Thioctic acid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT THIOCTIC ACID (THIOCTIC ACID)

Composition:

Active substance: thioctic acid (thioctic acid);

1 ml contains 12 mg of thioctic acid;

Excipients: meglumine, macrogol 300, water for injections.

Pharmaceutical form. Solution for infusion.

Main physicochemical properties: yellowish or greenish-yellow solution.

Pharmacotherapeutic group.
Agents affecting the digestive system and metabolic processes. ATC code A16AX01.

Pharmacological properties.

Pharmacodynamics.

Thioctic acid is a substance synthesized in the body and acts as a coenzyme in the oxidative decarboxylation of α-keto acids; it plays an important role in cellular energy production. It promotes a reduction in blood glucose levels and increases glycogen content in the liver. Deficiency or impaired metabolism of thioctic acid (α-lipoic acid) due to intoxications or excessive accumulation of certain breakdown products (e.g., ketone bodies) leads to impaired aerobic glycolysis. Thioctic acid exists in two physiologically active forms (oxidized and reduced), both of which exhibit antitoxic and antioxidant effects. Thioctic acid affects cholesterol metabolism, participates in the regulation of lipid and carbohydrate metabolism, and improves liver function (due to hepatoprotective, antioxidant, and detoxifying actions). Pharmacologically, thioctic acid is similar to B-group vitamins.

Pharmacokinetics.

Thioctic acid undergoes significant changes during its first pass through the liver. Considerable interindividual variability in systemic availability of thioctic acid is observed. It is excreted by the kidneys predominantly as metabolites. Metabolite formation occurs via side chain oxidation and conjugation. The elimination half-life of the drug from blood plasma is 10–20 minutes.

Clinical characteristics.

Indications.

Impaired sensation in diabetic polyneuropathy.

Contraindications.

Hypersensitivity to thioctic acid or to any of the other components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Thioctic acid may enhance the blood glucose-lowering effect of insulin and/or other antidiabetic agents; therefore, regular monitoring of blood glucose levels is recommended, especially at the beginning of treatment with thioctic acid (alpha-lipoic acid). In individual cases, to prevent symptoms of hypoglycemia, a reduction in the dose of insulin or oral antidiabetic agent may be necessary.

Ethanol reduces the therapeutic efficacy of thioctic acid.

Warning: regular alcohol consumption is a significant risk factor for the development and progression of the clinical picture of neuropathy and thus may negatively affect the treatment process. Therefore, patients with diabetic neuropathy are generally advised to abstain from alcohol consumption whenever possible. Restrictions on alcohol consumption also apply to intervals between treatment courses.

Special precautions for use

The main factor in the effective treatment of diabetic polyneuropathy is optimal correction of the patient's blood glucose levels.

When administering the drug 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 some cases, patients with poorly controlled or inadequately controlled diabetes mellitus and worsening general health may develop severe anaphylactic reactions associated with the use of the drug.

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

Intravenous administration of thioctic acid preparations has certain limitations in elderly patients (aged 75 years and older).

Cases of autoimmune insulin syndrome have been reported during treatment with thioctic acid. Patients with certain human leukocyte antigen (HLA) genotypes, such as HLA-DRB1*04:06 and HLA-DRB1*04:03, are more susceptible to developing autoimmune insulin syndrome (a hormonal disorder affecting blood glucose regulation, characterized by pronounced hypoglycemia) during treatment with thioctic acid. The HLA-DRB1*04:03 allele (odds ratio for susceptibility to autoimmune insulin syndrome 1.6) is primarily found in Caucasians and is more prevalent in Southern Europe than in Northern Europe; the HLA-DRB1*04:06 allele (odds ratio for susceptibility to autoimmune insulin syndrome 56.6) is predominantly observed in patients from Japan and Korea.

Autoimmune insulin syndrome should be considered in the differential diagnosis of spontaneous hypoglycemia in patients receiving thioctic acid.

