Terizidone

Terizidone is an anti-tuberculosis drug.

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

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

Indications Terizidone

It is used for tuberculosis (pulmonary or extrapulmonary), and also 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 bring results).

Release form

The drug is released in capsules - 10 pieces inside a blister pack; there is 1 such pack in a box.

Pharmacodynamics

The following strains show sensitivity to terizidone: Koch's bacillus, hay bacillus, Candida albicans, Escherichia coli, epidermal staphylococci with Klebsiella pneumoniae, Staphylococcus aureus and Pasteurella multocida with Shigella, as well as Pseudomonas aeruginosa, Salmonella enterica, individual streptococcal strains, including pyogenic ones, and Rickettsia, leading to the development of paratyphoid, typhus and endemic typhus. [ 3 ]

Pharmacokinetics

Suction.

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

Distribution processes.

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

Metabolic processes and excretion.

Excretion through the urinary tract is gradual and low-speed, so that even after 24 hours from the moment of oral administration, plasma levels remain at the mid-Cmax level. Prolonged excretion through the urinary tract maintains therapeutically effective urinary levels for 12 hours.

60-70% (in an unchanged state) is excreted in 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. No more than 15-20 mg/kg of the drug is allowed per day.

People over 60 years of age and weighing less than 60 kg should take 0.25 g of the medication twice a day.

• Application for children

There is no information regarding the therapeutic efficacy or safety of 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 in case of use during pregnancy, as well as its impact on reproductive activity. Terizidone is used in pregnant women only in situations where the probable benefit to the woman is more expected than the possibility of developing negative consequences for the fetus. Therapy in this case is carried out only under medical supervision.

The drug levels in breast milk are close to its plasma values, so breastfeeding should be discontinued during treatment.

Contraindications

Main contraindications:

• severe intolerance to terizidone or other components of the medication;
• epilepsy;
• severe renal failure;
• alcoholism;
• psychoses.

Side effects Terizidone

Side effects include:

• manifestations of intolerance may occur, including itching and epidermal rash;
• lesions affecting the function of the nervous system: insomnia, tremor, convulsions, dizziness, drowsiness, dysarthria and headaches, as well as hyperreflexia, peripheral paresis, comatose state, as well as clonic seizures (minor or major);
• mental disorders: mania, confusion, with memory loss, mood lability, psychosis (sometimes with suicidal attempts), aggressiveness, changes in behavior, severe irritability and depression;
• problems with the functioning of the lymph and blood system: anemia (also sideroblastic or megaloblastic forms);
• disorders affecting the hepatobiliary system: increased intrahepatic aminotransferase levels, as well as liver dysfunction;
• digestive disorders: heartburn, nausea and diarrhea, especially in people with liver pathologies.

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

Overdose

Acute intoxication may develop when using more than 1000 mg of the drug. Chronic poisoning occurs depending on the dosage, usually developing with daily use of more than 0.5 g of the drug.

Often, symptoms of poisoning are associated with the work of the central nervous system: increased irritability, headaches, psychosis, confusion, dizziness, dysarthria and paresthesia. When large doses are administered, convulsions, peripheral paresis and a comatose state may be observed, or manifestations of other negative signs may be potentiated. Ethyl alcohol increases the likelihood of epileptic seizures.

Symptomatic and supportive measures are required; activated carbon will be more effective in reducing drug absorption than gastric lavage. If neurotoxic signs appear, 0.2-0.3 g of pyridoxine should be administered daily. Terizidone is excreted from the blood by hemodialysis, but the possibility of toxic effects cannot be ruled out, which can be life-threatening.

Interactions with other drugs

Administration with ethionamide enhances the neurotoxic activity of terizidone.

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

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

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

Combination with phenytoin may lead to an increase in its blood levels.

Storage conditions

Terizidone should be stored in a place closed to small children. Temperature values are maximum 25ºС.

Shelf life

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

Analogues

Analogues of the drug are Resonizat and Loxidon with Tisidone.