Isoniazid

General characteristics. Structure:

Active ingredient: isoniazid.

Pharmacological properties:

Antituberculous remedy of the I row. Has bactericidal effect. The isoniazid is active in the relation out of - and intracellular Mycobacterium tuberculosis, first of all concerning actively sharing. The exact mechanism of its action is unknown. It is supposed that it is connected with suppression of synthesis of the mikoliyevy acids which are a part of a cell wall of mycobacteria.

Pharmacokinetics. After intake it is quickly absorbed from a GIT. At reception with food absorption and bioavailability decrease. It is widely distributed in all fabrics and liquids of an organism. Linkng with proteins of plasma very low (0-10%). It is metabolized in a liver. A small amount - with a stake is removed with urine.

Indications to use:

Treatment of all forms of active tuberculosis, including tubercular meningitis (as a part of a combination therapy). Prevention of tuberculosis at the persons which are in close contact with TB patients; at persons with positive skin reaction (more than 5 mm) to tuberculine and the radiological data indicating not progressing tuberculosis; at children 4 years with positive reaction to tuberculine (more than 10 mm) and the increased risk of dissimination are younger.

Route of administration and doses:

Inside, in oil, in/in it is, vnutrikavernozno, inhalation. The mode of dosing and duration of treatment are established individually, depending on a form of a disease and portability of treatment. Inside, the adult appoint 300 mg 2–3 times a day, the maximum single dose — 600 mg, daily — 900 mg. To children — 5–15 mg/kg/days, frequency rate of reception — 1–2 times a day, the maximum daily dose — 500 mg.

In oil enter 5–12 mg/kg, frequency rate of use — 1–2 times a day.

In/in (during 30–60 c) on 10–15 mg/kg/days; a course — 30–150 injections. After introduction it is necessary to observe a bed rest during 1–1,5 h.

Vnutrikavernozno: 10% solution in a dose of 10-15 mg/kg/days, preferential adult, at a bakteriovydeleniya and a preparation for surgery. Cavities and fistulas wash out 1–2% aqueous solution of 1 times a day, in a dose of 50-200 mg. It is inhalation: 10% solution in a dose of 5-10 mg/kg/days in 1–2 introductions, daily within 1–6 months.

Features of use:

Heavy and sometimes the fatal hepatitis associated with therapy by an isoniazid can develop even in several months of treatment. The risk of developing of hepatitis depends on age; approximate frequency: 1/1000 people are aged younger than 20 years, 3/1000 in an age group 20–34 years, 12/1000 in an age group of 35-49 years, 23/1000 in an age group 50–64 years, 8/1000 65 years are aged more senior. The risk of hepatitis increases at daily alcohol intake. There are no exact data on a share of fatal outcomes at an isoniazid - the induced hepatitis, but, according to U.S. Public Health Service Surveillance Study (PDR, 2005), among 13838 patients receiving an isoniazid 8 lethal outcomes from 174 cases of hepatitis were recorded. In this regard the patients receiving an isoniazid should be inspected monthly carefully. Increase in level of serumal transaminases is observed approximately at 10–20% of patients, usually in the first several months of therapy. Despite therapy continuation, indicators are returned to norm, but the progressing liver dysfunction in certain cases develops. Patients have to be instructed about the immediate address to the doctor at emergence of any prodromal symptom of hepatitis (fatigue, weakness, an indisposition, anorexia, nausea or vomiting). If symptoms and signs of an abnormal liver function (including increase in activity of hepatic transaminases) are found, at once cancel drug since at reception continuation perhaps more serious damage of a liver. Resume treatment after normalization of indicators.

At emergence of symptoms of a vision disorder against the background of treatment it is required immediate, and further — regular ophthalmologic inspection (for timely diagnosis of damage of an optic nerve).

During treatment it is necessary to avoid alcohol intake.

Treatment by an isoniazid should be combined with B6 vitamin reception (in 60–100 mg in 2 h after an isoniazid injection, or 100–150 mg/days in oil in 30 min. after an injection), glutaminic acid (1–1,5 g/days), B1 vitamin (1 ml of 5% in oil of solution of Thiamini chloridum or 1 ml of 6% of solution of Thiamini bromidum) and the ATP sodium salt for the purpose of prevention of peripheral neuropathy and other by-effects from a nervous system.

It is necessary to observe the greatest possible intervals between introductions of an isoniazid and streptomycin, to take an isoniazid not less than for 1 h before reception of antacids.

Consumption of cheese (Swiss, etc.), fishes (a tuna, etc.) and some other products against the background of reception of an isoniazid can be followed by feeling of heat or a fever, reddening and an itch of skin, heartbeat, perspiration, a headache, dizziness owing to disturbance by an isoniazid of metabolism of tyramine and a histamine.

Side effects:

From a nervous system and sense bodys: a headache, dizziness, irritability, an insomniya, encephalopathy, euphoria, amnesia, neuritis or an atrophy of an optic nerve, peripheral neuritis and a polyneuritis, paresthesia, paralysis of extremities, spasms, including generalized, increase of convulsive attacks at patients with epilepsy, intoksikatsionny psychosis.

From cardiovascular system and blood (a hemopoiesis, a hemostasis): heartbeat, increase in the system and pulmonary ABP, strengthening of ischemia of a myocardium at elderly patients, pain in heart, stenocardia; an agranulocytosis, hemolysis (at deficit glyukozo-6-fosfatdegidrogenazy), sideroblastny or aplastic anemia, thrombocytopenia.

From bodies of a GIT: dryness in a mouth, nausea, vomiting, a hyperbilirubinemia, prodromal symptoms of hepatitis (appetite loss, nausea or vomiting, unusual fatigue or weakness), increase in activity of hepatic transaminases, toxic hepatitis.

From urinogenital system: gynecomastia, menorrhagia, dysmenorrhea.

Allergic reactions: eosinophilia, skin rash.

Others: muscular twitchings, an atrophy of muscles, fever, "cushingoid", a hyperglycemia, fever, phlebitis (at in introduction).

Interaction with other medicines:

At simultaneous use with rifampicin the risk of development of a hepatotoxic action increases (especially at patients with abnormal liver functions).

At simultaneous use with paracetamol the risk of development of a hepatotoxic action since the isoniazid induces P450 cytochrome that leads to increase in maintenance of toxic metabolites of paracetamol increases.

At simultaneous use of an isoniazid with carbamazepine or Phenytoinum metabolism of the last is suppressed that leads to increase in their concentration in a blood plasma and to strengthening of toxic action.

Contraindications:

Hypersensitivity, including to Etioniamidum, Pyrazinamidum, Niacinum (niacin) and to others similar on chemical structure HP, epilepsy, tendency to convulsive attacks, poliomyelitis (including in the anamnesis), heavy hepatonephric insufficiency, mental diseases, the expressed atherosclerosis, diseases visual and peripheral nerves, the toxic hepatitis in the anamnesis connected with reception of an isoniazid or its derivatives (Ftivazidum, metazid, Opiniazidum), phlebitis (in/in introduction).

Storage conditions:

List B.: In the dry, protected from light place. Period of validity of 6 years.

Issue conditions:

According to the recipe