unknown – eosinophilia, bone marrow suppression, granulocytopenia, thrombocytopenia, agranulocytosis, sideroblastic anemia, hemolytic or megaloblastic anemia, pyridoxine-deficiency anemia, coagulopathy, aplastic anemia.

From the immune system: frequency unknown – exanthema (including acneiform, especially in young patients), exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity, fever, asthma, myalgia and arthralgia, anaphylactic reactions, anaphylactic shock, systemic lupus erythematosus, lupus-like syndrome, lymphadenopathy.

From the endocrine system: frequency unknown – hyperfunction of the adrenal cortex (Cushing’s syndrome) and the anterior pituitary lobe (with menstrual cycle disorders in women or gonadotropic disorders/gynecomastia in men) – these phenomena are predominantly reversible.

From metabolism: very rare – hypoglycemia; frequency unknown – hyperglycemia, metabolic acidosis, pellagra (nicotinic acid deficiency).

From the psyche: frequency unknown – mental disorders (irritability, anxiety), decreased concentration, depression, psychoses (manifest, catatonic, or paranoid), euphoria.

From the nervous system: frequent – peripheral polyneuropathy with paresthesia, sensory disturbances, headache, dizziness; frequency unknown – seizures, drowsiness, lethargy, hyperreflexia.

From the organ of vision: rare – optic nerve atrophy; frequency unknown – optic neuritis, diplopia, strabismus.

From the hearing organ and labyrinthine disorders: frequency unknown – deafness, tinnitus, vertigo (in patients with end-stage renal failure).

From the cardiovascular system: frequency unknown – arrhythmia, vasculitis, increase or decrease in blood pressure.

From the respiratory system: frequency unknown – acute respiratory distress syndrome, interstitial lung disease.

From the digestive system: frequent – diarrhea, constipation, regurgitation, abdominal bloating, vomiting; frequency unknown – pancreatitis, dry mouth.

From the liver and biliary tract: very common – increased activity of liver transaminases; uncommon – hepatitis; frequency unknown – acute liver failure, liver damage, jaundice, acute hepatitis (including fatal).

From the musculoskeletal system: frequent – muscle tremor; frequency unknown – rheumatic syndrome, rhabdomyolysis.

From the urinary system: frequency unknown – glomerulonephritis (mainly reversible), dysuria.

From the skin and subcutaneous tissues: rare – toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

Contraindications

Hypersensitivity to isoniazid; drug-induced hepatitis and/or other severe adverse reactions that developed during previous treatment with isoniazid; liver diseases in the acute stage; severe hepatic insufficiency; children under 3 years of age (for oral administration).

With caution: alcoholism, mild and moderate hepatic insufficiency, history of liver dysfunction or chronic liver dysfunction, renal failure, convulsive seizures, age over 35 years, long-term use of other potentially hepatotoxic drugs, history of isoniazid therapy discontinuation, peripheral neuropathy, HIV infection, decompensated cardiovascular diseases (chronic heart failure, angina pectoris, arterial hypertension), hypothyroidism, diabetes mellitus, exhaustion, history of mental illness, “slow acetylators”, female sex, pregnancy (for parenteral administration).

Use in Pregnancy and Lactation

Isoniazid crosses the placenta. During pregnancy, it should be used only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

Isoniazid crosses the placental barrier and is excreted in breast milk. If use during lactation is necessary, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

The use of isoniazid is contraindicated in patients with severe hepatic insufficiency, with liver diseases in the acute stage.

It should be prescribed with caution to patients with mild and moderate hepatic impairment; strict monitoring of liver enzymes is necessary.

Use in Renal Impairment

Use with caution in patients with renal failure.

Pediatric Use

Isoniazid is contraindicated for oral administration in children under 3 years of age.

Geriatric Use

Should be used with caution in elderly patients.

Special Precautions

To avoid the rapid development of resistance of Mycobacterium tuberculosis, Isoniazid is used in combination with other antituberculosis drugs.

In some cases, fatal drug-induced hepatitis develops during treatment with isoniazid, which can occur even several months after the end of use. The risk increases with age (highest frequency in the age group 35-64 years), especially with daily ethanol consumption. Therefore, liver function should be monitored monthly in all patients; in persons over 35 years of age, liver function is additionally examined before starting treatment. If ALT and AST activity increases by 4 times or more, or the concentration of bilirubin in the blood increases, isoniazid treatment should be discontinued.

To reduce side effects, pyridoxine (orally or intramuscularly), or glutamic acid (orally), or thiamine (intramuscularly) is prescribed simultaneously with isoniazid.

It should be taken into account that Isoniazid is metabolized in the liver by acetylation to inactive metabolites. The degree of acetylation is determined by genetic factors. Due to the unequal degree of metabolism, it is advisable to determine the rate of its inactivation by the content of the active substance in the blood and urine before using isoniazid. In patients who have rapid inactivation, Isoniazid is used in higher doses.

During treatment with isoniazid, consumption of cheese (especially Swiss or Cheshire) and fish (especially tuna, sardinella) should be avoided, since when taken simultaneously with isoniazid, reactions may occur (skin hyperemia, itching, sensation of heat or cold, palpitations, increased sweating, chills, headache, dizziness) associated with the suppression of MAO and DAO activity and leading to impaired 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 ion reduction may be false-positive; it does not affect enzymatic glucose tests. Simultaneous consumption of alcohol contributes to increased hepatotoxic reactions.

Patients with intolerance to ethionamide, pyrazinamide, nicotinic acid, or other chemically similar substances may have intolerance to isoniazid. Laboratory parameters of ALT and AST, serum bilirubin concentration may transiently increase without clinical manifestations.

After the injection, the patient must observe bed rest for 1-1.5 hours.

Effect on the ability to drive vehicles and mechanisms

During the treatment period, patients should avoid driving vehicles and other activities requiring high concentration and speed of psychomotor reactions, due to the possibility of developing adverse reactions from the nervous system.

Drug Interactions

Isoniazid inhibits the CYP2C19, CYP1A2, CYP2A6, CYP2E1, and CYP3A isoenzymes of the hepatic cytochrome P450 system, which can lead to a slowdown in the elimination of drugs metabolized by these enzymes.

In “slow acetylators” and in patients simultaneously receiving aminosalicylic acid, tissue concentrations of isoniazid may be increased and the frequency of side effects may be increased.

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

Isoniazid increases the frequency and severity of liver function disorders in combination with rifampicin in patients with pre-existing liver diseases.

Isoniazid increases the blood concentration of phenytoin, enhancing its side effects such as drowsiness and ataxia, reduces the effectiveness of oral combined contraceptive drugs, glipizide, tolbutamide, tolazamide, thiamine; suppresses the elimination of triazolam; reduces the content of zinc ions in the blood. Isoniazid enhances the effect of coumarin derivatives, indandione, benzodiazepines, carbamazepine, theophylline, as it reduces their metabolism.

Isoniazid increases the blood concentration of valproic acid (monitoring of valproic acid concentration is necessary: adjustment of the dosing regimen may be required).

When isoniazid is combined with paracetamol, hepatotoxicity and nephrotoxicity increase.

Isoniazid reduces metabolic transformations and increases the blood concentration of alfentanil.

Cycloserine and disulfiram enhance the adverse central effects of isoniazid.

The combination of isoniazid with pyridoxine reduces the risk of developing peripheral neuritis.

Isoniazid should be combined with caution with potentially neuro-, hepato-, and nephrotoxic drugs due to the risk of increased side effects.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.