Isoniazid
Isoniazid: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Drug interactions
- 11. Analogs
- 12. Terms and conditions of storage
- 13. Conditions for dispensing pharmacies
- 14. Reviews
- 15. Price in pharmacies
Latin name: Isoniazid
ATX code: J04AC01
Active ingredient: isoniazid (isoniazid)
Manufacturer: "AS-Pharm", "Tatkhimfarmpreparaty", "Bryntsalov-A", "PharmSintez", "Biochemist", "Biosintez", "Veropharm", "Rozpharm", "Akrikhin", OJSC "Moskhimfarmpreparaty them. N. A. Semashko "and others, Russia
Description and photo update: 2019-18-09
Isoniazid is an anti-tuberculosis drug.
Release form and composition
Dosage forms:
- Tablets (100, 200 or 300 mg - 10 pcs. In a blister strip, in a cardboard bundle 2, 5 or 10 packs, 50 or 100 pcs. In dark glass cans, in a cardboard bundle 1 can; 100 and 300 each mg - 20 pcs. in a blister, in a cardboard bundle 5 packs, 25 pcs. in a blister, in a carton pack 2 or 4 packs; 150 mg each - 10 pcs. in a blister, in a cardboard box 5 or 10 packs; 100 and 150 mg - 100, 500 or 1000 pcs. In polymer cans; 200 mg - 100, 500 or 1000 pcs. In polymer or polypropylene cans; 300 mg - 100 pcs. In cans polypropylene or polyethylene, in a cardboard bundle 1 can, 100, 500 or 1000 pieces each in polyethylene bags, in polymer cans 1 package);
- Solution for injection 10% (5 ml in ampoules - in a pack of 5, 10 or in a box of 10 ampoules; in a blister strip packaging 5 ampoules, in a cardboard bundle 2 packs).
The active substance is isoniazid:
- 1 tablet - 100, 150, 200 or 300 mg;
- 1 ml of solution - 100 mg.
Pharmacological properties
Pharmacodynamics
Isoniazid is an anti-tuberculosis drug and has a bacteriostatic effect. It belongs to prodrugs, since under the action of mycobacterial catalase-peroxidase, isoniazid is metabolized to form an active metabolite. The latter binds to the enoyl (acyl-transferring protein) reductase of fatty acid synthase I, thus disrupting the transformation of delta2-unsaturated fatty acids into mycolic acid. Mycolic acid is a branched-chain fatty acid that interacts with arabinogalactan (a polysaccharide) to form components of the cell wall of Mycobacterium tuberculosis.
Isoniazid is also an inhibitor of mycobacterial catalase-peroxidase, which helps to reduce the protective properties of the microorganism in relation to hydrogen peroxide and reactive oxygen species. Isoniazid demonstrates activity against certain strains of Mycobacterium kansasii (for infections provoked by this pathogen, it is recommended to determine the individual sensitivity to the drug).
Pharmacokinetics
After oral administration of a single dose of 300 mg Isoniazid, the maximum concentration of the active substance is reached after 1-2 hours and is 3-7 μg / ml. The substance binds to proteins insignificantly (by about 10%). The volume of distribution varies from 0.57 to 0.76 l / kg. Isoniazid is well distributed throughout the body, found in all tissues and fluids, including ascites, pleural and cerebrospinal. In high concentrations, the substance accumulates in sputum, saliva, lung tissue, muscles, liver and kidneys, and also penetrates the placental barrier and into breast milk.
Isoniazid is metabolized in the liver by acetylation to form inactive metabolites. In the liver, isoniazid is acetylated by N-acetyltransferase. The end product of the process is N-acetylisoniazide, which is then converted to monoacetylhydrazine and isonicotinic acid. Monoacetylhydrazine is characterized by a hepatotoxic effect due to the formation of an active intermediate metabolite with the participation of the cytochrome P 450 system by N-hydroxylation.
The rate of acetylation is determined by genetic factors. In patients whose acetylation process is slow, there is little N-acetyltransferase in the body.
