Included in the formulation
АТХ:J.04.A.K.03 Terizidone
A.11.H.A.02 Pyridoxine (vitamin B6)
Pharmacodynamics:Terizidone
Bacteriostatic broad-spectrum antibiotic, D-cycloserine derivative. Competitively blocks enzymes that incorporate alanine into alanyl-alanine dipeptide, the main component of the mycobacterial wall. It is active against Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium avium, as well as Staphylococcus aureus and Staphylococcus epidermidis. Terisidone is also sensitive to Enterococcus faecalis, Escherichia coli, Citrobacter, Enterobacter, Morgariella morganii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Cases of development of secondary resistance are rare. Cross-resistance with other anti-tuberculosis drugs is not observed.
Pyridoxine
It participates in the metabolism, it is necessary for the normal functioning of the central and peripheral nervous systems. Entering the body, phosphorylated, converted to pyridoxal-5-phosphate.Acting as coenzyme, it participates in the metabolism of amino acids and glycogen, in the synthesis of nucleic acids, hemoglobin, sphingomyelin and other sphingolipids, in the synthesis of mediators (serotonin, dopamine, GABA). Has a neuroprotective effect. Reduces the neurotoxic effect of anti-tuberculosis drugs.
Pharmacokinetics:Terizidone: after peroralnogo application is almost completely absorbed from the digestive tract (70-90%). Cmax in plasma is achieved after 2-4 hours. Food intake does not affect the rate of absorption. The level of effective Cmin for mycobacteria tuberculosis is 10-40 mg / l, for staphylococci 8-32 mg / l, for gram-negative bacteria having a clinical value of 20-250 mg / l.
It spreads in tissues and body fluids, lungs, bile, ascitic fluid, pleural effusion and synovial fluid, lymph and sputum.
It penetrates well into the CSF (80-100% of the serum concentration), a higher concentration in the cerebrospinal fluid is created by inflammatory changes in the meninges.
When ingested high concentrations of terizidone are found in the blood and urine, which allows it to be used to treat infections of the urinary tract, incl. chronic forms.
It is excreted by the kidneys, the half-life period is 21-24 hours. From 60 to 70% is excreted unchanged by glomerular filtration; a small amount is excreted through the intestine and a small part in the form of metabolites. With renal failure, the elimination half-life increases to 72 hours.
Pyridoxine: after administration is rapidly absorbed throughout the small intestine, more is absorbed in the jejunum. Metabolised in the liver with the formation of pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxalphosphate 90% is associated with plasma proteins.
It penetrates well into all tissues; accumulates mainly in the liver, less - in the muscles and the central nervous system. Penetrates through the placenta, is secreted with breast milk. The half-life is 15-20 days. It is excreted by the kidneys (with intravenous injection - 2% with bile), and also during hemodialysis.
Indications:Tuberculosis (various forms and localizations) in the complex treatment of drug-resistant forms of tuberculosis.
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
I.A15-A19.A17 Tuberculosis of the nervous system
I.A15-A19.A18 Tuberculosis of other organs
Contraindications:Hypersensitivity (incl. To cycloserine); organic diseases of the central nervous system (including cerebrosclerosis); atherosclerosis of the brain: epilepsy; mental disorders; alcoholism; pregnancy; lactation period; children's age till 14 years.
Carefully:Elderly age; ischemic heart disease, chronic heart failure; chronic renal failure, violations of the liver, peptic ulcer of the stomach and duodenum.
Pregnancy and lactation:Application in pregnancy and breast-feeding is contraindicated. The concentration of terizidone in breast milk is close to that in blood plasma. In case of need, it is necessary to stop breastfeeding.
Action category for the fetus by FDA - FROM
Dosing and Administration:Inside, regardless of food intake (the dose is indicated by terizidon): adults and children over 14 years of age and body weight less than 60 kg - 300 mg 2 times / day (600 mg / day); with a body weight of 60-80 kg - 300 mg 3 times / day (900 mg / day). Adults with a body weight of more than 80 kg - 600 mg 2 times / day (1200 mg / day).
At CC less than 30 ml / min dose and frequency of intake is reduced (250 mg 1 time / day daily or 500 mg 3 times / week).At a creatinine concentration of more than 2 mg / dl, it is contraindicated. Duration of treatment - 3-4 months.
Under no circumstances should prematurely stop or temporarily interrupt the treatment course started with a combination of terizidone and pyridoxine or take it irregularly.
Side effects:From the nervous system: headache, dizziness, increased excitability, tremor, insomnia, a feeling of intoxication; in isolated cases - epileptiform convulsions, depression, psychosis.
From the digestive system: rarely - abdominal pain, flatulence, diarrhea.
Other: very rarely - allergic reactions, skin rash.
Additionally (due to the presence of pyridoxine): hypersecretion of HCl, numbness and the appearance of a feeling of compression in the extremities (a symptom of "stocking" and "gloves"), a decrease in lactation.
Overdose:Symptoms: increased neurotoxicity, incl. epileptiform seizures, a violation of the function of the gastrointestinal tract.
Treatment: symptomatic, the appointment of activated charcoal, anticonvulsant drugs. For the prevention of neurotoxic effects - the appointment of anticonvulsant and sedative drugs. Hemodialysis is effective.
Interaction:Terizidone
Ethanol increases the risk of epileptic seizures.
Ethionamide increases the risk of side effects from the central nervous system (especially seizures).
Isoniazid increases the incidence of dizziness, drowsiness.
Pyridoxine
Strengthens the action of diuretics; weaken the pharmacological effects of levodopa. Isoniazid, penicillamine, cycloserine and estrogen-containing oral contraceptives weaken the effect of pyridoxine.
Special instructions:Terizidone can cause a deficiency of cyanocobolamine (B12) and / or folic acid, in this case it is necessary to conduct an appropriate examination and treatment of the patient, increase the dose of vitamin B12 and / or folic acid.
It should be monitored monthly blood and urine indicators, liver function (ALT, ACT, bilirubin). It is necessary to avoid the use of ethanol, t. its simultaneous administration with terizidone increases the frequency of side effects (up to the development of seizures).
The use of cycloserine at the same time is prohibited due to a possible overdose.
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.With severe liver damage pyridoxine in large doses can cause a deterioration in its function. When determining urobilinogen using Ehrlich's reagent pyridoxine can distort results.
During the period of treatment, it is necessary to refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.