LIPOTYON

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIPOTION (LIPOTION)

Composition:

Active substance: thioctic (α-lipoic) acid;

1 vial (50 mL) of solution contains 600 mg of thioctic (α-lipoic) acid;

Excipients: trometamol, sodium chloride, 1M trometamol solution, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, light yellow solution.

Pharmacotherapeutic group.
Agents affecting the gastrointestinal tract and metabolic processes. Thioctic acid. ATC code A16AX01.

Pharmacological Properties.

Pharmacodynamics.

α-Lipoic acid is an endogenous vitamin-like substance that functions as a coenzyme in the oxidative decarboxylation of α-keto acids.

Hyperglycemia associated with diabetes mellitus leads to the accumulation of so-called "advanced glycation end-products." This process results in reduced endoneurial blood flow and endoneurial hypoxia and ischemia, accompanied by increased production of reactive oxygen species, which in turn damage peripheral nerves. Additionally, a decreased level of antioxidants such as glutathione is observed in peripheral nerves.

α-Lipoic acid intervenes in these processes, reducing the formation of advanced glycation end-products, improving endoneurial blood flow, and increasing physiological levels of antioxidants such as glutathione, which acts as a scavenger of reactive oxygen species in the diabetic nerve.

These effects observed in experimental studies support the theory that peripheral nerve function may be improved by α-lipoic acid. This particularly applies to sensory disturbances in diabetic polyneuropathy, manifested as dysesthesia and paresthesia, such as burning sensations, pain, numbness, and "pins and needles."

Pharmacokinetics.

Primary metabolism of α-lipoic acid occurs in the liver. There are no significant differences in systemic availability of α-lipoic acid among different patients. α-Lipoic acid undergoes biotransformation via oxidation of side chains and conjugation, and is predominantly excreted by the kidneys.

The elimination half-life of α-lipoic acid in human plasma is approximately 25 minutes, and total plasma clearance is 10–15 ml/min per kilogram. At the end of a 12-minute infusion of 600 mg, plasma concentration reaches approximately 47 μg/ml. Animal studies (rats, dogs) using radiolabeled compounds have shown that excretion is primarily renal, with 80–90% recovered as metabolites. Similarly, in humans, only a small fraction of unchanged substance is found in urine. Biotransformation occurs mainly via oxidation of side chains (beta-oxidation) and/or S-methylation of the corresponding thiol groups.

Clinical characteristics.

Indications.

Treatment of symptoms of peripheral (sensorimotor) diabetic polyneuropathy.

Contraindications.

Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly, thioctic acid reduces the efficacy of cisplatin.

When used concomitantly with thioctic acid, the blood glucose-lowering effect of insulin and/or other antidiabetic agents may be enhanced. In cases of concomitant use of these medicinal products, especially at the beginning of treatment, regular monitoring of blood glucose levels should be performed. To prevent symptoms of hypoglycemia, in some cases it may be necessary to reduce the dose of insulin and/or oral antidiabetic agent.

Caution.

Regular alcohol consumption is a significant risk factor for the development and progression of the clinical picture of neuropathy and may thus negatively affect the treatment process with thioctic acid. Therefore, patients with diabetic polyneuropathy are generally advised, whenever possible, to abstain from alcohol consumption. This restriction also applies to intervals between treatment courses.

Special precautions for use

Hypersensitivity reactions of varying severity, up to anaphylactic shock, have been observed with parenteral administration of thioctic acid (see section "Adverse reactions"). Patients should be under close medical supervision during administration of the medicinal product. If first signs (such as itching, nausea, weakness) appear, treatment must be discontinued immediately and appropriate medical measures should be taken if necessary.

An unusual odor of urine may occur after administration of thioctic acid; however, this phenomenon is clinically insignificant.

Autoimmune insulin syndrome (AIS) has been reported during treatment with thioctic acid. Patients with human leukocyte antigen genotypes such as HLA-DRB1*04:06 and HLA-DRB1*04:03 alleles are more susceptible to developing AIS. The HLA-DRB1*04:03 allele (susceptibility to AIS: 1.6) has been particularly observed in Caucasians, with higher prevalence in Southern than in Northern Europe, and the HLA-DRB1*04:06 allele (susceptibility to AIS: 56.6) has been particularly observed in Japanese and Korean patients. AIS should be considered in the differential diagnosis of spontaneous hypoglycemia in patients receiving this medicinal product (see section "Adverse reactions").

