Thiotriazolin®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT THIOTRIAZOLINE® (THIOTRIAZOLIN)

Composition:

Active substance: 1 ml of solution contains 25 mg of morpholine salt of thiatic acid, calculated as 100% substance, equivalent to 16.6 mg of thiatic acid

Excipients: water for injections.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: transparent colorless or slightly yellowish liquid.

Pharmacotherapeutic group.

Cardiological agents. Other cardiological agents. Thiatic acid.

ATC code C01EB23.

Pharmacological Properties.

Pharmacodynamics.

The pharmacological effect of thiotazic acid is due to its anti-ischemic, membrane-stabilizing, antioxidant, and immunomodulatory actions.

The drug's effect is achieved by enhancing compensatory activation of anaerobic glycolysis and stimulating oxidation processes in the Krebs cycle, thereby preserving intracellular ATP stores. The presence of a thiol sulfur with redox properties and a tertiary nitrogen that binds excess hydrogen ions within the molecular structure of thiotazic acid promotes activation of the antioxidant system. The strong reducing properties of the thiol group lead to reactions with reactive oxygen species and lipid radicals. Reactivation of anti-radical enzymes—superoxide dismutase, catalase, and glutathione peroxidase—prevents the initiation of reactive oxygen species.

The action of thiotazic acid results in inhibition of lipid peroxidation in ischemic areas of the myocardium, reduced myocardial sensitivity to catecholamines, prevention of progressive depression of cardiac contractile function, and stabilization and reduction of myocardial necrosis and ischemia zones. Improvement of blood rheological properties occurs via activation of the fibrinolytic system. Enhanced myocardial metabolism, increased myocardial contractility, and support of cardiac rhythm normalization make thiotazic acid suitable for treatment of patients with various forms of ischemic heart disease.

In addition to its use in cardiology, thiotazic acid is also applied in the treatment of liver and other internal organ diseases due to its pronounced hepatoprotective properties. The drug prevents hepatocyte destruction, reduces fatty infiltration and the spread of centrilobular liver necroses, supports reparative regeneration of hepatocytes, and normalizes protein, carbohydrate, lipid, and pigment metabolism within them. It increases the rate of bile synthesis and excretion and normalizes its chemical composition.

Pharmacokinetics.

Maximum plasma concentration of thiotazic acid is achieved within 0.84 hours after intramuscular administration and within 0.1 hours after intravenous administration. Plasma protein binding does not exceed 10%. Thiotazic acid predominantly accumulates in the kidneys (31%). It also accumulates significantly in the colon, heart, and spleen, and to the least extent—in the small intestine and lungs (1–2%).

Clinical characteristics.

Indications.

In complex treatment of ischemic heart disease: angina pectoris, myocardial infarction, postinfarction cardiosclerosis; as an additional agent in the therapy of cardiac arrhythmias.

In complex treatment of chronic hepatitis, alcoholic hepatitis, fibrosis and liver cirrhosis.

Contraindications.

Hypersensitivity to thiotropic acid, acute renal failure.

Interaction with other medicinal products and other types of interactions. Thiotriazolin® as a cardioprotective agent can be used in combination with basic therapies for ischemic heart disease. As a hepatoprotective agent, it can be combined with conventional treatment methods for hepatitis of corresponding etiology.

Special precautions.

None.

Use during pregnancy or breastfeeding. There is insufficient experience with the use of the drug during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery. Caution should be exercised when driving or operating other machinery in case of adverse reactions affecting the central or peripheral nervous system.

Method of administration and dosage.

For myocardial infarction and unstable angina, administer Thiotriazolin® intravenously slowly at a rate of 2 ml/min, 4 ml of 25 mg/ml solution (100 mg); or intravenously by infusion at a rate of 20–30 drops per minute (4 ml of 25 mg/ml solution diluted in 150–250 ml of 0.9% sodium chloride solution); or intramuscularly, 4 ml of 25 mg/ml solution (100 mg) 2–3 times daily. Treatment course – 14 days.

For exertional angina, administer Thiotriazolin® intramuscularly, 4 ml of 25 mg/ml solution twice daily (daily dose – 200 mg). Treatment course – 14 days.

For angina at rest and postinfarction cardiosclerosis, administer Thiotriazolin® intramuscularly, 2 ml of 25 mg/ml solution 3 times daily. Treatment course – 20–30 days.

For chronic hepatitis with pronounced disease activity, during the first 5 days administer Thiotriazolin® intramuscularly, 2 ml of 25 mg/ml solution (50 mg) 2–3 times daily; or intravenously slowly at a rate of 2 ml/min, 4 ml of 25 mg/ml solution (100 mg) once daily; or by infusion at a rate of 20–30 drops per minute (2 ampoules of 25 mg/ml solution diluted in 150–250 ml of 0.9% sodium chloride solution). From day 5 to day 20 of therapy, administer Thiotriazolin® tablets (100 mg three times daily).

For chronic hepatitis with minimal or moderate disease activity, administer Thiotriazolin® intramuscularly, 2 ml of 25 mg/ml solution 3 times daily. Treatment course – 20–30 days.

For liver cirrhosis, treatment course is 60 days. Begin treatment with intramuscular administration of 2 ml of 25 mg/ml solution (50 mg) 3 times daily for 5 days, followed by continuation with tablets (100 mg three times daily).

Children.

Experience with the use of the drug in children is insufficient.

Overdose. In case of overdose, concentration of sodium and potassium in urine increases. In such cases, the drug should be discontinued. Treatment is symptomatic.

Adverse reactions.

The drug is generally well tolerated. In patients with increased individual sensitivity, the following may occur:

Skin and subcutaneous tissue disorders: itching, skin hyperemia, rash, cases of urticaria;

Immune system disorders: cases of angioneurotic edema, anaphylactic shock described in the background of taking other drugs;

Other: fever, chills, and injection site reactions.

In patients, predominantly elderly, receiving other medications, the following may occur:

Central and peripheral nervous system disorders: general weakness, dizziness, tinnitus, headache;

Cardiovascular system disorders: tachycardia, arterial hypertension, cases of decreased blood pressure;

Gastrointestinal disorders: dyspeptic symptoms, including dry mouth, nausea, bloating, vomiting;

Respiratory system disorders: dyspnea, wheezing.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 2 ml in an ampoule, 10 ampoules in a blister pack, 1 blister pack in a carton. 4 ml in an ampoule, 5 ampoules in a blister pack, 2 blister packs in a carton.

Prescription category. By prescription only.

Manufacturer. JSC "Halychpharm". Developed by NPO "Pharmatron" and DNCLZ, Kharkiv.

Manufacturer's address and place of business.

6/8 Opryshkovska Street, Lviv, 79024, Ukraine.