Terizidone

Terizidone is an anti-tuberculosis drug.

The drug completely blocks the activity of the enzyme that transforms alanine into the alanyl-alanine 2-peptide element, which is the main component of the bacterial membrane of mycobacteria. Does not have cross-resistance with respect to other anti-tuberculosis drugs. [1]

The drug has an extensive and pronounced antimicrobial effect; it has a significant effect not only on strains that provoke the development of tuberculosis or infections of the urinary system, but also on strains resistant to other known antibiotics. The MIC values of terizidone for susceptible strains are 4-130 mg / ml. [2]

Indications Terizidone

It is used for tuberculosis (pulmonary or extrapulmonary), and in addition, for tuberculosis affecting the urogenital system and kidneys (when tuberculosis mycobacteria demonstrate resistance to the main anti-tuberculosis substances, or other anti-tuberculosis treatment does not work).

Release form

The production of drugs is realized in capsules - 10 pieces inside a contour package; in a box - 1 such package.

Pharmacodynamics

Sensitivity to terizidone is shown by such strains: Koch's bacillus, hay bacillus, Candida albicans, Escherichia coli, Staphylococcus epidermidis with Klebsiella pneumoniae, Staphylococcus aureus and Pasteurella multicide with Shigella, and among this Pseudomonas aeruginosa, encaalmonella and rickettsia, leading to the development of paratyphoid fever, typhus and endemic typhus. [3]

Pharmacokinetics

Suction.

When administered orally, terizidone is fully (70-90%) and is absorbed at high speed when administered on an empty stomach. Cmax values reach after 2-4 hours.

Distribution processes.

The drug is distributed in many fluids and tissues - bile, lungs, pleural fluid, semen, synovium, cerebrospinal fluid, lymph and ascitic fluid. The substance penetrates into the cerebrospinal fluid by 80-100% of the plasma values. The highest rates are observed in the case of the development of inflammation affecting the meningeal membranes.

Metabolic processes and excretion.

Excretion through the urinary ducts is carried out in stages, at a low speed, therefore, even after 24 hours from the moment of oral administration, plasma parameters remain at the middle level of Cmax. Prolonged excretion through the urethra induces maintenance of therapeutically effective urinary values for 12 hours.

60-70% (unchanged) is excreted in the urine through glomerular filtration. A small part is excreted in feces, and some more is involved in metabolic processes.

Dosing and administration

The drug should be used in a dosage of 0.25 g (1 capsule), 3 times a day. It is allowed to consume no more than 15-20 mg / kg of the drug per day.

Persons over the age of 60 with a weight below 60 kg need to take 0.25 g of the medication 2 times per day.

• Application for children

There is no information regarding the therapeutic efficacy, as well as the safety of using the drug in pediatrics, which is why it is not prescribed to children.

Use Terizidone during pregnancy

There is no information regarding the possibility of developing a negative effect of terizidone on the fetus if used during pregnancy, as well as its effects on reproductive activity. Terizidone is used in pregnant women only in situations where the likely benefit for the woman is more expected than the possibility of negative consequences for the fetus. In this case, therapy is carried out only under medical supervision.

The drug values inside breast milk are close to its plasma values, therefore, breastfeeding should be abandoned for the period of treatment.

Contraindications

The main contraindications:

• severe intolerance to terizidone or other elements of the medication;
• epilepsy;
• failure of the kidneys in a severe degree;
• alcoholism;
• psychosis.

Side effects Terizidone

Among the side signs:

• manifestations of intolerance may occur, including itching and epidermal rash;
• lesions affecting the function of the NS: insomnia, tremor, convulsions, dizziness, drowsiness, dysarthria and headaches, and in addition to this hyperreflexia, peripheral paresis, coma, as well as seizures of a clonic nature (small or large);
• mental disorders: mania, confusion, in which there is loss of memory, mood lability, psychosis (sometimes with suicidal attempts), aggressiveness, changes in behavior, severe irritability and depression;
• problems with the work of the lymph and blood system: anemia (also sideroblastic or megaloblastic forms);
• disorders affecting the hepatobiliary system: an increase in indicators of intrahepatic aminotransferases, as well as a disorder of hepatic activity;
• disorders of the digestive function: heartburn, nausea and diarrhea, especially in people with hepatic pathologies.

The development of HF in the active phase or exacerbation of CHF was noted in people who consumed 1000-1500 mg of terizidone per day.

Overdose

With the use of more than 1000 mg of the drug, acute intoxication may develop. Chronic poisoning appears taking into account the dosage, usually developing with daily use of more than 0.5 g of drugs.

Often the symptoms of poisoning are associated with the work of the central nervous system: increased irritability, headaches, psychosis, confusion, dizziness, dysarthria and paresthesia. With the introduction of large portions, convulsions, peripheral paresis and a coma may be noted, or manifestations of other negative signs may be potentiated. Ethyl alcohol increases the likelihood of epileptic seizures.

Symptomatic and supportive actions are required; the use of activated carbon will be more effective for weakening drug absorption than gastric lavage. When neurotoxic signs appear, 0.2-0.3 g of pyridoxine should be administered per day. Terizidone is excreted from the blood during hemodialysis, but the likelihood of a toxic effect, which can be life-threatening, cannot be ruled out.

Interactions with other drugs

Administration with ethionamide enhances the neurotoxic activity of terizidone.

It is forbidden to combine the medicine with alcoholic beverages, especially in the case of using large portions of drugs (alcohol increases the risk of developing epileptic seizures).

Pyridoxine weakens the toxic effect of the drug on the central nervous system.

People who use the medication together with isoniazid should be monitored by a doctor, because such a combination can potentiate the toxic effect on the central nervous system, which may require a change in dosage.

The combination with phenytoin can lead to an increase in its blood count.

Storage conditions

Therizidone must be kept out of the reach of small children. Temperature values - maximum 25 ° C.

Shelf life

Terizidone can be used for a 2-year term from the date of marketing of the therapeutic substance.

Analogs

Analogues of drugs are the drugs Resonizat and Loxidon with Tizidone.