Pyrazinamide

Instruction manual

For medical use of the drug

Structure:

Active substance: pyrazinamide;

1 tablet contains pyrazinamide 500 mg in terms of 100% anhydrous substance;

excipients: povidone, crospovidone, microcrystalline cellulose, magnesium stearate.

Dosage form.

Tablets.

Basic physical and chemical properties: tablets of white or white with a yellowish tinge of color, round in shape, with a flat surface, with beveled edges and notch.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. anti-tuberculosis drugs. pyrazinamide. code atx j04a k01.

Pharmacological properties.

Pharmacodynamics

Pyrazinamide belongs to the pharmacotherapeutic group of second-line anti-TB drugs. The drug penetrates well into the foci of tuberculous lesions. Its activity does not decrease in the acidic environment of caseous masses, therefore it is often prescribed for caseous lymphadenitis, tuberculomas and caseous-pneumonic processes.

In the treatment with pyrazinamide, the development of resistance to tuberculosis mycobacteria is possible; therefore, it is prescribed, as a rule, in combination with other anti-TB drugs.

Pharmacokinetics

Pyrazinamide is almost completely absorbed in the digestive tract. When ingested 1 g of the drug, the plasma concentration is 45 μg / ml after 2 hours, 10 μg / ml after 15 hours. Pyrazinamide is hydrolyzed to the active metabolite - pyrazinic acid, and then to the inactive metabolite. The half-life of the drug with normal renal function is 9-10 hours. 70% of pyrazinamide is excreted by the kidneys. The drug is excreted within 24 hours, mainly in the form of metabolites.

Clinical characteristics.

Indications.

Treatment of all forms of tuberculosis (in combination with other tuberculostatic drugs).

Contraindications

• Hypersensitivity to pyrazinamide, to other components of the drug or to other drugs close to the chemical structure (ethionamide, isoniazid, niacin). severe liver failure. acute gout. asymptomatic hyperuricemia.

Interaction with other drugs and other types of interactions.

Alcohol: may increase the toxic effects of alcohol.

Isoniazid: a decrease in the concentration of isoniazid in the blood serum is possible, especially in patients with a slow metabolism of isoniazid.

In chronic destructive forms, it is recommended to combine pyrazinamide with rifampicin (pronounced effect) or ethambutol (better tolerance).

Drugs that block tubular secretion: a decrease in their excretion and an increase in toxic reactions are possible.

Ofloxacin, lomefloxacin: increased anti-tuberculosis effects.

Ethionamide: concomitant use increases the risk of liver damage, especially in diabetics. During treatment with a combination of these drugs, regular functional liver tests are necessary. If there are any signs of impaired liver function, treatment with such a combination of drugs should be discontinued.

Cyclosporin: a decrease in its metabolism, a decrease in serum levels and an immunosuppressive effect are possible. Patients who are treated with cyclosporine should monitor its serum levels after the initiation of pyrazinamide therapy and after its discontinuation.

Phenytoin: a possible increase in the concentration of phenytoin in the blood serum and, accordingly, the appearance of signs of phenytoin intoxication. If during the concomitant use of pyrazinamide and phenytoin there are side effects from the central nervous system (for example, ataxia, hyperreflexia, nystagmus, tremor), then the drugs should be discontinued, the concentration of phenytoin in the blood serum should be determined and the dose of phenytoin adjusted accordingly.

Drugs that promote the excretion of uric acid from the body (allopurinol, colchicine, probenecid, sulfinpyrazone): a decrease in their effectiveness is possible. This can increase serum uric acid levels in patients who are treated with pyrazinamide, therefore, doses of drugs that promote uric acid excretion from the body should be increased accordingly.

Allopurinol: may slow further conversion of pyrazinamide metabolites. The metabolism of pyrazinamide itself does not change significantly.

Zidovudine: a significant decrease in serum pyrazinamide levels and an increased risk of anemia are possible.

Hypoglycemic drugs: an increase in their effect is possible.

Pyrazinamide reduces the reliability of tests to determine ketones in urine using test strips (Acetest^® and ketostix^®), since it makes the color of the sample red-brown.

Pyrazinamide may interfere with determination of iron concentration in blood serum using a Ferrochem instrument^® II, because serum iron levels look less.

Features of the application.

Pyrazinamide should be used with caution in patients with impaired liver function and patients who have an increased risk of liver damage associated with taking the drug (for example, patients with alcoholism). during drug therapy, regular liver function tests should be performed every 2–4 weeks (thymol test, determination of bilirubin, study of glutamine-oxalic aminotransferase, alt and ast serum blood serum), as well as determination of uric acid in the blood. with changes in liver function, you should immediately stop using the drug.

To reduce the toxic effects of pyrazinamide, methionine, lipocaine, glucose, and vitamin B are prescribed.₁₂. Pyrazinamide can enhance the toxic effect of alcohol, so you should not drink alcohol while taking the drug.

