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

A bacteriostatic broad-spectrum antibiotic is active against Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium, as well as Staphylococcus aureus and Staphylococcus epidermidis. The sensitivity of mycobacteria exceeds 90%. To terizidone are also sensitive: Enterococcus faecalis, Escherichia coli, Citrobacter spp., Enterobacter spp., Morganella morganii, Klebsiella pneumoniae and Pseudomonas aeruginosa.

Terisidone is a derivative of D-cyclisorin, competitively the enzyme that converts alanine to alanylalanine dipeptide is the main component of the microbial wall of mycobacteria.

Development of secondary resistance is rare. Cross-resistance with other anti-tuberculosis drugs is not observed.

Pharmacokinetics:

Absorption from the gastrointestinal tract - 70-90%, eating does not affect the rate of absorption. T_Cmax - 2-3 hours. Effective C_min: for mycobacteria tuberculosis is 10-40 mg / l, for staphylococci 8-32 mg / l, for gram-negative bacteria of clinical significance, 20-250 mg / l.

It is well distributed in tissues and body fluids (lungs, bile, ascites fluid, pleural effusion, synovial fluid, lymph, sputum). Penetrates CSF (80-100% of the serum concentration), a higher concentration in CSF is created by inflammatory changes in the meninges.

In the body, it is metabolized insignificantly. T_1/2 - 21 hours. It is excreted by the kidneys (60-70%) in unchanged form, a small amount is excreted intestine in unchanged form and in the form of metabolites.

Indications:

Tuberculosis (of various forms and localizations) in the complex therapy of drug-resistant forms of the disease.

ICD-10

I.A15-A19.A18 Tuberculosis of other organs

I.A15-A19.A17 Tuberculosis of the nervous system

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

I.A15-A19 Tuberculosis

Contraindications:

Hypersensitivity, including to cycloserine, organic diseases of the central nervous system (incl.atherosclerosis of cerebral vessels), epilepsy, mental disorders, alcoholism, pregnancy, lactation, children under 14 years.

Carefully:

The elderly, CHF, CRF.

Pregnancy and lactation:

Use in pregnancy is possible only if the expected benefit to the mother exceeds the potential risk to the fetus. Penetrates into breast milk (the concentration is close to the concentration in the plasma). If it is necessary to use terizidone, breastfeeding should be stopped.

Action category for the fetus by FDA - C

Dosing and Administration:

Inside, regardless of food intake: adults and children over 14 years of age and body weight less than 60 kg - 300 mg 2 times / day or 250 mg 3 times / day (600-750 mg / day); with a body weight of 60-80 kg -300 mg 3 times / day or 250 mg 4 times / day (900-1000 mg / day). Adults with a body weight of more than 80 kg - 600 mg 2 times / day (1200 mg / day). Accept for 3-4 months. With QC less than 30 ml / min dose and the frequency of intake is reduced.

Side effects:

From the nervous system: rarely - headache, dizziness, increased excitability, tremor, insomnia, a feeling of intoxication; very rarely - convulsions, depression, psychosis.

From the digestive system: abdominal pain, flatulence, diarrhea.

Other: allergic reactions, skin rash.

Overdose:

Symptoms: increased neurotoxicity (including convulsions), a violation of the function of the gastrointestinal tract.

Treatment: symptomatic, gastric lavage, Activated carbon, anticonvulsant, sedative drugs. Hemodialysis is effective.

Interaction:

Ethanol increases the risk and frequency of adverse reactions, incl. seizures.

When used simultaneously with ethionamide, there is an increased risk of side effects from the CNS (especially seizures).

Simultaneous use with isoniazid increases the incidence of dizziness, drowsiness.

When used simultaneously with anticoagulants, indirect effects enhance their effect. It is recommended to monitor prothrombin time and, if necessary, adjust the dose of anticoagulants.

With simultaneous application with phenytoin slows down its excretion and increases the risk of toxicity, dose adjustment may be required.

When used simultaneously with suxamethonium chloride (muscle relaxant) increases its effectiveness and the risk of adverse reactions. If necessary, adjust the dose.

With simultaneous use with cycloserine, an overdose of terizidone is possible.

Special instructions:

Terizidone can cause deficiency of cyanocobalamin and / or folic acid, it is necessary to conduct appropriate examination and treatment of the patient.

It should be monitored monthly blood and urine indicators, liver function (ALT, ACT, bilirubin).

Receiving terizidona against the background of alcohol increases the frequency of side effects, up to the development of seizures (avoid drinking alcohol).

Simultaneous use of caffeine can increase the risk of adverse reactions from the side of the central nervous system. To reduce the risk of such reactions, it is recommended to take vitamin B simultaneously₆.

In connection with the possibility of developing adverse reactions from the nervous system (depression, behavior change), it is necessary to monitor the patient's mental status.

During the treatment period it is necessary to refrain from driving vehicles and avoid practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Instructions

Terizidone (Terizidone)