Isoniazid

When ATH:
J04AC01

Characteristic.

Anti-TB drugs. Isonicotinic acid hydrazide, a structural analog of vitamin B₆. The white crystalline powder;, bitter taste. Sensitive exposure to air and light. Easily soluble in water, difficult — in ethyl alcohol, very little in chloroform, practically insoluble in ether, benzene. pH 1% aqueous solution of 5,5 to 6,5. Molecular weight 137,14.

Pharmacological action.
Antiphthisic, Antibacterial, bactericide.

Application.

Tuberculosis (any location, in adults and children, in combination with other drugs); primary and secondary chemoprophylaxis infected and contact people on tuberculosis.

Contraindications.

Hypersensitivity, incl. to ethionamide, pirazinamidu, Niacin (a nicotinic acid) and other similar chemical structure PM, epilepsy, propensity to seizures, polio (incl. history), severe renal and hepatic failure, mental illness, expressed atherosclerosis, diseases of the optic nerve and peripheral, toxic hepatitis in history, associated with isoniazid or its derivatives (ftivazid, metazid, opiniazid), phlebitis (in / introduction).

Restrictions apply.

Doses above 10 mg / kg / day: pregnancy, lactation, porphyria, a history of psychosis, alcoholism, pulmonary heart disease stage III, hypertension stage II and III, CHD, widespread atherosclerosis, nervous system diseases, bronchial asthma, psoriasis, eczema (exacerbation), gipotireoz, acute hepatitis, cirrhosis of the liver, chronic renal failure.

Pregnancy and breast-feeding.

In pregnancy, the use is possible only on strict conditions, in comparing the expected benefits to the mother and the risk to the fetus (It should be applied in doses up to 10 mg / kg / day).

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

At the time of treatment is recommended not to breastfeed.

Side effects.

From the nervous system and sensory organs: headache, dizziness, irritability, insomnia, encephalopathy, euphoria, amnesia, neuritis or atrophy of the optic nerve, peripheral neuritis and polyneuritis, paraesthesia, paralysis of limbs, convulsions, incl. Generalized, increased frequency of seizures in patients with epilepsy, substance-induced psychosis.

Cardio-vascular system and blood (hematopoiesis, hemostasis): heartbeat, increase in systemic and pulmonary blood pressure, increased myocardial ischemia in elderly patients, precordial pain, angina; agranulocytosis, gemoliz (in the definition, glucose-6-fosfatdegidrogenazы), sideroblastic, or aplastic anemia, thrombocytopenia.

From the digestive tract: dry mouth, nausea, vomiting, giperʙiliruʙinemija, prodromal symptoms of hepatitis (loss of appetite, nausea or vomiting, unusual tiredness or weakness), increase in liver transaminases, toxic hepatitis.

With the genitourinary system: gynecomastia, menorragija, dysmenorrhoea.

Allergic reactions: eozinofilija, skin rash.

Other: vellication, amyotrophy, fever, 'Kuşingoid, giperglikemiâ, fever, phlebitis (at / in the introduction).

Cooperation.

Antacids, especially aluminum-, reduce the absorption of isoniazid. Strengthens (mutually) the effect of other anti-TB drugs. At simultaneous reception with streptomycin slows excretion by the kidneys of both drugs, rifampitsinom with — increases the risk of Hepatotoxicity. Liver toxicity is potentiated by isoflurane. Vitamin B₆ glutamic acid and reduce the likelihood of side effects, MAO inhibitors-increase. It inhibits the metabolism, increases plasma concentration and increases the effect of indirect anticoagulants, teofillina, benzodiazepines, karʙamazepina, ethosuximide; reduces the concentration of ketoconazole. It enhances the toxic effects of cycloserine, disulьfirama, enflurane, phenytoin, paracetamol and another LS, providing hepato- and neurotoxic effects.

Overdose.

Symptoms: slackness, dizziness, nausea, vomiting, impaired vision and hearing, heteroptics, gibberish, disorientation, hyperreflexia, respiratory depression, metabolic acidosis, convulsions, stupor, coma, giperglikemiâ, glycosuria, ketonwrïya.

