Tiocetam® forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TIOCETAMâ FORTE (THIOCETAM FORTE)

Composition:

Active substances: 1 tablet contains: piracetam calculated as 100 % substance – 400 mg; morpholine salt of thiotropic acid calculated as 100 % substance, equivalent to 66.5 mg of thiotropic acid – 100 mg;

Excipients: potato starch; mannitol; powdered sugar; magnesium stearate; povidone; coating mixture **.

** - coating mixture contains: hypromellose; lactose monohydrate; titanium dioxide (E 171); polyethylene glycol/macrogol; triacetin.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets of white or almost white color, oval-shaped, with a score line on one side of the tablet.

Pharmacotherapeutic group. Psychostimulants and nootropics.

ATC code N06B X.

Pharmacological Properties

Pharmacodynamics

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

The drug improves integrative and cognitive brain functions, enhances learning efficiency, helps eliminate symptoms of amnesia, and improves indices of short-term and long-term memory.

The pharmacological effect of the drug is due to the mutually potentiating actions of thiatic acid and piracetam.

The drug is capable of accelerating glucose oxidation in both aerobic and anaerobic oxidation reactions, normalizing bioenergetic processes, increasing ATP levels, and stabilizing brain tissue metabolism.

The drug inhibits pathways of reactive oxygen species formation, reactivates the antioxidant enzyme 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 the areas of necrosis and ischemia.

Pharmacokinetics

The drug is well absorbed after oral administration and penetrates various organs and tissues, including brain tissue. It crosses the placental barrier. Each component of the drug is metabolized separately. Piracetam is practically not metabolized in the body and is excreted in the urine. Elimination half-life is 4–8 hours. The morpholine salt of thiatic acid is rapidly absorbed after oral intake, with absolute bioavailability of 53%. Maximum plasma concentration is reached within 1.6 hours after a single 200 mg dose. The elimination half-life is approximately 8 hours.

Clinical characteristics.

Indications.

Transient and chronic cerebral circulation disorders caused by atherosclerosis of cerebral vessels and previous cerebral circulation disorders. The drug is also indicated in cerebral circulation disorders, cerebral metabolic disturbances caused by traumatic brain injuries, intoxications, diabetic encephalopathy, as well as in the rehabilitation period after ischemic stroke.

Contraindications.

Hypersensitivity to piracetam or pyrrolidone derivatives, and/or thiatic acid, as well as to any other component of the drug.

Acute cerebral circulation disorder of hemorrhagic type.

Acute renal failure. Terminal stage of renal failure.

Huntington's chorea.

Interaction with other medicinal products and other types of interactions.

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

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

Thyroid hormones.

When used concomitantly with thyroid hormones (T3+T4), increased irritability, disorientation, and sleep disturbances may occur.

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 ratio (INR) of 2.5–3.5. However, when used concomitantly, a significant reduction in platelet aggregation, fibrinogen levels, von Willebrand factors (VIII:C; VIII:vW:Ag; VIII:vW:Rco), and blood and plasma viscosity was observed.

Pharmacokinetic interactions.

The likelihood of changes in piracetam's pharmacodynamics due to other medicinal products is low, since 90% of the drug is excreted unchanged in urine.

In vitro, piracetam does not inhibit cytochrome P450 isoenzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A9/11 at concentrations of 142, 426, and 1422 µg/mL.

At a concentration of 1422 µg/mL, slight inhibition of CYP2A6 (21%) and 3A4/5 (11%) was observed. However, the Ki values for these two CYP isoenzymes are sufficiently high to exceed 1422 µg/mL. Therefore, metabolic interactions with drugs undergoing biotransformation by these enzymes are unlikely.

Antiepileptic medicinal products.

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

Concomitant use with enalapril or captopril increases the risk of adverse cardiovascular reactions.

Alcohol.

Concomitant intake with alcohol did not affect the serum concentration of piracetam, and serum alcohol concentration was not altered when 1.6 g of piracetam was administered.

Special precautions.

The drug should be used with caution in elderly patients suffering from cardiovascular disorders, as adverse reactions occur more frequently in this patient group.

Allergic reactions are more common in individuals with a predisposition to allergies.

Effect on platelet aggregation.

Since piracetam reduces platelet aggregation, the drug should be administered with caution in patients with coagulation disorders, conditions that may be associated with bleeding (e.g., gastrointestinal ulcer), during major surgical procedures (including dental interventions), in patients with signs of severe hemorrhage, or in those with a history of hemorrhagic stroke; also in patients receiving anticoagulants, platelet antiaggregants, including low-dose acetylsalicylic acid. The drug is excreted by the kidneys; therefore, special attention should be paid to patients with renal impairment.

Elderly patients.

During long-term therapy in elderly patients, regular monitoring of renal function parameters is recommended. Dose adjustment may be necessary based on creatinine clearance test results.

The drug contains lactose as an excipient, which should be taken into account in patients with galactose intolerance, lactase deficiency, or glucose/galactose malabsorption.

One tablet of Tiocetam® Forte contains 0.007 g of powdered sugar, which should be considered in patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

Should not be used.

Ability to affect reaction rate when driving or operating machinery.

The use of the drug is not recommended when driving vehicles or operating machinery requiring high attention due to the risk of possible adverse reactions from the nervous system.

Method of Administration and Dosage

The dosage and duration of treatment are determined by a physician individually for each case, depending on the nature and course of the disease.

For transient and chronic cerebral circulation disorders, and during the rehabilitation period after ischemic stroke: 1 tablet 3 times a day for 25–30 days.

Tioceptam® Forte tablets should be taken 30 minutes before meals.

The treatment course lasts from 2–3 weeks to 3–4 months.

For the treatment of diabetic encephalopathy: 1 tablet 3 times a day for 45 days.

Children. Not to be used.

Overdose

Overdose is not possible when therapeutic doses are used.

If the prescribed doses are exceeded, adverse effects of the drug may occur or intensify (e.g., excitement, sleep disturbances, dyspeptic symptoms). In such cases, the dose should be reduced and symptomatic treatment administered (induced vomiting, gastric lavage).

In cases of overdose, increased concentrations of sodium and potassium in urine may occur. In such cases, the drug should be discontinued.

Adverse reactions.

During clinical use of the drug Tiocetam® Forte, adverse reactions may occur:

Central and peripheral nervous system: headache, general weakness, insomnia, drowsiness, anxiety, inner tension;

Gastrointestinal tract: nausea, vomiting, dry mouth, diarrhea;

Immune system, skin and subcutaneous tissue: allergic reactions including rash, itching, urticaria, sweating;

Vestibular system: dizziness.

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

• Piracetam:

Blood and lymphatic system: hemorrhagic disorders;

Immune system: hypersensitivity, anaphylactoid reactions;

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

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

Ear and labyrinth disorders: dizziness;

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

Skin and subcutaneous tissue: angioedema, dermatitis, rash, urticaria, itching;

Reproductive system and breastfeeding: increased sexual activity;

General disorders: asthenia, weight gain.

• Thiotropic acid:

Skin and subcutaneous tissue: itching, skin hyperemia, rash, urticaria, angioedema;

Immune system: anaphylactic shock;

Central and peripheral nervous system: dizziness, tinnitus;

Cardiovascular system: tachycardia, increased blood pressure;

Gastrointestinal tract: dyspepsia, including dry mouth, bloating, nausea, vomiting;

Respiratory system: dyspnea, wheezing;

General disorders: fever, general weakness.

Shelf life. 3 years.

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

Packaging. 10 tablets per blister pack, 3 or 6 blister packs per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business.

139 Saksaganskogo Street, Kyiv, 01032, Ukraine.