Dialipon

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

Composition:

Active substance: thioctic acid (thioctic (α-lipoic) acid);

One tablet contains thioctic (α-lipoic) acid – 600 mg;

Excipients: low-substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate;

Film coating: hypromellose, titanium dioxide (E 171), polyethylene glycol, talc, yellow iron oxide (E 172).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, biconvex film-coated tablets of dull yellow-orange color with a bevel and a score line.

Pharmacotherapeutic group. Agents affecting the digestive system and metabolic processes. Thioctic acid. ATC code A16A X01.

Pharmacological Properties

Pharmacodynamics

α-Lipoic acid acts as a coenzyme in the oxidative decarboxylation of α-keto acids.

Hyperglycemia caused by diabetes mellitus leads to the accumulation of glucose on matrix proteins of blood vessels and the formation of so-called "advanced glycation end-products" (AGEs). This process results in reduced endoneurial blood flow and endoneurial hypoxia/ischemia, which is associated with increased production of reactive oxygen species (ROS). These free radicals contribute to damage of the peripheral nerve.

Animal studies have shown that α-lipoic acid influences biochemical processes induced by streptozotocin-induced diabetes, resulting in improved endoneurial blood flow and increased levels of the physiological antioxidant glutathione. As an antioxidant, α-lipoic acid also reduces the amount of reactive oxygen species in diabetic-affected nerves.

The effects observed in experimental studies suggest that peripheral nerve function may be improved by α-lipoic acid. This is relevant to sensory disturbances in diabetic polyneuropathy, which may manifest as paresthesia including burning sensations, pain, numbness, and "pins and needles."

Pharmacokinetics

After oral administration, α-lipoic acid is rapidly and almost completely absorbed from the gastrointestinal tract. Due to a significant first-pass effect, the absolute bioavailability of α-lipoic acid (defined as the parent substance) following oral administration is approximately 20% compared to intravenous administration. Due to rapid tissue distribution, the elimination half-life of α-lipoic acid is approximately 25 minutes. The relative bioavailability of α-lipoic acid (compared to an oral solution) is >60%. A maximum plasma concentration of 4 μg/mL was observed approximately 0.5 hours after oral intake of 600 mg of α-lipoic acid.

Animal experiments (in rats and dogs) using radiolabeled compounds demonstrated that the drug is excreted predominantly via the kidneys (80–90%), primarily in the form of metabolites. In humans, only a negligible portion of the unchanged substance is excreted in urine. Biotransformation occurs mainly through oxidative shortening of side chains (β-oxidation) and/or S-methylation of the corresponding thiols.

Clinical characteristics.

Indications.

Treatment of symptoms of peripheral (sensorimotor) diabetic polyneuropathy.

Contraindications.

Hypersensitivity to thioctic acid and to other components of the medicinal product.

Interaction with other medicinal products and other forms of interactions.

The efficacy of cisplatin is reduced when administered concomitantly with thioctic acid.

Thioctic acid is a metal chelator; therefore, it should not be administered together with metal-containing compounds (iron or magnesium preparations, or with dairy products, which contain calcium). If the daily dose of the medicinal product is taken 30 minutes before breakfast, iron- or magnesium-containing preparations should be taken at lunch or in the evening. α-Lipoic acid forms poorly soluble complexes with sugar molecules (e.g., lavulose solution).

When using the medicinal product DIALIPON**®** in patients with diabetes mellitus, an enhanced hypoglycemic effect of insulin and oral antidiabetic agents may occur. Therefore, especially during the initial stage of treatment, careful monitoring of blood glucose levels is recommended. In order to avoid symptoms of hypoglycemia, in some cases it may be necessary to reduce the dose of insulin or oral antidiabetic agents.

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 the medicinal product DIALIPON**®**. Therefore, patients with diabetic polyneuropathy are generally advised, whenever possible, to abstain from alcohol consumption. Restrictions on alcohol intake also apply during treatment-free intervals between therapy courses.

Special precautions for use

An unusual odor of urine may occur during administration of the drug; this is not of clinical significance.

At the beginning of treatment for polyneuropathy, a transient increase in paresthesia with a "pins and needles" sensation may occur due to regenerative processes.

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 or engaging in other potentially hazardous activities requiring high concentration and rapid psychomotor reactions due to the possibility of adverse reactions such as dizziness and visual disturbances.

Dosage and Administration.

For adult patients, one tablet of the medicinal product Dyalipon® (equivalent to 600 mg of α-lipoic acid) should be administered once daily. It should be taken approximately half an hour before the first meal.

The drug should be taken on an empty stomach, without chewing, and with sufficient amount of water. Taking the drug during meals may reduce the absorption of α-lipoic acid; therefore, it is recommended to take the entire daily dose half an hour before breakfast.

The duration of treatment is determined individually by a physician.

Children.

Since there are no data on the safety and efficacy of this drug in children, it is not recommended for use in this age group.

Overdose.

In case of overdose, nausea, vomiting, and headache may occur. After accidental ingestion or in suicide attempts involving oral administration of thioctic acid in doses ranging from 10 g to 40 g in combination with alcohol, severe intoxication has been observed, in some cases resulting in death. In the initial stage, the clinical picture of intoxication may present as psychomotor agitation or impaired consciousness. Subsequently, generalized seizures and lactic acidosis may develop. In addition, hypoglycemia, shock, acute skeletal muscle necrosis, hemolysis, disseminated intravascular coagulation syndrome, bone marrow suppression, and multiorgan failure have been reported in cases of intoxication with high doses of thioctic acid.

Treatment. In case of suspected severe intoxication, immediate hospitalization is recommended, along with measures according to general principles for accidental poisoning (e.g., inducing vomiting, gastric lavage, administration of activated charcoal). Treatment of life-threatening complications such as generalized seizures and lactic acidosis should be carried out in accordance with principles of modern intensive care; such treatment should be symptomatic. To date, the benefit of hemodialysis, hemoperfusion, or filtration methods with forced elimination of thioctic acid has not been confirmed.

Adverse Reactions

Gastrointestinal disorders:
Common – nausea;
in isolated cases – gastrointestinal disorders, including vomiting, abdominal pain and gastro-intestinal pain, diarrhea.

Allergic reactions:
in isolated cases – allergic reactions, including skin rash, urticaria (urticarial rash), pruritus and eczema.

Central nervous system disorders:
common – dizziness;
very rare – altered or impaired taste sensation.

Metabolic disorders:
in isolated cases – decreased blood glucose levels. Cases have been reported with symptoms suggestive of hypoglycemia (dizziness, increased sweating, headache, and visual disturbances).

Other:
dyspnea.

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 tablets in a blister. 3 or 6 blisters per carton.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.
74 Kyrylivska Street, Kyiv, 04080, Ukraine.