Tio-lipon-novopharm turbo

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT TIO-LIPON-NOVOFARM TURBO (TIO-LIPON-NOVOFARM TURBO)

Composition:

Active substance: thioctic acid;

1 ml of solution contains 12 mg of thioctic (α-lipoic) acid;

Excipients: meglumine, macrogol 300, water for injections.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: yellowish or greenish-yellow 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 that 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 (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 exists in two physiologically active forms (oxidized and reduced), both of which possess antitoxic and antioxidant effects. Thioctic (α-lipoic) acid influences 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 vitamin B complex.

Pharmacokinetics.

Thioctic (α-lipoic) acid undergoes significant changes during first-pass metabolism in the liver. Considerable interindividual variability in systemic availability of thioctic (α-lipoic) acid is observed. The substance is primarily excreted by the kidneys as metabolites. Metabolite formation occurs through side-chain oxidation and conjugation. The half-life of thioctic (α-lipoic) acid in blood serum is 10–20 minutes.

Clinical characteristics.

Indications.

Impaired sensation in diabetic polyneuropathy.

Contraindications.

Hypersensitivity to thioctic (α-lipoic) acid or to any of the excipients. Cardiac or respiratory failure, acute phase of myocardial infarction, acute cerebrovascular events, dehydration, chronic alcoholism and other conditions predisposing to lactic acidosis.

Interaction with other medicinal products and other forms of interaction.

Thioctic (α-lipoic) acid interacts in vitro with metal ion complexes (e.g. with cisplatin), and there have been reports of reduced cisplatin efficacy when administered concomitantly with this medicinal product.

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

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

Thioctic (α-lipoic) acid may enhance the blood glucose-lowering effect of insulin and other antidiabetic agents; therefore, regular monitoring of blood glucose levels is recommended, particularly at the beginning of treatment with thioctic (α-lipoic) acid. In some cases, it may be necessary to reduce the dose of insulin and/or oral antidiabetic agents to prevent symptoms of hypoglycemia.

Warning: Regular alcohol consumption is a significant risk factor for the development and progression of neuropathic symptoms and may thus interfere with treatment efficacy. Therefore, patients with diabetic polyneuropathy are generally advised to abstain from alcohol consumption. Restrictions on alcohol intake also apply during treatment-free intervals.

Special precautions for use.

When using the medicinal product, light-protective black bags must be used, which are placed over the vial during intravenous administration of the medicinal product.

Do not use any remaining medicinal product.

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

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 initiated.

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

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

During treatment of polyneuropathy, due to regenerative processes, a temporary 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).

Cases of autoimmune insulin syndrome (AIS) have been reported during treatment with thioctic (α-lipoic) 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, with pronounced hypoglycemia) during treatment with thioctic (α-lipoic) acid. The HLA-DRB1 * 04:03 allele (predisposition to AIS, odds ratio: 1.6) is more common in individuals of Caucasian descent (more prevalent in Southern Europe than in Northern Europe); the HLA-DRB1 * 04:06 allele (predisposition to AIS, odds ratio: 56.6) is predominantly found in patients from Japan and Korea. Autoimmune insulin syndrome should be considered in the differential diagnosis of spontaneous hypoglycemia in patients receiving thioctic (α-lipoic) 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 influence reaction speed when driving or operating machinery.

During treatment with the medicinal product, caution must 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 is administered directly from the vial (i.e., without a solvent) as an intravenous infusion over at least 30 minutes at a dose of 600 mg daily (the content of one vial) in adults.

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

At the beginning of the treatment course, the drug is administered intravenously. The treatment course lasts 2–4 weeks.

For subsequent therapy, oral formulations of thioctic (α-lipoic) acid are used at a daily dose of 300–600 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 of patients.

Overdose

Symptoms: Possible symptoms include nausea, vomiting, and headache. When very high doses of thioctic (α-lipoic) acid (from 10 to 40 g) are used in combination with alcohol, severe intoxication may occur, which can be fatal. The clinical picture of poisoning initially presents with psychomotor agitation or impaired consciousness, followed by 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 multi-organ 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., induction of emesis, gastric lavage, administration of 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 appropriateness of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic (α-lipoic) acid.

Adverse reactions.

Classification of the frequency of adverse reactions: very common: ≥ 1/10; common: ≥ 1/100 — < 1/10; uncommon: ≥ 1/1000 — < 1/100; rare: ≥ 1/10,000 — < 1/1000; very rare: < 1/10,000; frequency not known: cannot be estimated based on available data.

Immune system disorders.

Frequency not known: insulin autoimmune syndrome (see section "Special precautions").

Skin allergic reactions such as rash, urticaria, pruritus, eczema, as well as systemic reactions up to the development of shock may occur.

Central nervous system disorders.

Very rare: altered or impaired taste sensations, headache, hot flushes, increased sweating, dizziness, visual disturbances. After intravenous administration of thioctic (α-lipoic) acid, seizures and diplopia have been observed. In most cases, all these manifestations resolve spontaneously.

Frequency not known: loss of consciousness, seizures.

Gastrointestinal disorders.

In individual cases, nausea, vomiting, diarrhea, and abdominal pain have been observed following rapid intravenous administration of the drug, which resolve spontaneously.

Hepatobiliary disorders.

Frequency not known: cholestatic hepatitis.

Blood and lymphatic system disorders.

In individual cases, petechial hemorrhages in mucous membranes/skin, hypocoagulation, thrombophlebitis have been observed.

Very rare: hemorrhagic rashes (purpura), platelet function disorders.

Metabolic disorders.

Very rare: due to improved glucose utilization, blood glucose levels may decrease, possibly leading to symptoms resembling hypoglycemia such as dizziness, increased sweating, headache, visual disturbances.

Cardiac and vascular disorders.

Rapid intravenous administration may cause chest pain, tachycardia, which resolve spontaneously.

General disorders and administration site conditions.

Common: following rapid intravenous administration, increased intracranial pressure and respiratory distress syndrome, which resolve spontaneously, may occur.

Very rare: in isolated cases, reactions at the injection site and weakness have been reported.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life. 3 years.

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

Incompatibilities.

Thioctic (α-lipoic) acid interacts in vitro with ionic metal complexes (e.g., with cisplatin).

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

The medicinal product is incompatible with glucose solutions, Ringer's solution, and solutions that react with SH-groups or disulfide bonds.

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

Packaging.

50 ml in vials; 1 vial or 10 vials per cardboard pack.

Prescription category. Prescription only.

Manufacturer. Limited liability company "Novofarm-Biosyntez".

Manufacturer's address.

38 Zhитomirska St., city of Zvyagel, Zhytomyr region, 11700, Ukraine.