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

Composition:Composition per one tablet:
active substance: pyrazinamide 0.5 g.
Excipients: microcrystalline cellulose, potato starch, povidone (Kollidon 25), croscarmellose sodium (impellose), magnesium stearate.

Description:Tablets are white or almost white, flat-cylindrical with a facet and a risk.

Pharmacotherapeutic group:Anti-tuberculosis drug.

ATX: & nbsp

J.04.A.K.01 Pyrazinamide

Pharmacodynamics:Anti-tuberculosis drug of the II series.It acts on intracellularly located mycobacteria. Has a bacteriostatic or bactericidal effect depending on the concentration and sensitivity of the microorganism. More active on tuberculostatic activity than paraaminosalicylic acid (PASK), although inferior to isoniazid, streptomycin, rifampicin. It operates on mycobacteria, resistant to other anti-tuberculosis drugs of the II series. The drug penetrates well into the centers of tuberculous lesion. Its activity does not decrease in the acidic environment of caseous masses, and therefore it is often prescribed for caseous lymphadenitis, tuberculomas and caseous-pneumonia processes.

Pharmacokinetics:Pyrazinamide well absorbed from the gastrointestinal tract. After oral administration of a dose of 500 mg, the peak concentration of pyrazinamide in plasma in adults within 9-12 μg / ml is achieved within 2 hours, 7 μg / ml after 8 hours and 2 μg / ml after 24 hours. Pyrazinamide penetrates into tissues and body fluids, including the liver, lungs, brain, cerebrospinal fluid. Connection with blood plasma proteins - 10-20%. Time to reach the maximum concentration in the blood plasma (TCmax) - 1-2 hours.
Metabolised in the liver, where an active metabolite (pyrazinic acid) is first formed, which later becomes an inactive metabolite - 5-hydroxypyrazinic acid. The half-life (T1 / 2) is 8-9 hours. It is excreted by the kidneys: unchanged, 3%, pyrazinic acid 33%, and other metabolites 36%.

Indications:In combination with other anti-tuberculosis drugs are prescribed in the following cases:
- pulmonary tuberculosis;
- tuberculous meningitis;
- tuberculosis of bones;
tuberculosis of urogenital organs.

Contraindications:- individual intolerance;
- liver disease;
- gout;
Hyperuricemia;
- Pregnancy, lactation;
- Children's age up to 3 years (for this dosage form).

Dosing and Administration:The drug is used inside, during or after a meal, once a day, preferably at breakfast with a little water.
Adults appoint 25-30 mg / kg body weight, which corresponds to those with a body weight of less than 50 kg - 1.5 g and for individuals with a body weight of more than 50 kg - 2 g.
The maximum daily dose is 2.5 g.
In case of unsatisfactory portability pyrazinamide appoint 2-3 reception.
In elderly and elderly people, the drug should be administered every other day at a dose of 15 mg / kg.
Children are prescribed 15-20 mg / kg once a day (maximum dose of 1.5 g per day).
Pyrazinamide is used in combination with aminoglycosides (streptomycin or kanamycin in a dose of 15 mg / kg), isoniazid (10 mg / kg), rifampicin (10 mg / kg).
The course of treatment is 3 months or more.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, "metallic" taste in the mouth, abnormal liver function (anorexia, pain of the liver, hepatomegaly, jaundice, yellow atrophy of the liver); exacerbation of peptic ulcer.
From the central nervous system: dizziness, headache, sleep disturbances, increased excitability, depression; in some cases - hallucinations, convulsions, confusion.
From the genitourinary and urinary system: dysuria, interstitial nephritis.
From the musculoskeletal system: arthralgia, myalgia.
On the part of the organs of hematopoiesis and the system of hemostasis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, hypercoagulation, splenomegaly.
Allergic reactions: skin rash, hives, photosensitivity.
Other: fever, hyperuricemia, exacerbation of gout, increased serum iron concentrations.

Overdose:Symptoms: Dysfunction of the liver, increased severity of side effects from the central nervous system.
Treatment: symptomatic.

Interaction:Pyrazinamide are combined with other antituberculosis drugs. In particular, with chronic destructive forms it is recommended to combine it with rifampicin (pronounced effect) or ethambutol (better tolerability). The likelihood of developing a hepatotoxic effect of the drug is increased when combined with rifampicin. Possible development of hypoglycemia in patients with diabetes mellitus. With simultaneous application with probenecid, a decrease in excretion and, consequently, an increase in toxic reactions is possible.

Special instructions:It is necessary at least once a month to monitor the activity of alanine aminotransferase and the content of uric acid in the blood.

Form release / dosage:Tablets 500 mg.

Packaging:For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.
5 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:In the dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

Shelf life:2 years.
Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N003855 / 01

Date of registration:25.11.2009

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp29.07.2015

Illustrated instructions

Instructions

Pyrazinamide (Pyrazinamide)