Isoniazid is an inducer of the CYP2E1 isoenzyme. For fast acetylators, the half-life is about 0.5-1.6 hours, for slow ones, this parameter increases to 2-5 hours. In patients with renal insufficiency, the half-life is often prolonged to 6.7 hours. This indicator for children aged 1, 5–15 years old is 2.3–4.9 hours, and in newborns it reaches 7.8–19.8 hours, which is due to the imperfection of the acetylation process in this category of patients. Although the half-life value changes significantly due to the individual intensity of acetylation processes, its average value is 3 hours with oral administration of 600 mg and 5.1 hours with oral administration of 900 mg. With repeated administration, the half-life is reduced to 2–3 hours.
Isoniazid is excreted mainly in the urine: 75–95% of the drug is excreted within 1 day, mainly in the form of inactive metabolites - isonicotinic acid and N-acetylisoniazid. At the same time, the concentration of N-acetylisoniazide in fast acetylators is equal to 93% of the dose taken, while in slow ones it does not exceed 63%. In small quantities, isoniazid is excreted in the feces. During hemodialysis, the substance is removed from the blood (up to 73% of the drug during a five-hour session).
Indications for use
According to the instructions, Isoniazid is indicated for the prevention and treatment of all active forms of tuberculosis, including tuberculous meningitis (as part of a combination treatment).
For the prevention of tuberculosis, the drug is prescribed to children under the age of 4 years with a positive skin reaction to tuberculin (more than 10 mm), to persons in close contact with a patient with tuberculosis, to patients with a reaction to tuberculin of more than 5 mm and if non-progressive tuberculosis is indicated on radiological data.
Contraindications
The use of the drug is contraindicated in patients with the following pathologies:
- History of poliomyelitis, epilepsy and seizures;
- Impaired renal and / or liver function;
- Atherosclerosis.
Instructions for the use of Isoniazid: method and dosage
Isoniazid tablets are taken orally.
The solution is administered intramuscularly (in / m), intracavernosally and by inhalation.
The doctor sets the dose of Isoniazid and the period of treatment individually based on clinical indications, taking into account the age, nature and form of the disease.
Recommended dosage for adolescent and adult patients:
- Tablets: 300 mg 1 time per day or at the rate of 15 mg per 1 kg of patient weight per day 2-3 times a week (according to the treatment regimen);
- Solution: at the rate of 5 mg per 1 kg of body weight 1 time per day or 15 mg per 1 kg (also 1 time per day) 2-3 times a week.
The recommended dose for the use of the solution and Isoniazid tablets in children is 10-20 mg per 1 kg of body weight 1 time per day or 20-40 mg per 1 kg according to the therapy scheme 2-3 times a week;
The daily dose for intracavernous administration is 10-15 mg per 1 kg of body weight, for inhalation - 5-10 mg per 1 kg per day in 1-2 doses.
For adults, the maximum daily dose for each dosage form is 300 mg.
Side effects
The use of Isoniazid can cause side effects:
- From the side of the cardiovascular system: pain in the region of the heart;
- From the digestive system: medicinal hepatitis, nausea, vomiting;
- From the nervous system: dizziness, headache; rarely - sleep disturbances, euphoria, psychosis, peripheral neuritis;
- Allergic reactions: itching, skin rash;
- From the endocrine system: very rarely - menorrhagia in women, gynecomastia in men.
Overdose
Symptoms of an overdose of Isoniazid appear within 0.5-3 hours after administration. These include: dizziness, visual disturbances, visual hallucinations, blurry speech, nausea, and vomiting. In acute overdose, severe intractable seizures, acetonuria, severe metabolic acidosis, hyperglycemia, CNS depression, rapidly passing from a state of stupor to a coma, and respiratory distress syndrome are observed.
With a pronounced overdose of Isoniazid (taking doses of 80-150 mg / kg), insufficient treatment leads to a state of neurotoxication, most often resulting in a lethal outcome. With adequate treatment, the prognosis remains favorable.
If the drug was taken at a dose of more than 80 mg / kg, and there are no threatening symptoms, it is necessary to inject intravenous pyridoxine in the same dose. If the dose of isoniazid taken is unknown, then 5000 mg of pyridoxine is administered intravenously to adults for 30-60 minutes, and the antidote is administered to children at the rate of 80 mg / kg.
