Dialipon®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DIALIPON® (DIALIPON®)

Composition:

Active substance: thioctic acid;

1 capsule contains 300 mg (0.3 g) of alpha-lipoic acid;

Excipients: lactose monohydrate, microcrystalline cellulose, hypromellose (E15), colloidal anhydrous silicon dioxide, magnesium stearate.

Pharmaceutical form. Capsules.

Main physico-chemical characteristics: hard gelatin capsules size 0. Capsule body and cap are ivory-colored. The contents of the capsule is a yellow, powder-like granular mixture.

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

Pharmacological properties.

Pharmacodynamics.

Thioctic acid is an endogenous substance with vitamin-like activity that functions as a coenzyme and participates in the oxidative decarboxylation of α-keto acids. Hyperglycemia associated with diabetes mellitus leads to the non-enzymatic glycation of vascular matrix proteins and the formation of so-called "advanced glycation end-products" (AGEs). This process results in reduced endoneurial blood flow and endoneurial hypoxia/ischemia, which in turn leads to increased generation of oxygen-derived free radicals that damage peripheral nerves. A decrease in levels of antioxidants such as glutathione in peripheral nerves has also been observed.

Pharmacokinetics.

After oral administration, thioctic acid is rapidly absorbed. Due to extensive presystemic metabolism, the absolute bioavailability of thioctic acid is approximately 20%. Because of rapid tissue distribution, the plasma half-life of thioctic acid is approximately 25 minutes. The relative bioavailability of thioctic acid from solid oral dosage forms exceeds 60% compared to the oral solution. A maximum plasma concentration of approximately 4 μg/mL was measured about 30 minutes after oral administration of 600 mg thioctic acid. Only a small amount of unchanged substance is excreted in urine. Biotransformation occurs via oxidative shortening of the side chain (β-oxidation) and/or S-methylation of the corresponding thiols. In vitro, thioctic acid reacts with metal ion complexes, for example cisplatin, forming moderately soluble complexes with sugar molecules.

Clinical characteristics.

Indications.

Prevention and treatment of diabetic polyneuropathy.

Contraindications.

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

Interaction with other medicinal products and other forms of interaction.

The efficacy of cisplatin is reduced when administered concomitantly with Diaplipon®. Thioctic acid acts as a metal chelator; therefore, according to basic principles of pharmacotherapy, it should not be administered simultaneously with metal-containing compounds (e.g., dietary supplements containing iron or magnesium, or dairy products, which contain calcium). If the total daily dose of the drug is administered 30 minutes before breakfast, dietary supplements containing iron and magnesium should be taken during the day or in the evening.

In patients with diabetes mellitus, thioctic acid may enhance the blood glucose-lowering effect of insulin and oral antidiabetic agents. Therefore, especially during the initial phase of treatment, careful monitoring of blood glucose levels is recommended. In some cases, to avoid symptoms of hypoglycemia, a reduction in the dose of insulin or oral antidiabetic agents may be required.

Ethanol reduces the therapeutic efficacy of thioctic acid.

Special precautions for use

The main factor in effective treatment of diabetic polyneuropathy is optimal control of the patient's blood glucose levels. At the beginning of treatment for polyneuropathy, transient intensification of paresthesia with sensations of "pins and needles" may occur due to regenerative processes.

When using thioctic acid in patients with diabetes mellitus, frequent monitoring of blood glucose levels is required. In some cases, it may be necessary to reduce the doses of antidiabetic medications to prevent the development of hypoglycemia.

Regular consumption of alcohol is a significant risk factor for the development and progression of polyneuropathy and may interfere with successful treatment. Therefore, alcohol intake should be avoided during treatment and between treatment courses.

Dialipon® contains lactose; therefore, patients with known intolerance to certain sugars should consult their physician before taking this medicinal product.

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 (susceptibility coefficient for AIS development – 1.6) is particularly prevalent among individuals of Caucasian descent (more common in Southern Europe than in Northern Europe), while the HLA-DRB1*04:06 allele (susceptibility coefficient for AIS development – 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.

Use during pregnancy or breastfeeding

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

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

Ability to influence reaction speed when driving or operating machinery

During treatment, caution is required when driving, operating machinery, or engaging in other potentially hazardous activities requiring increased attention and psychomotor speed, due to the possibility of adverse reactions such as hypoglycemia (dizziness and visual disturbances).

Method of Administration and Dosage

Adults. The daily dose is 600 mg of thioctic acid (2 capsules of DiALIPON® 300 mg), to be taken once daily, 30 minutes before the first meal. The capsules must not be chewed and should be swallowed with sufficient fluid.

In cases of severe parasthesia, initial treatment should preferably begin with parenteral administration of DiALIPON® for injection solution for 2–4 weeks. This should then be followed by continuation of treatment with oral administration of the drug at a dose of 600 mg once daily.

The duration of treatment should be determined by the physician according to the nature and course of the disease.

Children.

The drug should not be administered to children, as there is insufficient clinical experience in this age group.

Overdose.

In cases of overdose, nausea, vomiting, and headache may occur. Following accidental ingestion or suicide attempts involving oral administration of thioctic acid in doses ranging from 10 g to 40 g in combination with alcohol, significant intoxications have been observed, in some cases resulting in death. In the initial phase, the clinical picture of intoxication may present as psychomotor agitation or impaired consciousness. This may be followed by generalized seizures and lactic acidosis. Additionally, high-dose thioctic acid intoxication has been associated with hypoglycemia, shock, acute skeletal muscle necrosis, hemolysis, disseminated intravascular coagulation syndrome, bone marrow suppression, and multiorgan failure.

Treatment. Even in suspected cases of severe intoxication with DiALIPON® (e.g., ingestion of more than 20 capsules of 300 mg in adults or a dose exceeding 50 mg/kg body weight in children), immediate hospitalization is recommended, along with measures according to general principles of acute poisoning management (e.g., induction of emesis, gastric lavage, administration of activated charcoal). Symptomatic treatment of life-threatening complications such as generalized seizures and lactic acidosis should be performed in accordance with principles of modern intensive care. To date, the benefit of hemodialysis, hemoperfusion, or other forced elimination techniques for removing thioctic acid has not been confirmed.

Adverse reactions.

Classification of frequency of adverse reactions:

very common: ≥ 1/10;

common: ≥ 1/100 – <1/10;

uncommon: ≥ 1/1000 – < 1/100;

rare: ≥ 1/10000 – < 1/1000;

very rare: <1/10000;

not known: cannot be determined from available data.

From the nervous system.

Very rare: alteration or disturbance of taste sensations.

From the gastrointestinal tract.

Common: nausea.

Very rare: vomiting, abdominal pain and gastrointestinal pain, diarrhea.

From the metabolism.

Very rare: decreased blood glucose level. Reports have been received of symptoms indicating hypoglycemic states, namely: dizziness, increased sweating, headache, and visual disturbances.

From the immune system.

Very rare: allergic reactions, including skin rash, urticaria (urticarial rash), pruritus, dyspnea.

Not known: autoimmune insulin syndrome.

Others.

Not known: eczema.

Shelf life. 2 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 reach of children.

Packaging. 10 capsules in a blister. 3 or 6 blisters per pack.

Prescription category. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.