Pharmalipon

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

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 physicochemical properties: clear yellow 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 a decrease in blood glucose levels and an increase in 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 can exist in two physiologically active forms (oxidized and reduced), both of which possess antitoxic and antioxidant properties.

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 B-group vitamins.

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. 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 interacts 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 metals (e.g., iron or magnesium preparations).

Thioctic (α-lipoic) acid may enhance the glucose-lowering effect of insulin and other antidiabetic agents; therefore, regular monitoring of blood glucose levels is recommended, especially 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 neuropathy 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; these are placed over the vial during intravenous administration of the medicinal product.

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 level.

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 required 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 taken.

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

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

Certain restrictions regarding intravenous administration of thioctic (α-lipoic) acid apply to elderly patients (aged 75 years and older).

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 affecting blood glucose regulation, 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 prescribed 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 high concentration 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 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 should be at least 30 minutes.

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

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

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 ranging from 10 g to 40 g of thioctic (α-lipoic) acid are used in combination with alcohol, severe intoxication may occur, potentially leading to a fatal outcome. The clinical picture of poisoning initially presents with psychomotor agitation or impaired consciousness; the subsequent course is characterized 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 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 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 are no data on the usefulness of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic (α-lipoic) acid.

Adverse Reactions

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

Central nervous system: in individual cases, altered or impaired taste sensations, headache, hot flushes, excessive sweating, dyspnea, increased intracranial pressure, dizziness, seizures, visual disturbances, and diplopia have been observed. In most cases, these symptoms resolve spontaneously.

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

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

Metabolic disturbances: due to improved glucose utilization, blood glucose levels may decrease in some cases, potentially leading to symptoms resembling hypoglycemia such as dizziness, excessive sweating, headache, and visual disturbances.

Immune system: in isolated cases, skin rashes, urticaria, pruritus, eczema, and systemic reactions up to anaphylactic shock have been observed.

Frequency not known: insulin autoimmune syndrome (see section "Special Warnings and Precautions for Use").

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

General disorders and administration site reactions: in isolated cases, reactions at the injection site and weakness have been reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

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

Incompatibilities.

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

Packaging.

20 ml in a vial; 5 vials in a blister pack in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Limited Liability Company "Novofarm-Biosyntez".

Manufacturer's address and location.

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

Marketing Authorization Holder. Limited Liability Company "SYSTEM PHARM".

Address of the Marketing Authorization Holder.

100/5 Shevchenka Street, city of Boryspil, Kyiv region, 08300, Ukraine.