The medicinal product contains 52.487 mg/flacon of sodium; therefore, caution should be exercised when administering it to patients on a sodium-restricted diet.

Use during pregnancy or breast-feeding

The medicinal product is not recommended during pregnancy due to the lack of adequate clinical data.

There are no data on the passage of thioctic acid into breast milk; therefore, the medicinal product is not recommended during breast-feeding.

Ability to influence the speed of reactions when driving or operating machinery

Thioctic acid has no effect or has a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The medicinal product is intended for intravenous administration.

The basis of treatment for diabetic polyneuropathy is optimal glycemic control.

Dosing

For adult patients with symptoms of peripheral (sensorimotor) diabetic polyneuropathy, the recommended daily dose is 50 ml of injection solution (corresponding to 600 mg of thioctic acid per day) administered intravenously.

During the initial treatment period, the injection solution should be administered intravenously for 2–4 weeks.

Method of Administration

The medicinal product should be administered directly from the vial (i.e., without dilution) as an intravenous infusion to adults at a dose of 600 mg per day (the contents of 1 vial) over a period of at least 30 minutes.

Intravenous administration may also be performed using an injection syringe over a period of not less than 12 minutes.

Infusion Guidelines

Since α-lipoic acid is light-sensitive, vials should be stored in their original packaging until immediately prior to use.

It is recommended to continue treatment with thioctic acid in oral formulations at a daily dose of 600 mg.

Children

The medicinal product should not be used in children.

Overdose

Symptoms

In cases of overdose, symptoms such as nausea, vomiting, and headache may occur.

Following accidental or intentional administration of thioctic acid in doses of 10–40 g in combination with alcohol intoxication, isolated cases with severe signs of intoxication, including fatal outcomes, have been observed. Clinical manifestations of intoxication included psychomotor disturbances or dizziness, followed by generalized seizures and the development of lactic acidosis. Consequences of thioctic acid intoxication include hypoglycemia, shock, rhabdomyolysis, hemolysis, disseminated intravascular coagulation (DIC), bone marrow suppression, and multiorgan failure.

Treatment

In suspected cases of significant intoxication with thioctic acid (e.g., more than 10 tablets of 600 mg in adults or more than 50 mg/kg body weight in children), the patient should be immediately hospitalized and standard measures for managing intoxication initiated (induction of emesis, gastric lavage, administration of activated charcoal). Treatment of generalized seizures, lactic acidosis, and other life-threatening consequences of intoxication should follow principles of modern intensive care and be directed toward symptomatic management.

To date, no advantage of hemodialysis, hemoperfusion, or filtration methods in the forced elimination of thioctic acid has been demonstrated.

Adverse Reactions

Adverse reactions that may occur during the use of thioctic acid are classified according to the following frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders:

Very rare – thrombopathy.

Immune system disorders:

Frequency not known – allergic reactions such as skin rash, urticaria, eczema, pruritus; anaphylactic reactions, autoimmune insulin syndrome (see section "Special precautions for use").

Metabolism and nutrition disorders:

Very rare – hypoglycaemia*.

Nervous system disorders:

Uncommon – dysgeusia; very rare – stroke, headache*, dizziness*, increased sweating*.

Eye disorders:

Very rare – diplopia, visual disturbances.

Gastrointestinal disorders:

Uncommon – nausea and vomiting.

Skin and subcutaneous tissue disorders:

Very rare – purpura.

General disorders and administration site conditions:

Very rare – reactions at the injection site.

After rapid intravenous injection, a sensation of pressure in the head and breathing difficulties may occur, which resolve spontaneously.

*Due to improved glucose utilization, a decrease in blood glucose levels may be observed very rarely. Consequently, symptoms of hypoglycaemia such as dizziness, increased sweating, headache, and blurred vision have been reported.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is important. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 25 °C, protected from light and kept out of reach of children.

Incompatibilities

Thioctic acid reacts in vitro with metal ion complexes (e.g., cisplatin). Thioctic acid forms complexes with sugar molecules (e.g., levulose solution).

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

As a carrier solution for infusions, only 0.9% sodium chloride solution should be used.

Packaging

50 ml in a vial; 1 vial in a light-protective container; 1 light-protective container in a cardboard box.

Prescription status

Prescription only.

Manufacturer

UORLD MEDICIN ILAC SAN. VE TIC. A.S./
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address

COSB G.O.Pasa Mah. 6. Cad. No:30, Cerkezkoy/Tekirdag, Turkey.

Marketing Authorization Holder

WORLD MEDICINE, LLC, Ukraine.