Isoniazid + Pyrazinamide + Rifampicin + Etambutol - instructions for use, dose, side effects, contraindications

Inhibits the enzymes necessary for the synthesis of mycolic acids, which are the main structural fragments of the cell walls of mycobacterium tuberculosis.

The most intensive synthesis of mycolic acids is carried out in growing cells, so isoniazid has a bactericidal action on them, and bacteriostatic action on mature cells.

The high selectivity of the chemotherapeutic effect of isoniazid is due to the fact that there are no mycolic acids in the tissues of the macroorganism, as well as in other microorganisms.

Pyrazinamide

In the body it turns into pyrazinic acid, which is active only in acidic medium (foci of caseous decay).Prevents the synthesis of mycolic acid, the main substrate of mycobacterium tuberculosis membranes.

Rifampicin

Semisynthetic antibacterial agent of bactericidal action. Selectively inhibits the DNA-dependent RNA polymerase of mycobacterium tuberculosis and leprosy.

Ethambutol

Blocking the incorporation of mycolic acids into the cell wall, suppresses synthesis of mycobacterium membrane. Operates bacteriostatically in relation to Mycobacterium tuberculosis, M. bovis and nontuberculous mycobacteria (M. kansasii).

Pharmacokinetics:

Isoniazid

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration in blood plasma is achieved in 1-4 hours. The connection with plasma proteins is from 1 to 10%.

Therapeutic effect develops after the reception. Metabolism in the liver by acetylation to inactive metabolites, penetrates the placental barrier, is excreted in breast milk.

The rate of acetylation of the drug is genetically determined, so the half-life of isoniazid varies. Half-life for "fast acetylators" is 1 hour, for "slow acetylators" - 3 hours.Elimination by the kidneys.

Pyrazinamide

After oral administration, the empty stomach is completely absorbed in the gastrointestinal tract. The maximum concentration of pyrazinic acid in the blood plasma is reached after 2 hours. The connection with plasma proteins is 10-20%.

Metabolism in the liver.

The half-life is 8-9 hours. Elimination by the kidneys.

Rifampicin

After oral administration, up to 98% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved in 2-3 hours. The connection with plasma proteins is 84-91%.

Metabolism in the liver. Penetrates through blood-brain and placental barriers, excreted in breast milk.

The half-life is 2.5-5 hours. Elimination with feces and kidneys.

Ethambutol

After oral administration, an empty stomach is absorbed up to 80% in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 2 hours. The connection with plasma proteins is 10-40%.

Metabolism in the liver.

The half-life is 3.3-3.5 hours. Elimination with feces and kidneys.

Indications:

It is used for the treatment of pulmonary tuberculosis and extrapulmonary forms of tuberculosis of the initial stage.

ICD-10

I.A15-A19.A15 Tuberculosis of respiratory organs, confirmed bacteriologically and histologically

I.A15-A19.A16 Tuberculosis of respiratory organs, not confirmed bacteriologically or histologically

Contraindications:

Peptic ulcer of the stomach and duodenum, cardiovascular insufficiency, epilepsy, propensity to convulsive seizures, diseases of the eyes, violations of the liver and kidneys, age to 13 years, pregnancy and lactation, individual intolerance.

Carefully:

Atherosclerosis, psoriasis, bronchial asthma, diseases of the nervous system, eczema in the phase of exacerbation, myxedema.

Pregnancy and lactation:

Recommendations for FDA - Category C. Contraindicated in pregnancy and lactation.

Dosing and Administration:

Inside for 1 hour before meals. Dosage is calculated by the amount of rifampicin, the amount of which should correspond to 10 mg / kg of body weight, but not more than 5 tablets in one dose.

The highest daily dose: 5 tablets.

The highest single dose: 5 tablets.

Side effects:

Isoniazid

Central and peripheral nervous system: memory disorders, insomnia, mental disorders disorders, euphoria, peripheral neuritis, muscle twitching.

The cardiovascular system: pain in the heart.

Digestive system: medicinal hepatitis.

Dermatological reactions: itching, skin rash.

Sense organs: optic neuritis - blurred vision or loss of vision.

Reproductive system: gynecomastia, menorrhagia.

Allergic reactions.

Pyrazinamide

Central and peripheral nervous system: dizziness, headache, depression, increased excitability, sleep disorders, convulsions, hallucinations.

Hemopoietic system: thrombocytopenia, porphyria, hypercoagulation.

Digestive system: a sensation of metallic taste in the mouth, vomiting, diarrhea.

Musculoskeletal system: myalgia, arthralgia, rarely - gouty arthritis.

Dermatological reactions: acne, photosensitivity.

urinary system: interstitial nephritis.

Allergic reactions.

Rifampicin

Central and peripheral nervous system: headache, disorientation, hallucinations.

Respiratory system: bronchospasm.

Hemopoietic system: eosinophilia.

Digestive system: nausea, vomiting, decreased appetite, diarrhea, hepatitis, enterocolitis.

Dermatological reactions: a rash.

Sense organs: impaired vision.

Allergic reactions.

Ethambutol

Central and peripheral nervous system: confusion, headache, hallucinations, disorientation, peripheral neuropathy.

Digestive system: sensation of metallic taste in the mouth, anorexia, nausea, vomiting, gastralgia.

Dermatological reactions: dermatitis, rash.

Sense organs: retrobulbar neuritis with decreased visual acuity, narrowing of the visual fields, violation of color perception (red and green), central or peripheral scotoma.

Allergic reactions.

Overdose:

Metabolic acidosis, neurotoxic effect: dysarthria, lethargy, disorientation, hyperreflexia, convulsions, coma.

Treatment is symptomatic. Effective hemodialysis.

Interaction:

Strengthens the action indirect hemocoagulants.

Inhibits the metabolism of benzodiazepines, phenytoin and theophylline.

Simultaneous use with paracetamol and other hepatotoxic substances increases the risk of toxic hepatonecrosis.

Antatsidnye means slow down and reduce the absorption of isoniazid in the intestine, it is recommended to take them with an interval of 1 hour.

With the simultaneous use of certain fish species (tuna, sardinella) and cheeses (Swiss), there may be a hyperemia of the skin, itching, headache due to the isoniazid suppression of monoamine oxidase and diaminoxidase activity in the blood plasma and a violation of the metabolism of histamine and tyramine.

Rifampicin reduces the effects of anticoagulants, hormonal contraceptives, antiarrhythmics, ketoconazole, cyclosporine, phenytoin, chloramphenicol, glucocorticosteroids, enalapril, slow calcium channel blockers, cimetidine.

Opiates, antacids, ketoconazole reduce the bioavailability of rifampicin.

Aluminum hydroxide reduces the absorption of ethambutol.

Special instructions:

It is recommended to use reliable contraceptive methods during taking the drug.

In the treatment it is not recommended to drive vehicles and work with moving mechanisms.

Instructions

Isoniazid + Pyrazinamide + Rifampicin + Ethambutol (Isoniazidum + Pyrazinamidum + Rifampicinum + Aethambutolum + Pyridoxinum)