Thioktodar

INSTRUCTIONS for medical use of the medicinal product THIOCTODAR (THIOCTODAR)

Composition:

Active substance: 1 ml of solution contains 30 mg of thioctic (α-lipoic) acid;

Excipients: tromethamine, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear liquid, yellow to yellowish-green in color.

Pharmacotherapeutic group.

Agents affecting the digestive system and metabolic processes.

ATC code A16AX01.

Pharmacological Properties.

Pharmacodynamics.

Thioctic acid is a vitamin-like substance produced in the body that functions as a coenzyme in the oxidative decarboxylation of α-keto acids. Hyperglycemia caused by diabetes mellitus leads to glucose deposition on vascular matrix proteins and the formation of advanced glycation end-products (AGEs). This process results in reduced endoneurial blood flow and endoneurial hypoxia/ischemia associated with increased production of reactive oxygen species, which damage nerves, as well as depletion of the antioxidant glutathione in peripheral nerves. In studies on rats, thioctic acid influenced the biochemical processes induced by streptozotocin-induced diabetes, reducing the formation of advanced glycation end-products, improving endoneurial blood flow, and increasing physiological glutathione levels, thereby acting as an antioxidant against free radicals in nerves affected by diabetic processes. These experimentally observed effects suggest that thioctic acid may improve peripheral nerve function. This particularly applies to sensory disturbances occurring in polyneuropathy, which may manifest as dysesthesias and paresthesias, such as burning sensations, pain, numbness, or "pins and needles." Clinical studies investigating the efficacy of thioctic acid in symptomatic treatment of diabetic polyneuropathy have confirmed beneficial effects of thioctic acid on these symptoms, including paresthesias, burning sensations, numbness, and pain.

Pharmacokinetics.

Thioctic acid undergoes extensive first-pass hepatic metabolism. There are significant individual variations in systemic bioavailability. Thioctic acid is biotransformed via side-chain oxidation and conjugation, with 80–90% of its metabolites excreted by the kidneys. The elimination half-life of thioctic acid is 25 minutes, and total plasma clearance is 10–15 ml/min/kg. After a 30-minute infusion of 600 mg of thioctic acid, its plasma concentration reaches approximately 20 µg/ml. Only a negligible amount of unchanged substance is excreted in urine.

Clinical characteristics.

Indications.

Paresthesia in diabetic polyneuropathy.

Contraindications.

Hypersensitivity to thioctic acid or to any of the excipients.

Cardiac and respiratory failure, acute phase of myocardial infarction, acute cerebrovascular events, dehydration, chronic alcoholism, and other conditions that may lead to lactic acidosis.

Interaction with other medicinal products and other forms of interaction.

Thioctic acid reacts with ionic metal complexes (e.g., cisplatin); therefore, the medicinal product may reduce the efficacy of cisplatin.

Thioctic acid forms poorly soluble complex compounds with sugar molecules (e.g., levulose solution).

Since thioctic acid is a metal chelator, it should not be administered concomitantly with metals (iron, magnesium-containing preparations).

Thioctic acid may enhance the hypoglycemic effect of insulin and/or other antidiabetic agents; therefore, regular monitoring of blood glucose levels is recommended, especially at the beginning of thioctic acid therapy. In some cases, to prevent symptoms of hypoglycemia, it may be necessary to reduce the dose of insulin and/or oral antidiabetic agent.

Ethanol reduces the therapeutic efficacy of thioctic acid.

Special precautions for use.

When administering Thioctodar parenterally, there is a risk of allergic reactions, including anaphylactic shock; therefore, patients should be monitored for such reactions. If symptoms such as itching, nausea, or malaise occur, administration of the drug must be stopped immediately and appropriate therapeutic measures initiated.

In isolated cases, severe anaphylactic reactions associated with the use of the drug may develop in patients with decompensated or inadequately controlled diabetes and worsening general health.

Cases of autoimmune insulin syndrome (AIS) have been reported during treatment with thioctic acid. Patients with human leukocyte antigen genotype (alleles HLA-DRB1*04:06 and HLA-DRB1*04:03) are more susceptible to developing AIS during thioctic acid therapy. The HLA-DRB1*04:03 allele (susceptibility coefficient for AIS development – 1.6) is particularly prevalent among Caucasian populations (more common in Southern Europe than in Northern Europe), while the HLA-DRB1*04:06 allele (susceptibility coefficient for AIS development – 56.6) is especially common in Japanese and Korean patients.

AIS should be considered in the differential diagnosis of spontaneous hypoglycemia in patients receiving thioctic acid.

Frequent monitoring of blood glucose is necessary when treating patients with diabetes mellitus. In some cases, dosage adjustment of antidiabetic agents may be required to prevent hypoglycemia.

During treatment of polyneuropathy, transient increased sensitivity due to regenerative processes may occur, accompanied by paresthesia with a "pins and needles" sensation.