Use during pregnancy or breastfeeding

There is insufficient experience with the use of the drug during pregnancy or breastfeeding; therefore, it should not be administered during these periods.

Ability to affect reaction speed when driving or operating machinery

During treatment with this drug, caution should be exercised when driving vehicles or engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reactions.

Administration and Dosage.

The medication should be administered directly from the vial (i.e., without diluent) as an intravenous infusion at a dose of 600 mg per day (the contents of 1 vial) for at least 30 minutes.

Since thioctic acid is light-sensitive, vials should be stored in the cardboard package until immediately before use.

At the beginning of the treatment course, the medication should be administered intravenously. The treatment course lasts 2–4 weeks.

For subsequent therapy, oral formulations of thioctic acid should be used at a daily dose of 300–600 mg.

Children.

The efficacy and safety of the medication in children have not been established; therefore, it should not be prescribed to this patient age group.

Overdose.

Symptoms: Possible nausea, vomiting, and headache. When very high doses of thioctic acid (from 10 to 40 g) are used in combination with alcohol, severe intoxication may occur, potentially leading to a fatal outcome. The clinical picture of poisoning initially manifests as psychomotor agitation or impaired consciousness, and subsequently progresses to generalized seizures and development of lactic acidosis. Consequences of intoxication may include hypoglycemia, shock, rhabdomyolysis, hemolysis, acute necrosis of skeletal muscles, disseminated intravascular coagulation, bone marrow suppression, and multiorgan failure.

Treatment. In case of suspected overdose or intoxication (ingestion of 6000 mg in adults or > 50 mg/kg body weight in children), immediate hospitalization is indicated, along with standard management measures (e.g., induced emesis, gastric lavage, activated charcoal administration). Treatment of life-threatening complications such as generalized seizures and lactic acidosis, as well as other consequences of intoxication, should follow modern principles of intensive care and be conducted symptomatically. To date, there is no data on the appropriateness of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic acid.

Adverse Reactions

Very common (≥ 10%), common (≥ 1% – < 10%), uncommon (≥ 0.1% – < 1%), rare (≥ 0.01% – < 0.1%), very rare (< 0.01% or frequency unknown).

Injection site reactions. Very rare cases of reactions at the injection site have been reported.

Immune system disorders: Frequency unknown: insulin autoimmune syndrome.

Hypersensitivity reactions: Allergic skin reactions, skin rashes, urticaria, pruritus, eczema, as well as systemic reactions up to the development of anaphylactic shock.

Central nervous system disorders: Very rare: altered or impaired taste sensation.

After intravenous administration of thioctic acid, seizures and double vision (diplopia) have been observed very rarely.

Blood and lymphatic system disorders: After intravenous administration of thioctic acid, hemorrhagic rashes (purpura) and thrombopathies have been observed very rarely.

General adverse reactions: With rapid intravenous administration, increased intracranial pressure and respiratory distress syndrome may very commonly occur; these symptoms resolve spontaneously.

Due to improved glucose utilization, blood glucose levels may decrease in some cases, and very rarely symptoms resembling hypoglycemia such as dizziness, excessive sweating, headache, and visual disturbances may occur.

Reporting of adverse reactions. Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibilities.

Thioctic acid reacts in vitro with ionic metal complexes (e.g., with cisplatin). Thioctic acid forms poorly soluble complex compounds with sugar molecules (e.g., levulose solution).

Thioctic acid solution is incompatible with glucose solution, Ringer's solution, and solutions that may react with SH-groups or disulfide bonds.

It must not be used concomitantly with preparations containing metals (e.g., iron, magnesium preparations).

If necessary, only saline solution may be used as a solvent for administration of the drug solution.

Packaging.

50 ml in vials; 5 vials in a blister pack; 2 blister packs in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Limited liability company "FARMEKS GROUP".

Manufacturer's address and location of business activity.

100, Shevchenka Street, Boryspil, Kyiv Oblast, Ukraine, 08301.