DIALIPON®

INSTRUCTIONS for medical use of the medicinal product DIALIPON® (DIALIPON)

Composition:

Active substance: thioctic acid;

1 ml of solution contains 58.382 mg of meglumine salt of alpha-lipoic acid, which corresponds, recalculated to 100% substance, to 30 mg of alpha-lipoic acid;

Excipients: meglumine (N-methylglucamine), polyethylene glycol 300 (macrogol 300), water for injections.

Pharmaceutical form. Infusion solution.

Main physicochemical characteristics: clear yellow liquid.

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

Pharmacological properties.

Pharmacodynamics.

Thioctic acid is a vitamin-like substance produced in the body that functions as a coenzyme in the oxidative decarboxylation of α-keto acids. Hyperglycemia caused by diabetes leads to glucose deposition on vascular matrix proteins and the formation of advanced glycation end-products (AGEs). This process results in reduced endoneurial blood flow and endoneurial hypoxia/ischemia, associated with increased generation of free oxygen radicals that damage nerves, as well as depletion of the antioxidant glutathione in peripheral nerves. In studies on rats, thioctic acid influenced the biochemical processes induced by streptozotocin-induced diabetes, reducing the formation of advanced glycation end-products, improving endoneurial blood flow, and increasing physiological glutathione levels, which acts as an antioxidant against free radicals in nerves affected by diabetes. These experimentally observed effects suggest that thioctic acid may improve peripheral nerve function. This particularly applies to sensory disturbances occurring in polyneuropathy, which may manifest as dysesthesias and paresthesias, such as burning sensations, pain, numbness, or tingling. A study investigating the efficacy of thioctic acid in the symptomatic treatment of diabetic polyneuropathy confirmed beneficial effects of thioctic acid on symptoms including paresthesia, burning sensation, numbness, and pain.

Pharmacokinetics.

Thioctic acid undergoes substantial first-pass hepatic metabolism. Systemic bioavailability shows considerable individual variability. Thioctic acid is biotransformed via oxidation of the side chain and conjugation; 80–90% of its metabolites are excreted by the kidneys. The elimination half-life of thioctic acid is 25 minutes, and total plasma clearance is 10–15 ml/min/kg. After a 30-minute infusion of 600 mg thioctic acid, its plasma concentration reaches approximately 20 μg/ml. Only a negligible amount of unchanged substance is excreted in urine.

Clinical characteristics.

Indications.

Paresthesia in diabetic polyneuropathy.

Contraindications.

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

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 acid reacts with ionic metal complexes (e.g., with cisplatin), therefore the drug may reduce the efficacy of cisplatin.

Thioctic acid forms poorly soluble complex compounds with sugar molecules.

Thioctic acid is a metal chelator; therefore, it should not be used concomitantly with metals (iron, magnesium-containing preparations).

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 thioctic acid treatment. To prevent symptoms of hypoglycemia, in some cases it may be necessary to reduce the dose of insulin and/or oral antidiabetic agent.

Ethanol reduces the therapeutic efficacy of thioctic acid.

Special precautions for use.

When administering thioctic acid parenterally, there is a risk of allergic reactions, including anaphylactic shock; therefore, patients must be under appropriate medical supervision. If symptoms occur (e.g., itching, nausea, malaise), administration of the drug should be stopped immediately and appropriate therapeutic measures should be initiated.

Severe anaphylactic reactions associated with the use of DIALIPON® have been reported in individual patients with decompensated or inadequately controlled diabetes and worsening general health condition.

Cases of autoimmune insulin syndrome (AIS) have been reported during treatment with thioctic acid. Patients with human leukocyte antigen genotype (alleles HLA-DRB1*04:06 and HLA-DRB1*04:03) are more susceptible to developing AIS during thioctic acid therapy. The HLA-DRB1*04:03 allele (AIS susceptibility coefficient – 1.6) is particularly prevalent among Caucasian populations (higher in Southern Europe than in Northern Europe), while the HLA-DRB1*04:06 allele (AIS susceptibility coefficient – 56.6) is especially common in Japanese and Korean patients.

AIS should be considered in the differential diagnosis of spontaneous hypoglycemia in patients receiving thioctic acid treatment.

The key factor in effective treatment of diabetic polyneuropathy is optimal blood glucose control. Diabetic patients, especially at the beginning of treatment, require frequent monitoring of blood glucose levels. In some cases, doses of antidiabetic agents may need to be adjusted to prevent hypoglycemia. During treatment of polyneuropathy, transient increased sensitivity due to regenerative processes may occur, manifesting as paresthesia with a sensation of "pins and needles."