In the event of clinical symptoms, care must be taken to prevent aspiration of gastric contents, maintain the activity of the cardiovascular system and adequate pulmonary ventilation. If the dose of the drug taken is known, the same amount of pyridoxine is injected intravenously for 3-5 minutes. If the amount of the drug taken remains unknown, then adults are injected intravenously with pyridoxine in the amount of 5000 mg, for children - in the amount of 80 mg / kg. If the seizure continues, the pyridoxine dose is re-administered. In isolated cases, an antidote dose of more than 10,000 mg is required.
In case of an overdose of Isoniazid, the maximum safe dose of pyridoxine is unknown. If pyridoxine does not give a therapeutic effect, diazepam is prescribed.
In a state of overdose, the level of urea, glucose, electrolytes and the partial pressure of gases in the blood should be monitored. When diagnosing metabolic acidosis, sodium bicarbonate can provoke an increase in hypercapnia (constant monitoring of the condition is necessary). If acidosis and seizures are not relieved by sodium bicarbonate, diazepam, and pyridoxine, dialysis is necessary.
special instructions
Isoniazid should not be prescribed at a dose of more than 10 mg per 1 kg of patient weight in severe forms of arterial hypertension and / or cardiopulmonary insufficiency, widespread atherosclerosis, coronary heart disease, diseases of the nervous system, psoriasis, bronchial asthma, myxedema, eczema in the acute phase.
When prescribing a dose of the drug, one should take into account the degree of influence of genetic factors on acetylation of isoniazid in the liver; for this, it is necessary to determine the rate of inactivation by its content in urine and blood. For patients with a high rate of inactivation, it is advisable to prescribe higher doses of the drug.
To prevent the rapid development of Koch's bacillus resistance, the use of isoniazid is combined with other anti-tuberculosis drugs.
After injection of the drug, the patient should be kept in bed for 1-1.5 hours.
To reduce side effects, isoniazid is prescribed in combination with glutamic acid (orally), pyridoxine (orally or intramuscularly), thiamine (intramuscularly).
Influence on the ability to drive vehicles and complex mechanisms
Drivers and operators working with complex mechanisms need to take into account the likelihood of side effects from the central nervous system, which can impair the speed of reaction and concentration.
Application during pregnancy and lactation
During pregnancy, Isoniazid is contraindicated in a dose of more than 10 mg / kg per day. When using the drug in a daily dose of less than 10 mg / kg of body weight, it should be borne in mind that the substance penetrates the placental barrier and can provoke the development of hemorrhages (due to vitamin K hypovitaminosis), hypospadias and myelomeningocele, as well as a delay in the psychomotor development of the fetus. Isoniazid passes into breast milk, therefore, due to the risk of developing peripheral neuritis and hepatitis in a child, breastfeeding should be discontinued or the drug should be discontinued.
Drug interactions
When combined with paracetamol, rifampicin, the likelihood of developing hepatotoxic effects increases, especially in patients with impaired liver function.
Isoniazid, when taken simultaneously, suppresses the metabolism of phenytoin and carbamazepine, this increases the level of their concentration in blood plasma and toxic effects.
Analogs
Analogues of Isoniazid are: Isoniazid-Akos, Isoniazid-Ferein, Isoniazid-Darnitsa, Isoniazid-N. S., Isosid 200, Nidrazid, Rimicid, Tubazid.
Terms and conditions of storage
Store: tablets - in a dry, dark place, solution - in a dark place at a temperature of 1-10 ° C. Keep out of the reach of children.
Shelf life: tablets - 6 years, solution - 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Isoniazid
Reviews of Isoniazid indicate that after the start of the course of therapy in the first days of treatment, patients often complained of impaired coordination, nightmares, insomnia, severe headaches, and rapid fatigue. However, when the drug was combined with vitamin B 6, the side effects became less pronounced. Quite often, the causative agent of tuberculosis has shown resistance to this drug. Nevertheless, experts speak positively about Isoniazid, considering it a fairly effective drug against tuberculosis.
Isoniazid price in pharmacies
The price of Isoniazid in the form of tablets averages 42–83 rubles (the package includes 100 pcs.). Solution for injection 10% can be bought for about 25–48 rubles (the package includes 10 ampoules).
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
