Lipoika

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

Composition:

Active substance: thioctic (α-lipoic) acid;

One film-coated tablet contains 300 mg or 600 mg of thioctic (α-lipoic) acid;

Excipients: low-substituted hydroxypropylcellulose, hydroxypropylcellulose, magnesium stearate, Opadry Green 20A.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics:

300 mg tablets — round-shaped, film-coated, yellow-green in color, with a biconvex surface;

600 mg tablets — elongated in shape, film-coated, yellow-green in color, with a biconvex surface.

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

Pharmacological Properties

Pharmacodynamics

Thioctic acid (α-lipoic acid) acts as a coenzyme in the oxidative decarboxylation of α-keto acids. Hyperglycemia associated with diabetes mellitus leads to the accumulation of glucose on matrix proteins of blood vessels and to the formation of so-called "advanced glycation end-products" (AGEs). This process results in reduced endoneurial blood flow and endoneurial hypoxia/ischemia, accompanied by increased production of reactive oxygen species (free radicals), which cause damage to peripheral nerves.

Animal studies have shown that α-lipoic acid influences biochemical processes induced by streptozotocin-induced diabetes, improving endoneurial blood flow and increasing levels of the physiological antioxidant glutathione. Additionally, as an antioxidant, it reduces the concentration of reactive oxygen species (free radicals) in diabetic-affected nerves.

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

Pharmacokinetics

After oral administration, α-lipoic acid is rapidly absorbed. When tablets are administered, the absolute bioavailability of α-lipoic acid (measured as the parent substance) is approximately 20% compared to intravenous administration, indicating a significant first-pass effect. Due to rapid tissue distribution, the elimination half-life of α-lipoic acid is approximately 25 minutes. Similar to the oral solution, which serves as the reference standard formulation with maximum absorption, the absorption profile of tablets is characterized by a rapid influx of the active substance, accompanied by reduced inter-subject variability. The relative bioavailability (compared to the oral solution) is > 60%. A maximum plasma concentration of 4 μg/mL was observed approximately 0.5 hours after oral administration of 600 mg of α-lipoic acid. Animal experiments using radiolabeled tracers demonstrated that the drug is excreted predominantly via the kidneys (80–90%), mostly in the form of metabolites. In humans, only a negligible portion of the unchanged substance is excreted in urine. Biotransformation occurs primarily 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 or to any of the components of the medicinal product.

Interaction with other medicinal products and other types of interactions.

The efficacy of cisplatin is reduced when administered concomitantly with thioctic acid. Thioctic acid is a metal chelator; therefore, according to the 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 medicinal product is administered 30 minutes before breakfast, dietary supplements containing iron and magnesium should be taken at midday or in the evening.

Alpha-lipoic acid forms poorly soluble complexes with sugar molecules (e.g., with lavulose solution).

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 stage of treatment, careful monitoring of blood glucose levels is recommended. To avoid symptoms of hypoglycemia, in some cases, a dose reduction of insulin or oral antidiabetic agents may be required.

Caution. Regular alcohol consumption is a significant risk factor for the development and progression of the clinical picture of neuropathy; thus, a negative impact on the treatment process with Lipoyca is possible. Therefore, patients with diabetic polyneuropathy are advised to abstain from alcohol consumption. Restriction of alcohol intake also applies to intervals between treatment courses.

Special precautions for use

The main factor in effective treatment of diabetic polyneuropathy is optimal correction of the patient's blood glucose levels.

An unusual odor of urine may be noticed during the use of the medicinal product; however, this has no clinical significance.

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

There has been one reported case of autoimmune insulin syndrome (AIS) during treatment with α-lipoic acid. Patients with certain HLA genotypes (human leukocyte antigen system), such as HLA-DRB1*04:06 and HLA-DRB1*04:03 alleles, are more susceptible to developing AIS during treatment with α-lipoic acid. The HLA-DRB1*04:03 allele (relative risk ratio for possible susceptibility to AIS — 1.6) is predominantly found among individuals of Caucasian descent, with higher prevalence in Southern Europe compared to Northern Europe. The HLA-DRB1*04:06 allele (relative risk ratio for possible susceptibility to AIS — 56.6) is predominantly found in patients from Japan and Korea. The possibility of developing AIS should be considered in patients receiving α-lipoic acid when making a differential diagnosis of spontaneous hypoglycemia (see section "Adverse reactions").

Use during pregnancy or breastfeeding

The use of thioctic acid during pregnancy is not recommended due to the 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.

Studies on toxic effects on reproductive function have not shown any evidence of effects on fertility.

Ability to influence the reaction rate when driving or operating machinery

During treatment, caution should be exercised (due to the possible occurrence of adverse reactions such as dizziness and visual disturbances) when driving vehicles or engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Method of Administration and Dosage

The daily dose is 600 mg of thioctic acid, administered either as two 300 mg tablets or one 600 mg tablet. The medicinal product should be taken as a single daily dose 30 minutes before the first meal. The tablets should be taken on an empty stomach, without chewing, and swallowed with sufficient amount of water.

Concomitant food intake may impair the absorption of α-lipoic acid; therefore, it is recommended to administer the medicinal product 30 minutes before meals.

In cases of severe parasthesia, treatment may be initiated with the injectable form of the medicinal product Lipoica.

The duration of treatment is determined individually by the physician.

Children

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

Overdose

In case of overdose, nausea, vomiting, and headache may occur. Following accidental or intentional (suicidal intent) oral administration of thioctic acid in doses ranging from 10 g to 40 g in combination with alcohol, severe intoxications have been observed, in some cases resulting in death.

At the initial stage, the clinical picture of intoxication may present with psychomotor agitation or impaired consciousness. Subsequently, generalized seizures and lactic acidosis (lactic acid coma) may develop. In addition, hypoglycemia, shock, acute necrosis of skeletal muscles, hemolysis, disseminated intravascular coagulation syndrome, bone marrow suppression, and multiorgan failure have been reported following intoxication with high doses of thioctic acid.

Treatment. In suspected cases of severe intoxication with the medicinal product, immediate hospitalization is recommended, along with measures according to general principles of management in accidental poisoning (e.g., induction of emesis, gastric lavage, administration of activated charcoal). Treatment of life-threatening complications such as generalized seizures and lactic acidosis, as well as other consequences of intoxication, should be carried out in accordance with principles of modern intensive care. 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.

The following classification is used to assess the frequency of adverse reactions: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), frequency not known (cannot be estimated from the available data).

From the nervous system side.

Common: dizziness.

Very rare: taste alteration or disturbance, headache, hyperhidrosis.

From the eye organs side.

Very rare: visual disturbances.

From the gastrointestinal tract side.

Common: nausea.

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

From the metabolism and nutritional side.

Very rare: hypoglycemia.

From the immune system side.

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

Frequency not known: autoimmune insulin syndrome (see section "Special precautions for use"), eczema.

General disorders:

Very rare: decreased blood glucose levels associated with improved glucose uptake. Symptoms similar to hypoglycemia: dizziness, increased sweating, headache, and visual disturbances.

Reporting suspected adverse reactions.

Reporting suspected adverse reactions after the medicinal product has been registered is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report all suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 1.5 years.

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 pack; 3 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's name and address of the place of business.

13, Boryspylska Street, Kyiv, 02093, Ukraine.