Pyrazinamide - instructions for use, dose, side effects, contraindications

Pharmacodynamics:The drug is active against Mycobacterium tuberculosis. Has a bacteriostatic or bactericidal effect depending on the concentration. Keeps activity only in acidic medium (5.6 or lower), in particular in the foci of early active tuberculous inflammatory lesions. In the course of treatment, the development of resistance is possible, which can be prevented by using combinations with other anti-tuberculosis drugs.It is especially effective for newly diagnosed destructive tuberculosis, caseous lymphadenitis, tuberculoma and caseous-pneumonic processes. Reduces the excretion of uric acid and urate, can cause hyperglycemia.

Pharmacokinetics:Absorption from the gastrointestinal tract is rapid and almost complete. It is well distributed into most tissues and body fluids, including liver, lungs, kidneys, bile, spinal fluid (where a concentration of 87-105% is created corresponding to that in the plasma). The half-life is 9.5 hours (pyrazinamide with normal kidney function), 26 hours (pyrazinamide with chronic renal failure), 12 hours (pyrazinic acid with normal kidney function), 22 hours (pyrazinic acid in chronic kidney failure). The maximum concentration is observed after 1-2 hours (pyrazinamide), 4-5 hours (pyrazinic acid). Elimination by the kidneys (~ 3% in the form of unchanged substance, 33% in the form of pyrazinic acid, 36% - in the form of other unidentified metabolites within 72 hours).

Indications:Tuberculosis (in combination with other anti-TB drugs).

ICD-10

I.A15-A19 Tuberculosis

Contraindications:Hypersensitivity to pyrazinamide, isoniazid, ethionamide, nicotinic acid or other chemically related agents.

Carefully:Gout in history, hyperuricemia, impaired liver function.

Pregnancy and lactation:Recommendations FDA category C. The drug is not recommended during pregnancy and breastfeeding.

Dosing and Administration:Inside 15-30 mg / kg once a day or 50-70 mg / kg 2-3 times a week, depending on the treatment regimen.

In patients with HIV: inside 20-30 mg / kg per day during the first 2 months of treatment.

If the tolerance is unsatisfactory, the drug is prescribed in 2-3 doses.

Side effects:Blood: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.

Digestive system: nausea, vomiting, diarrhea, metallic taste in the mouth, exacerbation of peptic ulcer.

Urinary system: dysuria, interstitial nephritis.

Nervous system: headache, dizziness, sleep disorders, increased excitability, depression, hallucinations, convulsions, confusion.

Leather: skin itching, skin rashes, acne, photosensitivity.

Hypersensitivity: hives.

Patients hypersensitive to ethionamide, isoniazid, nicotinic acid and other chemically similar agents may also be hypersensitive to pyrazinamide.

Carcinogenicity / mutagenicity: in rats and mice at doses of 2 g / kg per day (40 times higher than the maximum for humans) and 0.5 g / kg per day (10 times higher than the maximum for humans) is not carcinogenic. It is not mutagenic in the Ames test, but it induces chromosomal aberrations in human lymphocyte culture.

Others: arthralgia, gouty arthritis, hepatotoxicity (usually with therapy in high doses - 40-50 mg / kg per day or for a long time), myalgia, hyperthermia.

Changes in laboratory tests: increased activity of hepatic transaminases, uric acid or serum iron.

Overdose:When an overdose develops a violation of liver function, an increase in the severity of side effects from the central nervous system. Treatment is symptomatic.

Interaction:Allopurinol, colchicine, probenecid, sulfinpyrazone - increasing the concentration of uric acid in the blood plasma and reducing the effectiveness of antidotal agents; it may be necessary to correct their dose when combined with pyrazinamide.

Rifampicin - the likelihood of developing a hepatotoxic effect.

Theophylline - a decrease in its concentration, half-life and an increase in clearance on the 5-7th day after the appointment of a combination of isoniazid, rifampicin, ethambutol and pyrazinamide.

Cyclosporine - a decrease in the concentration of cyclosporine in the blood plasma with the development of inadequate immunosuppression with parallel application; it is necessary to monitor the concentration of cyclosporine in the blood plasma.

Special instructions:During the treatment it is necessary to monitor liver function (AST, ALT - before treatment and every 2-4 weeks during therapy, however, an increase in the activity of enzymes in the blood plasma is not a harbinger of hepatitis and may return to normal with continued therapy), the concentration of uric acid in the plasma blood (during therapy, since it is possible to increase with the development of an acute attack of gout).

Instructions

Pyrazinamide (Pyrazinamidum)