Regular alcohol consumption is a significant risk factor for the development and progression of neuropathic symptoms and may thus interfere with the effectiveness of DIALIPON® solution therapy. Therefore, patients with diabetic polyneuropathy are strongly advised to abstain from alcohol consumption. This recommendation also applies to periods when therapy is not being administered.

The drug is light-sensitive; therefore, ampoules should be removed from the packaging only immediately before use.

Advanced age (over 75 years) represents a relative limitation for intravenous administration of thioctic acid preparations.

Use during pregnancy or breastfeeding.

Thioctic acid is not recommended during pregnancy due to lack of adequate clinical data.

There are no data on the passage of thioctic acid into breast milk; therefore, its use during breastfeeding is not recommended.

Ability to affect reaction speed when driving or operating machinery.

Caution is required when driving vehicles or engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reactions during treatment with this drug.

Method of Administration and Dosage.

The dosage and duration of treatment are determined individually by a physician.

For severe paresthesia, intravenous administration of the drug is recommended at a dose of 10 to 20 mL per day, corresponding to 300–600 mg of thioctic acid per day. The infusion solution should be used for 2–4 weeks during the initial treatment phase. The ampoule contents should be diluted in 250 mL of 0.9% sodium chloride solution and administered intravenously, with the infusion lasting no less than 30 minutes. Due to the active substance's sensitivity to light, the infusion solution must be prepared immediately before administration and protected from light exposure, for example, by using aluminum foil. The prepared infusion solution may be stored for up to 6 hours, provided it is protected from light.

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

Children.

Dialipon® is not recommended for use in children and adolescents due to the lack of clinical experience with the drug in this patient population.

Overdose.

In case of overdose, symptoms such as nausea, vomiting, and headache may occur. When very high doses of thioctic acid (from 10 to 40 g) are taken in combination with alcohol, severe intoxication may develop, potentially leading to a fatal outcome. The clinical picture of poisoning initially presents with psychomotor agitation or impaired consciousness, and subsequently progresses to generalized tonic-clonic seizures and the development of lactic acidosis. Consequences of intoxication may include hypoglycemia, shock, rhabdomyolysis, hemolysis, disseminated intravascular coagulation, bone marrow suppression, and multiorgan failure.

Treatment. In suspected cases of significant intoxication (e.g., > 80 mg/kg body weight in adults), immediate hospitalization is indicated, along with standard supportive measures (e.g., induced emesis, gastric lavage, activated charcoal administration). Management of generalized seizures, lactic acidosis, and other life-threatening consequences of intoxication should follow modern principles of intensive care and be conducted symptomatically. Currently, there are no data available regarding the efficacy of hemodialysis, hemoperfusion, or hemofiltration for enhanced elimination of thioctic acid.

Adverse Reactions

Classification of adverse reaction frequencies:

Very common: ≥ 1/10;
Common: ≥ 1/100 to < 1/10;
Uncommon: ≥ 1/1000 to < 1/100;
Rare: ≥ 1/10000 to < 1/1000;
Very rare: < 1/10000;
Frequency not known: cannot be estimated based on available data.

Central nervous system:

Very rare: altered or impaired taste sensation, headache, hot flushes, increased sweating, dyspnea, increased intracranial pressure, dizziness, seizures, visual disturbances, and diplopia. In most cases, these manifestations resolve spontaneously.

Gastrointestinal tract:

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

Blood and lymphatic system disorders:

In individual cases, petechial hemorrhages in mucous membranes/skin, thrombophlebitis, and hypocoagulation were observed;
Very rare: hemorrhagic rashes (purpura), platelet function disorders.

Metabolism and nutrition disorders:

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

Immune system disorders:

Very rare: skin rashes, urticaria, pruritus, eczema, as well as systemic reactions up to the development of anaphylactic shock;
Frequency not known: autoimmune insulin syndrome (see section "Special precautions").

Cardiovascular system:

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

Reactions at the site of administration:

Very rare: reactions at the injection site, weakness.

Reporting suspected adverse reactions after drug registration is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 5 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of the reach of children.

Incompatibilities.

Dialipon® reacts in vitro with ionic metal complexes (e.g., with cisplatin), thus potentially reducing their efficacy. Dialipon® forms poorly soluble complex compounds with sugars; therefore, this infusion solution is incompatible with glucose, fructose, and Ringer's solution. The drug is incompatible with solutions containing substances that react with SH-groups or disulfide bridges. For dilution, use only 0.9% sodium chloride solution.

Packaging.

10 ml or 20 ml in an ampoule; packs of 5 or 10 ampoules.

5 ampoules in a blister; 1 or 2 blisters per pack.

Prescription status. Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.