Thiocetam®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT THIOCETAM® (THIOSETAM)

Composition:

Active substances: 1 ml of solution contains morpholinium salt of thiotropic acid, recalculated to 100 % substance – 25 mg, equivalent to 16.6 mg of thiotropic acid; piracetam – 100 mg;

Excipient: water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear colorless or slightly yellowish liquid.

Pharmacotherapeutic group. Other psychostimulants and nootropic agents.

ATC code N06BX.

Pharmacological Properties.

Pharmacodynamics.

Tiocetam® belongs to the group of cerebroactive agents and has nootropic, anti-ischemic, antioxidant, and membrane-stabilizing properties.

The pharmacological effect of the drug is due to the mutually potentiating action of thiotropic acid and piracetam.

Tiocetam® accelerates glucose utilization in aerobic and anaerobic oxidation reactions, normalizes bioenergetic processes, stabilizes brain tissue metabolism, and increases the body's resistance to hypoxia.

The drug inhibits pathways of reactive oxygen species formation, reactivates the enzymatic antioxidant system—particularly superoxide dismutase—suppresses free radical processes in brain tissue during ischemia, improves blood rheological properties by activating the fibrinolytic system, and stabilizes as well as reduces areas of necrosis and ischemia.

Tiocetam® enhances the activity of the metabolic GABA shunt and increases GABA concentration in ischemic tissues.

Tiocetam® improves integrative and cognitive brain functions, facilitates the learning process, eliminates amnesia, and enhances indices of short-term and long-term memory. Tiocetam® alleviates the consequences of stress (feelings of anxiety, phobias, depression, sleep disturbances) and reduces delays in physical and mental development in premature infants.

Pharmacokinetics.

Not studied.

Clinical characteristics.

Indications. Treatment of ischemic stroke and its consequences, such as speech disorders, psychic and somatic disturbances, reduced activity, emotional disturbances; treatment (in the recovery period) of vascular, toxic and traumatic encephalopathy; alleviation of alcohol withdrawal syndrome in alcohol intoxication, diabetic encephalopathy.

Contraindications.

• Hypersensitivity to piracetam or thiocetamic acid;
• terminal stage of renal failure;
• Huntington's chorea;
• acute cerebral circulation disorder of hemorrhagic type.

Interaction with other medicinal products and other types of interactions.

Tiotsetam® must not be administered with drugs having an acidic pH.

Due to the presence of piracetam in the formulation, the following types of interactions are possible:

Thyroid hormones. Combination with thyroid hormones may lead to increased irritability, disorientation, and sleep disturbances.

Acenocoumarol. In patients with severe recurrent thrombosis, administration of high-dose piracetam (9.6 g/day) did not affect the dosage of acenocoumarol required to achieve a prothrombin time of 2.5–3.5. However, when used concomitantly, a significant reduction was observed in platelet aggregation, fibrinogen levels, von Willebrand factor levels (coagulation activity (VIII:C); ristocetin cofactor (VIII:vW:Rco) and protein in blood plasma (VIII:vW:Ag)), as well as in blood and plasma viscosity.

Pharmacokinetic interactions. The potential for changes in piracetam's pharmacodynamics under the influence of other drugs is low, since 90% of the drug is excreted unchanged in urine.

In vitro studies show that piracetam does not inhibit cytochrome P450 isoenzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A9/11 at concentrations of 142, 426, and 1422 mcg/mL. At a concentration of 1422 mcg/mL, slight inhibition of CYP2A6 (21%) and CYP3A4/5 (11%) was observed. However, the Ki values for these two CYP isoenzymes are sufficiently high to exceed 1422 mcg/mL. Therefore, metabolic interaction with drugs undergoing biotransformation by these enzymes is unlikely.

Antiepileptic agents. Administration of piracetam at a dose of 20 mg/day for 4 weeks or longer did not alter the concentration-time curve or maximum serum concentration of antiepileptic drugs (carbamazepine, phenytoin, phenobarbital, sodium valproate) in patients with epilepsy.

Alcohol. Concurrent intake with alcohol did not affect serum piracetam concentrations, and serum alcohol concentration was not altered following administration of 1.6 g of piracetam.

