Berlithion^®600 (Concentrate) Instructions for Use

Marketing Authorization Holder

Berlin-Chemie/Menarini Pharma, GmbH (Germany)

Manufactured By

Siegfried Hameln, GmbH (Germany)

ATC Code

A16AX01 (Thioctic acid)

Active Substance

Thioctic acid (BAN)

Dosage Form

Berlithion® 600

Concentrate for solution for infusion 25 mg/1 ml: amp. 24 ml 5 pcs.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion greenish-yellow in color, transparent.

Excipients: ethylenediamine – 0.155 mg, water for injections – up to 24 mg.

24 ml – amber glass ampoules of 25 ml volume (5) with a white break-line indicator mark and three stripes (green-yellow-green) – plastic trays (1) – cardboard cartons.

Clinical-Pharmacological Group

Drug with antioxidant action, regulating carbohydrate and lipid metabolism

Pharmacotherapeutic Group

Metabolic agent

Pharmacological Action

Thioctic (alpha-lipoic) acid is an endogenous antioxidant with direct (binds free radicals) and indirect action. It is a coenzyme in the decarboxylation reactions of alpha-keto acids. It helps to reduce plasma glucose concentration and increase liver glycogen concentration, also reduces insulin resistance, participates in the regulation of carbohydrate and lipid metabolism, and stimulates cholesterol metabolism.

Due to its antioxidant properties, Thioctic acid protects cells from damage by their breakdown products, reduces the formation of advanced glycation end products in nerve cells in diabetes mellitus, improves microcirculation and endoneural blood flow, and increases the physiological content of the antioxidant glutathione.

By helping to reduce plasma glucose concentration, it affects alternative glucose metabolism in diabetes mellitus, reduces the accumulation of pathological metabolites in the form of polyols, and thereby reduces nerve tissue edema. Due to its participation in fat metabolism, Thioctic acid increases the biosynthesis of phospholipids, in particular phosphoinositides, thereby improving the damaged structure of cell membranes; it normalizes energy metabolism and nerve impulse conduction.

Thioctic acid eliminates the toxic effects of alcohol metabolites (acetaldehyde, pyruvic acid), reduces the excessive formation of free oxygen radical molecules, reduces endoneural hypoxia and ischemia, alleviating the manifestations of polyneuropathy in the form of paresthesia, burning sensation, pain, and numbness of the extremities.

Thus, Thioctic acid has antioxidant, neurotrophic effects, and improves lipid metabolism.

The use of thioctic acid in the form of an ethylenediamine salt helps to reduce the severity of possible side effects.

Pharmacokinetics

After IV administration of thioctic acid, the C_max in plasma after 30 minutes is about 20 µg/ml, AUC is about 5 µg/h/ml. It has a first-pass effect through the liver. Metabolite formation occurs as a result of side chain oxidation and conjugation. V_d is about 450 ml/kg. Total plasma clearance is 10-15 ml/min/kg. It is excreted by the kidneys (80-90%), mainly as metabolites. T_1/2 is about 25 minutes.

Indications

• Diabetic polyneuropathy;
• Alcoholic polyneuropathy.

ICD codes

Dosage Regimen

The drug is intended for infusion administration.

At the beginning of treatment, it is administered IV drip at a daily dose of 600 mg (1 ampoule).

Before use, the contents of 1 ampoule (24 ml) are diluted in 250 ml of 0.9% sodium chloride solution and administered IV drip, slowly, over at least 30 minutes. Due to the photosensitivity of the active substance, the infusion solution should be prepared immediately before use.

The course of treatment is 2-4 weeks. For subsequent maintenance therapy, thioctic acid is used in oral form at a daily dose of 300-600 mg. The duration of the treatment course and the need for its repetition are determined by the doctor.

Adverse Reactions

Possible side effects of the drug are listed below in descending order of frequency: common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated reports. No correlation between the frequency of side effects and patient gender or age has been observed.

Nervous system disorders very rarely – change or disturbance of taste sensations, diplopia, convulsions.

Blood and lymphatic system disorders very rarely – thrombocytopathy, hemorrhagic rash (purpura), thrombophlebitis.

Metabolism and nutrition disorders very rarely – decrease in plasma glucose concentration (due to improved glucose utilization). Complaints indicative of a hypoglycemic state (dizziness, sweating, headache, and visual impairment) have been reported.

Immune system disorders very rarely – allergic reactions such as skin rash, urticaria, itching; in isolated cases – anaphylactic shock.

Local reactions very rarely – burning sensation at the injection site.

Other with rapid IV administration, spontaneously resolving increased intracranial pressure (feeling of heaviness in the head) and difficulty breathing have been observed.

Contraindications

• Hypersensitivity to thioctic acid or other components of the drug in the medical history;
• Age under 18 years (efficacy and safety of the drug use have not been established);
• Pregnancy (insufficient experience with the use of the drug);
• Breastfeeding period (insufficient experience with the use of the drug).

Use in Pregnancy and Lactation

Due to the lack of sufficient clinical experience with the use of thioctic acid during pregnancy and breastfeeding, the use of the drug in the corresponding category of patients is not recommended.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Special Precautions

In patients with diabetes mellitus, constant monitoring of plasma glucose concentration is necessary, especially at the initial stage of therapy with the drug. In some cases, it may be necessary to reduce the dose of insulin or oral hypoglycemic agents to avoid the development of hypoglycemia.

Alcohol consumption reduces the effectiveness of treatment with thioctic acid, so patients should refrain from drinking alcohol during the entire course of therapy with the drug, and also, if possible, during the intervals between courses.

With parenteral use, hypersensitivity reactions may occur. If symptoms of hypersensitivity (itching, malaise) appear, the administration of the drug should be stopped immediately.

The solvent for the drug can only be 0.9% sodium chloride solution. The freshly prepared infusion solution must be protected from light, for example, with aluminum foil. The light-protected solution can be stored for approximately 6 hours.

Effect on ability to drive vehicles and operate machinery

The effect of thioctic acid on the speed of psychomotor reactions and the ability to perceive or assess a situation has not been specifically studied, therefore, during treatment with the drug, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Since Thioctic acid can form chelate complexes with metals, simultaneous administration with iron preparations should be avoided.

Simultaneous use of the drug with cisplatin reduces the effectiveness of the latter.

Thioctic acid forms poorly soluble complex compounds with sugar molecules. The drug is incompatible with glucose, fructose and dextrose solutions, Ringer’s solution, as well as with solutions that react with disulfide and SH-groups.

The drug enhances the hypoglycemic effect of insulin and oral hypoglycemic agents when used concomitantly.

Ethanol significantly reduces the therapeutic effectiveness of thioctic acid.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.