Chronic alcohol consumption is a risk factor for polyneuropathy and may reduce the efficacy of Thioctodar. Therefore, alcohol consumption should be avoided during treatment with this drug. Thioctodar should not be administered simultaneously with dairy products containing calcium.

The drug is light-sensitive; therefore, vials should be removed from the packaging only immediately before use.

Advanced age (over 75 years) is a relative contraindication for intravenous administration of thioctic acid preparations.

Use during pregnancy or breastfeeding.

Thioctic acid is not recommended during pregnancy due to lack of adequate clinical data.

There are no data on the passage of thioctic acid into breast milk; therefore, its use during breastfeeding is not recommended.

Effect on the ability to drive or operate machinery.

Caution is advised when driving or operating other potentially hazardous machinery requiring high attention and rapid psychomotor reactions during treatment with this medicinal product.

Dosage and Administration

The dosage and duration of treatment are determined individually by a physician.

For severe parasthesia caused by diabetic polyneuropathy, intravenous administration of the drug is recommended at a dose of 10 ml to 20 ml per day, corresponding to 300–600 mg of thioctic acid daily. The injection solution should be administered for 2–4 weeks during the initial treatment phase. The contents of the vial should be diluted in 250 ml of 0.9% sodium chloride solution and infused intravenously over a period of not less than 30 minutes. Due to the sensitivity of the active substance to light, the infusion solution must be prepared immediately before use and protected from light exposure, for example by using aluminum foil. The prepared infusion solution may be stored for up to 6 hours provided it is protected from light.

Children

Thioktodar is not recommended for use in children due to lack of clinical experience with the drug in this patient population.

Overdose

In case of overdose, symptoms such as nausea, vomiting, and headache may occur. When very high doses of thioctic acid (from 10 to 40 g) are taken in combination with alcohol, severe intoxication may develop, potentially leading to a fatal outcome. The clinical picture of poisoning initially presents with psychomotor agitation or impaired consciousness, followed by generalized seizures and development of lactic acidosis. Consequences of intoxication may include hypoglycemia, shock, rhabdomyolysis, hemolysis, disseminated intravascular coagulation, bone marrow suppression, and multiorgan failure.

Treatment
In suspected cases of significant intoxication (>80 mg/kg body weight of thioctic acid), immediate hospitalization is indicated, along with standard supportive measures (e.g., induced emesis, gastric lavage, activated charcoal). Treatment of life-threatening complications such as generalized seizures and lactic acidosis, as well as other intoxication effects, should follow modern principles of intensive care and be conducted symptomatically. Currently, there is no data available regarding the usefulness of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic acid.

Side effects.

Central nervous system: after intravenous administration of the drug, sensations of heaviness in the head, headache, hot flushes, increased sweating, dyspnea, increased intracranial pressure, dizziness, seizures, visual disturbances and diplopia, as well as altered or impaired taste sensations have been observed. In most cases, all these manifestations resolve spontaneously.

Gastrointestinal tract: with rapid intravenous administration, nausea, vomiting, diarrhea, and abdominal pain have been observed, which resolve spontaneously.

Hematological system: petechial hemorrhages in mucous membranes/skin, platelet dysfunction, hypocoagulation, hemorrhagic rashes (purpura), thrombophlebitis.

Metabolic disturbances: due to enhanced glucose utilization, blood glucose levels may decrease in some cases, possibly causing symptoms resembling hypoglycemia, such as dizziness, increased sweating, headache, and visual disturbances.

Immune system: autoimmune insulin syndrome (see section "Special precautions"), allergic reactions including skin rashes, urticaria, pruritus, eczema, as well as systemic reactions up to anaphylactic shock.

Cardiovascular system: with rapid intravenous administration, chest pain and tachycardia may occur, which resolve spontaneously.

Hepatobiliary system: cholestatic hepatitis.

Other: injection site reactions, weakness.

Shelf life.

3 years.

Storage conditions.

Keep out of reach of children!

Store in the original packaging at a temperature not exceeding 30°C. Do not freeze!

Incompatibilities.

Thiogammar reacts in vitro with ionic metal complexes (e.g., cisplatin), thus potentially reducing their efficacy. Thiogammar forms poorly soluble complex compounds with sugars. Therefore, the injectable solution Thiogammar is incompatible with glucose, fructose, and Ringer's solutions. The drug is also incompatible with solutions containing substances that react with SH-groups or disulfide bonds. For dilution, use only 0.9% sodium chloride solution.

Packaging.

Injectable solution, 10 ml in vials, pack of 5, pack of 10.

Prescription category.

Prescription only.

Manufacturer.

JSC "Insulin Production Plant "INDAR".

Manufacturer's address and place of business.

5 Zroshuvalna St., Kyiv, 02099, Ukraine. Tel.: 566-66-72.