Tio-lipon–novopharm

INSTRUCTION for medical use of the medicinal product TIO-LIPON-NOVOFARM (TIO-LIPON-NOVOFARM)

Composition:

Active substance: thioctic (α-lipoic) acid;

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

Excipients: meglumine, macrogol 300, water for injections.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear yellow or yellowish-green solution.

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

Pharmacological properties.

Pharmacodynamics.

Thioctic (α-lipoic) 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 reduction of blood glucose levels and increases glycogen content in the liver. Deficiency or impaired metabolism of thioctic (α-lipoic) acid due to intoxications or excessive accumulation of certain breakdown products (e.g., ketone bodies) leads to impaired aerobic glycolysis. Thioctic (α-lipoic) acid can exist in two physiologically active forms (oxidized and reduced), both of which possess antitoxic and antioxidant effects.

Thioctic (α-lipoic) acid affects cholesterol metabolism, participates in the regulation of lipid and carbohydrate metabolism, and improves liver function (due to hepatoprotective, antioxidant, and detoxifying effects). Thioctic (α-lipoic) acid is pharmacologically similar to the B-group vitamins.

Pharmacokinetics.

Thioctic (α-lipoic) acid undergoes significant changes during first-pass metabolism in the liver. Considerable inter-individual variations in systemic availability of thioctic (α-lipoic) acid are observed. It is excreted by the kidneys predominantly as metabolites. Metabolite formation occurs via side chain oxidation and conjugation. The half-life of thioctic (α-lipoic) acid in blood serum is 10–20 minutes.

Clinical characteristics.

Indications.

Paresthesia in diabetic polyneuropathy.

Contraindications.

• Hypersensitivity to thioctic (α-lipoic) acid or to any of the excipients.
• Cardiac and respiratory failure.
• Acute phase of myocardial infarction.
• Acute cerebrovascular events.
• Chronic alcoholism and other conditions that may lead to lactic acidosis.

Interaction with other medicinal products and other forms of interaction.

Thioctic (α-lipoic) acid reacts with metal ion complexes (e.g., cisplatin), therefore the medicinal product may reduce the efficacy of cisplatin.

Thioctic (α-lipoic) acid forms poorly soluble complex compounds with sugar molecules.

Thioctic (α-lipoic) acid acts as a metal chelator; therefore, it should not be administered concomitantly with metals (e.g., iron or magnesium preparations).

Ethanol reduces the therapeutic efficacy of thioctic (α-lipoic) acid.

Special precautions for use.

When administering the medicinal product, light-protective black bags should be used; these are placed over the vial during intravenous administration of the drug.

Do not use any leftover medicinal product.

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

In the treatment of patients with diabetes mellitus, especially at the beginning of therapy, frequent monitoring of blood glucose is necessary. In some cases, it may be necessary to adjust the doses of antidiabetic agents to prevent hypoglycemia.

When administering the medicinal product 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 should be taken.

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

During treatment of polyneuropathy, due to regenerative processes, a transient increase in sensitivity may occur, accompanied by paresthesia with sensations of "crawling ants."

A certain limitation for intravenous administration of thioctic (α-lipoic) acid preparations is advanced age (over 75 years).

Patients with a specific human leukocyte antigen genotype (more commonly found in certain ethnicities such as Japanese, Korean, and Caucasian) are more susceptible to developing insulin autoimmune syndrome (a hormonal disorder affecting blood glucose regulation, characterized by pronounced hypoglycemia) during treatment with thioctic (α-lipoic) acid.

Warning: Patients taking thioctic (α-lipoic) acid preparations should refrain from alcohol consumption, as ethanol reduces the therapeutic efficacy of thioctic (α-lipoic) acid.

Regular alcohol consumption is a significant risk factor for the development and progression of neuropathy symptoms and may negatively affect the treatment process. Therefore, patients with diabetic polyneuropathy are generally advised, if possible, to abstain from alcohol consumption. Restrictions on alcohol intake also apply during intervals between treatment courses.

Use during pregnancy or breastfeeding.

There is insufficient experience with the use of the medicinal product 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 the medicinal product, 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 medicinal product should be administered as an intravenous infusion at a dose of 600 mg per day.

For this purpose, 20 ml of the solution (corresponding to 600 mg of thioctic (α-lipoic) acid) should be diluted in 50–250 ml of 0.9% sodium chloride solution. The intravenous infusion should be administered slowly—infusion duration must be at least 30 minutes.

The prepared infusion solution should be used immediately and protected from light using light-protective black bags.

At the beginning of treatment, the medicinal product should be administered intravenously for 1–2 weeks. Afterwards, maintenance therapy may be continued with oral formulations of thioctic (α-lipoic) acid at a daily dose of 600 mg.

Children

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

Overdose

Symptoms: nausea, vomiting, and headache may occur. When very high doses of thioctic (α-lipoic) acid (from 10 to 40 g) are used in combination with alcohol, severe intoxication may develop, potentially leading to fatal outcomes. The clinical picture of poisoning initially presents with psychomotor agitation or impaired consciousness, and subsequently progresses to generalized seizures and the 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 significant intoxication (> 80 mg/kg body weight of thioctic (α-lipoic) acid), immediate hospitalization is indicated, along with standard supportive measures (e.g., induced vomiting, gastric lavage, activated charcoal). Management 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 are no data on the usefulness of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic (α-lipoic) acid.

Side effects.

Central nervous system: In individual cases, changes or disturbances in taste sensation, headache, hot flashes, increased sweating, dyspnea, increased intracranial pressure, dizziness, seizures, visual disturbances, and diplopia have been observed. In most cases, all these manifestations resolve spontaneously.

Gastrointestinal tract: In individual cases, when the drug was administered intravenously rapidly, nausea, vomiting, diarrhea, and abdominal pain were observed, which resolved spontaneously.

Blood system: In individual cases, petechial hemorrhages into mucous membranes/skin, platelet function disorders, hypocoagulation, hemorrhagic rashes (purpura), and thrombophlebitis were observed.

Metabolic disorders: Due to improved glucose utilization, blood glucose levels may decrease in some cases, possibly leading to symptoms resembling hypoglycemia, such as dizziness, increased sweating, headache, and visual disturbances.

Immune system: In isolated cases, skin rashes, urticaria, pruritus, eczema, as well as systemic reactions up to the development of anaphylactic shock and insulin autoimmune syndrome, have been observed.

Cardiovascular system: When administered intravenously rapidly, chest pain and tachycardia may occur, which resolve spontaneously.

Other: In isolated cases, reactions at the injection site and weakness have been reported.

Shelf life: 3 years.

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

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

Incompatibility: The solution of thioctic (α-lipoic) acid is incompatible with glucose solution, Ringer's solution, and with solutions that may react with SH-groups or disulfide bonds.

Packaging: 10 ml or 20 ml in a vial; 5 vials in a blister pack; 1 or 2 blister packs in a cardboard box.

Prescription category: Prescription only.

Manufacturer: Limited liability company "Novopharm-Biosyntez".

Manufacturer's address and location of business activity:

38 Zhитомирська St., Zvyagel, Zhytomyr region, 11700, Ukraine.