Special precautions for use.

The drug should be prescribed with caution to patients with chronic renal insufficiency.

Caution should be exercised when prescribing the drug to elderly patients with cardiovascular diseases, since the adverse reactions mentioned above occur more frequently in this patient group.

Allergic reactions occur more frequently in individuals predisposed to allergies.

Since piracetam reduces platelet aggregation, the drug should be administered with caution to patients with coagulation disorders, conditions that may be associated with bleeding (gastrointestinal ulcers), during major surgical procedures (including dental interventions), in patients with symptoms of severe bleeding or a history of hemorrhagic stroke, and in patients receiving anticoagulants or platelet antiaggregants, including low-dose acetylsalicylic acid.

During long-term therapy in elderly patients, regular monitoring of renal function parameters is recommended.

Use during pregnancy or breastfeeding.

Should not be used.

Ability to influence reaction rate while driving or operating machinery.

Currently, there are no such reports. However, caution should be exercised when administering Tiocetam® to individuals who drive vehicles or operate hazardous machinery, considering possible adverse reactions affecting the nervous system.

Dosage and Administration.

For ischemic stroke and treatment of its consequences, administer 20–30 mL of the drug, previously diluted in 100–150 mL of 0.9% sodium chloride solution, once daily by intravenous infusion. The treatment course lasts for 2 weeks.

For the treatment of encephalopathy and management of alcohol withdrawal syndrome during alcohol intoxication, administer 5 mL of the drug intramuscularly once daily for 10–15 days.

In diabetic encephalopathy, administer 5 mL intramuscularly once daily for 10 days, followed by 1 tablet of Tiocetam® Forte or 2 tablets of Tiocetam® three times daily for 45 days, taken 30 minutes before meals.

Children. Not used.

Overdose.

Symptoms: intensification of the drug's adverse effects.

In such cases, discontinue the drug and administer symptomatic treatment.

Adverse Reactions

When using the drug Thiocetam®, injection solution, the following adverse reactions may occur:

Central and peripheral nervous system: headache, general weakness;

Gastrointestinal tract: nausea, vomiting;

Immune system: allergic reactions, including rash, pruritus, urticaria, angioedema, anaphylactic shock;

Cardiovascular system: decreased arterial pressure;

Vestibular system: dizziness;

General disorders and administration site conditions: skin hyperemia and itching at the injection site.

Adverse reactions associated with individual components of the drug may occur in patients:

• Pyritinol:

Blood and lymphatic system: hemorrhagic disorders;

Immune system: hypersensitivity, anaphylactoid reactions;

Psychiatric disorders: irritability, depression, increased excitability, anxiety, confusion, hallucinations;

Nervous system: hyperkinesia, somnolence, ataxia, loss of balance, increased frequency of epileptic seizures, headache, insomnia, tremor;

Ear and labyrinth disorders: vertigo;

Gastrointestinal system: abdominal pain, upper abdominal pain, diarrhea, nausea, vomiting;

Skin and subcutaneous tissue disorders: angioedema, dermatitis, rash, urticaria, pruritus;

Reproductive system and breastfeeding: increased sexual activity;

Vascular disorders: hypotension, thrombophlebitis;

General disorders and administration site reactions: asthenia, injection site pain, chills, weight gain.

• Thiotropic acid:

In patients, mainly elderly, particularly when taking other medications, the following have been reported:

Allergic reactions: skin hyperemia, fever;

Central and peripheral nervous system: dizziness, tinnitus;

Cardiovascular system: tachycardia, increased arterial pressure;

Gastrointestinal tract: dry mouth, bloating;

Respiratory system: dyspnea, asthma attacks.

Shelf life. 5 years.

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

Incompatibility. Not established.

Packaging. 5 ml in an ampoule, 5 ampoules in a blister pack covered with film, 2 blister packs per carton.

10 ml in an ampoule, 5 ampoules in a blister pack covered with film, 2 blister packs per carton.

10 ml in an ampoule, 10 ampoules in a box.

Prescription status. Prescription only.

Manufacturer: JSC "Halychpharm".

Manufacturer's address and location of business activity:
6/8 Opryshkivska Street, Lviv, 79024, Ukraine.