Pharmalipon® turbo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PHARMALIPON® TURBO (PHARMALIPON TURBO)

Composition:

Active substance: thioctic (α-lipoic) acid;

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

Excipients: meglumine, polyethylene glycol 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 (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 hepatic glycogen content. 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 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 variability in systemic availability of thioctic (α-lipoic) acid is observed. It is excreted primarily by the kidneys, mostly in the form of metabolites. Metabolite formation occurs through side-chain oxidation and conjugation. The elimination half-life of thioctic (α-lipoic) acid from blood serum is 10–20 minutes.

Clinical characteristics.

Indications.

Sensory disturbances 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, dehydration, 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 interacts in vitro with metal ion complexes (e.g., with cisplatin); therefore, there have been reports of reduced efficacy of cisplatin 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 metals (e.g., iron or magnesium-containing 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, especially at the beginning of thioctic (α-lipoic) acid therapy. 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 the clinical picture of neuropathy and may thus interfere with treatment efficacy. Therefore, patients with diabetic polyneuropathy are generally advised to abstain from alcohol consumption. The restriction on alcohol intake also applies during treatment-free intervals.

Special precautions for use

When administering the medicinal product, light-protective black bags must 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.

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

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 dosage of antidiabetic agents to prevent hypoglycemia.

During treatment of polyneuropathy, due to regenerative processes, transient increased sensitivity may occur, accompanied by paresthesia with a sensation 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 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 regulating blood glucose, characterized by pronounced hypoglycemia) during treatment with thioctic (α-lipoic) acid. The HLA-DRB1*04:03 allele (susceptibility ratio for 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 (susceptibility ratio for autoimmune insulin syndrome — 56.6) occurs predominantly in patients from Japan and Korea.

In patients receiving thioctic (α-lipoic) acid, autoimmune insulin syndrome should be considered in the differential diagnosis of spontaneous hypoglycemia.

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.

Effect on ability to drive or operate machinery

During treatment with the medicinal product, caution should be exercised when driving vehicles or operating other machinery that requires heightened attention and rapid psychomotor reactions.

Administration and Dosage

The medicinal product is administered directly from the vial (i.e., without diluent) as an intravenous infusion over at least 30 minutes at a dose of 600 mg daily (contents of 1 vial) in adults.

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

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

For further therapy, oral formulations of thioctic (α-lipoic) acid should be used at a dose of 300–600 mg per day.

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 nausea, vomiting, and headache. When very high doses ranging from 10 to 40 g of thioctic (α-lipoic) acid are used in combination with alcohol, severe intoxication may occur, potentially leading to 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, 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 supportive measures (e.g., induced emesis, gastric lavage, activated charcoal). Management of generalized seizures, lactic acidosis, and other life-threatening 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 (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 sensation, 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 after rapid intravenous administration of the drug; these symptoms usually resolve spontaneously.

Hepatobiliary disorders.

Frequency not known: cholestatic hepatitis.

Blood and lymphatic system disorders.

In individual cases, petechial hemorrhages in mucous membranes/skin, hypocoagulation, and 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, and visual disturbances.

Cardiovascular disorders.

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

General disorders and administration site conditions.

Common: after 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 the medicinal product has been authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to 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 solution is incompatible with glucose solution, Ringer's solution, and solutions that may react with SH-groups or disulfide bonds.

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

Packaging. 50 ml in a vial; 10 vials in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Limited liability company "Novofarm-Biosyntez".

Manufacturer's address and location of business activity.

38 Zhитomirska St., city of Zvyahel, Zvyahel district, Zhytomyr region, 11700, Ukraine.