Treatment: IVL, I / short acting barbiturate, w / w vitamin B₆ (dose, equivalent to the dose of isoniazid; if the dose is unknown, administered by 5 g vitamin B₆ as 5% aqueous solution every 5-30 minutes prior to the termination of seizures or recovery of consciousness), sodium bicarbonate (the development of metabolic acidosis), diazepam, thiopental sodium, After the cessation of seizures — gastric lavage, administration of activated charcoal and laxatives, osmotic diuretics, diurez, hemodialysis; in case of impossibility of the kidney — peritoneal dialysis simultaneously with enhanced diurezom.

Dosing and Administration.

Inside, / m, I /, vnutrykavernozno, inhalation. The dosage regimen and duration of treatment set individually, depending on the form of the disease and tolerability. Inside, Adults appoint 300 mg 2-3 times a day, The maximum single dose - 600 mg, daily - 900 mg. Children 5-15 mg/kg/day, the reception frequency is 1-2 times a day, The maximum daily dose - 500 mg.

In/m imposed on 5-12 mg/kg, frequency of use is 1-2 times a day.

B / (30-60 with) 10-15 mg / kg / day; the course is 30-150 infusions. After the introduction, you must observe bed rest for 1-1, 5 h.

Vnutrykavernozno: 10% solution at a dose of 10-15 mg / kg / day, mostly adults, bakteriovydelenii and preparation for surgery. Cavities and fistulae washed 1-2% aqueous solution 1 once a day, at a dose of 50-200 mg. Inhalation: 10% solution of 5-10 mg / kg / day administration 1-2, daily for 1-6 months.

Precautions.

Severe and sometimes fatal hepatitis, associated with isoniazid therapy, It may develop even after many months of treatment. The risk of hepatitis depends on the age; sampling frequency: 1/1000 People under the age of 20 years, 3/1000 in the age group 20-34 years, 12/1000 in the age group 35-49 years, 23/1000 in the age group 50-64 years, 8/1000 the age 65 years. The risk of hepatitis is increased with daily alcohol consumption. Precise data on the percentage of fatalities in the isoniazid-induced hepatitis is not, but, According to U.S. Public Health Service Surveillance Study (PDR, 2005), among 13838 patients, poluchavshikh isoniazid, It was recorded 8 deaths from 174 cases of hepatitis. Therefore patients, poluchayushikh isoniazid, should be carefully examined on a monthly basis. Increased serum transaminases observed in approximately 10-20% of patients, usually within the first few months of treatment. Despite continued therapy, parameters return to normal, but in some cases developed progressive liver dysfunction. Patients should be instructed to immediately appeal to the doctor when you see any «symptom of hepatitis (fatigue, weakness, malaise, anorexia, nausea or vomiting). If signs and symptoms of liver dysfunction (incl. increase in liver transaminases) found, drug immediately overturned, tk. while continuing to receive perhaps more serious liver damage. Renew treatment after normalization.

When symptoms of blurred vision during treatment requires immediate, and then regular ophthalmologic examination (for the timely diagnosis of lesions of the optic nerve).

During treatment should avoid alcohol.

Treatment with isoniazid should be combined with vitamin intake₆ (inside the 60-100 mg every 2 hours after injection of isoniazid, or / m 100-150 mg / day via 30 min after injection), glutamic acid (11.5 g / day), vitamin B₁ (/ m 1 ml 5% or thiamine chloride solution 1 ml 6% solution of thiamine bromide) and the sodium salt of ATP to prevent peripheral neuropathy or other side effects in the nervous system.

Observe the maximum possible interval between the introduction of isoniazid and streptomycin, taking isoniazid at least 1 hours before antacids.

Eating cheese (Swiss and others.), fish (tuna and others.) and some other products while taking isoniazid may be accompanied by hot flashes or chills, redness and itching of the skin, heartbeat, sweating, headache, dizziness due to violation of isoniazid metabolism of tyramine and histamine.

Cooperation