In patients with porphyria, pyrazinamide can cause acute attacks of porphyria.

If any clinical signs or symptoms of liver failure occur, the drug should be discontinued.

Pyrazinamide delays the excretion of urate by the kidneys, which can lead to hyperuricemia, which may be asymptomatic. If hyperuricemia is accompanied by acute gouty arthritis, treatment with pyrazinamide should be discontinued.

In patients with renal failure, pyrazinamide can accumulate in the body.

Pyrazinamide should be used with caution in patients with diabetes mellitus because of the difficulty in maintaining the desired blood sugar concentration.

The choice of the dose of pyrazinamide for elderly patients requires caution and should begin in the lowest dose range (see "Dosage and Administration").

Use during pregnancy or lactation.

During pregnancy or breastfeeding, the drug is contraindicated.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

During treatment with the drug, adverse reactions occur from the nervous system, so during this period you should refrain from driving vehicles or other mechanisms.

Dosage and administration.

Take the tablets in a single dose after eating whole, drink with water. To calculate the daily dose, always use the ideal body weight.

The daily dose for adults and children from 15 years old is 20-30 mg / kg per admission.

Take 1-3 times a day, depending on tolerability. The maximum daily dose should not exceed 1.5 g.

Due to a possible decrease in kidney and liver function, elderly patients should use 15 mg / kg of body weight per day in doses close to the lower limit of the usual dose for adults.

The dose to patients with moderate impaired renal function is 12–20 mg / kg body weight per day. The use of pyrazinamide should be avoided in patients with creatinine clearance below 50 ml / min.

Patients on hemodialysis or peritoneal dialysis should be given the usual adult dose. It is advisable to apply 24 hours before dialysis.

If patients with impaired liver function use the usual dose, pyrazinamide accumulates in the body, so these patients need to use lower doses - 15 mg / kg body weight per day. Functional liver tests should be performed before starting pyrazinamide therapy and every 2–4 weeks during the use of the drug.

The duration of treatment depends on the course of the disease, the patients tolerance to the drug and is determined by the doctor (usually 6-8 months).

Children.

In this dosage form, pyrazinamide is prescribed for children from 15 years of age.

Overdose.

In some cases, impaired liver function and increased levels of transaminases. these disorders returned to normal after discontinuation of the drug.

Excitation, dyspeptic phenomena, impaired liver function, hyperuricemia, increased manifestations of adverse reactions were also observed.

Treatment. It is necessary to rinse the stomach, take activated charcoal, monitor liver function and determine the level of urate in the blood serum. The treatment is symptomatic. It is important that the patient consume a lot of fluids. Hemodialysis is effective.

Adverse Reactions

Skin and subcutaneous tissue: hyperemia, skin rash, urticaria, pruritus, photosensitivity, acne, toxic-allergic dermatitis.

Immune system: anaphylactoid reactions, angioedema, fever; in isolated cases - anaphylactic shock.

Digestive tract: dyspeptic symptoms, pain in the epigastrium, stomach, lack of appetite, nausea, vomiting, diarrhea, peptic ulcer, metallic taste in the mouth.

Hepatobiliary system: impaired liver function, increased levels of hepatic transaminases, bilirubin, thymol test, hepatomegaly; acute liver atrophy, which depends on the dose, jaundice.

Urinary system: interstitial nephritis; myoglobinuric renal failure due to rhabdomyolysis, dysuria, pain during urination.

Nervous system: dizziness, headache, sleep disturbance, irritability, depression; hallucinations, convulsions, confusion, peripheral neuropathy, paresthesia.

Cardiovascular system: hypotension, discomfort in the heart, sensation of heat, hyperemia of the face.

Blood and lymphatic system: thrombocytopenia, eosinophilia, anemia, sideroblastic anemia, vacuolization of red blood cells, porphyria, increased serum iron concentration, hypercoagulation, tendency to form blood clots, splenomegaly.

Musculoskeletal system and connective tissue: arthralgia, myalgia, rhabdomyolysis, gouty attacks, swelling of loam, stiffness in loam.

Respiratory: difficulty breathing, shortness of breath, dry cough.

Others: general weakness, malaise, hyperuricemia, pellagra.

Shelf life.

3 years.

Storage conditions.

In the original packaging at a temperature not exceeding 25 os.

Keep out of the reach of children.

Packaging.

10 tablets in a blister, 5 blisters in a pack; 120 tablets in a container and pack; 500 tablets in containers.

Vacation category.

On prescription.

Manufacturer.

Public Joint Stock Company “Scientific and Production Center“ Borshchag Chemical and Pharmaceutical Plant ”.

Limited Liability Company "Agrofarm".

The location of the manufacturer and the address of the place of business.

Ukraine, 03134, Kiev, st. peace, 17.

Ukraine, 08200, Kiev region, Irpin city, st. Central, 113-A.