Instructions Berlition 600 IU concentrate for solution for infusions 600 IU ampoule 24 ml No. 5
Composition
active ingredient: thioctic acid;
1 ampoule (24 ml) of concentrate for solution for infusion contains 755 mg of thioctic acid ethylenediamine salt, which corresponds to 600 mg of thioctic acid;
excipient: water for injections.
Dosage form
Concentrate for solution for infusion.
Main physicochemical properties: transparent solution of greenish-yellow color.
Pharmacotherapeutic group
Other agents that affect the digestive system and metabolic processes, thioctic acid.
ATX code A16A X01.
Pharmacological properties
Pharmacodynamics
Thioctic acid is a vitamin-like substance that is formed in the body and acts as a coenzyme in the oxidative decarboxylation of a-keto acids. Hyperglycemia caused by diabetes mellitus leads to the deposition of glucose on the matrix proteins of blood vessels and the formation of advanced glycosylation end products. This process leads to a decrease in endoneural blood flow and endoneural hypoxia/ischemia, which is associated with increased formation of free oxygen radicals that damage the peripheral nerve, as well as depletion of the antioxidant glutathione in the peripheral nerves.
In studies on rats, thioctic acid affected the biochemical process caused by diabetes mellitus, which was provoked by streptozocin, which reduced the formation of advanced glycation end products, improved endoneural blood flow, increased the physiological content of glutathione, which acts in the nerve affected by the diabetic process, similar to the action of an antioxidant on free oxygen radicals. Such effects indicate the ability of thioctic acid to improve the function of peripheral nerves. This applies to sensory disorders in polyneuropathy, which can manifest themselves in the form of dysesthesias and paresthesias, such as, for example, a burning sensation, pain, a feeling of numbness or tingling.
In 1995, a multicenter placebo-controlled study was conducted on the effectiveness of thioctic acid for the symptomatic treatment of diabetic polyneuropathy, which obtained data on the beneficial effect of thioctic acid on such studied symptoms as paresthesia, burning sensation, numbness, and pain.
Pharmacokinetics
Thioctic acid has a pronounced first-pass effect through the liver. Systemic bioavailability is characterized by significant individual fluctuations. Thioctic acid is biotransformed by side-chain oxidation and conjugation and is excreted mainly by the kidneys. The half-life of thioctic acid in humans is approximately 25 minutes, and the total clearance in blood plasma is 10-15 ml/min/kg. After a 30-minute infusion of 600 mg of thioctic acid, its concentration in blood plasma is about 20 μg/ml. In experiments on animals (rats, dogs) using a radioactive label, it was possible to detect predominant renal excretion (80-90%), namely in the form of metabolites. In humans, only a small amount of the excreted intact substance is also found in the urine. Biotransformation occurs mainly by side chain oxidation (β-oxidation) and/or by S-methylation of the corresponding thiols.
Thioctic acid interacts in vitro with metal ion complexes (e.g. cisplatin). Thioctic acid forms poorly soluble complex compounds with sugar molecules.
Indication
Paresthesia in diabetic polyneuropathy.
Contraindication
History of hypersensitivity to the active substance or to any of the excipients of the medicinal product.
Interaction with other drugs and other types of interactions.
Thioctic acid interacts in vitro with metal ion complexes (e.g. cisplatin), therefore there have been reports of a decrease in the effect of cisplatin during simultaneous treatment with Berlition® 600 U.
With sugar molecules (for example, with a fructose solution), thioctic acid forms poorly soluble complex compounds.
Thioctic acid is a metal chelator, so it cannot be used together with metals (iron, magnesium preparations).
Thioctic acid may enhance the blood sugar-lowering effect of insulin and/or other antidiabetic agents, therefore, especially at the beginning of treatment with thioctic acid, regular monitoring of blood sugar levels is indicated. To prevent the appearance of symptoms of hypoglycemia, in individual cases it may be necessary to reduce the dose of insulin and/or oral antidiabetic agent.
Note:
Regular alcohol consumption is a significant risk factor for the onset and progression of the clinical picture of neuropathy and, therefore, may interfere with the effectiveness of treatment with Berlition® 600 IU. Therefore, patients with diabetic polyneuropathy are strongly advised to abstain from alcohol. This also applies to periods when therapy is not being carried out.
Interaction with other medicinal products and other types of interactions
With sugar molecules (for example, with a fructose solution), thioctic acid forms poorly soluble complex compounds.
Thioctic acid is a metal chelator, so it cannot be used together with metals (iron, magnesium preparations).
Thioctic acid may enhance the blood sugar-lowering effect of insulin and/or other antidiabetic agents, therefore, especially at the beginning of treatment with thioctic acid, regular monitoring of blood sugar levels is indicated. To prevent the appearance of symptoms of hypoglycemia, in individual cases it may be necessary to reduce the dose of insulin and/or oral antidiabetic agent.
Note:
Regular alcohol consumption is a significant risk factor for the onset and progression of the clinical picture of neuropathy and, therefore, may interfere with the effectiveness of treatment with Berlition® 600 IU. Therefore, patients with diabetic polyneuropathy are strongly advised to abstain from alcohol. This also applies to periods when therapy is not being carried out.
Application features
With parenteral administration of thioctic acid, hypersensitivity reactions up to anaphylactic shock have been observed. Therefore, patients should be under appropriate supervision. In the event of early symptoms (e.g. itching, nausea, weakness, etc.), treatment should be discontinued immediately; in certain circumstances, further therapeutic measures may be necessary.
Cases of autoimmune insulin syndrome (AIS) have been reported during treatment with thioctic acid. Patients with the human leukocyte antigen genotype (HLA-DRB1*04:06 and HLA-DRB1*04:03 alleles) are more prone to developing AIS during treatment with thioctic acid. The HLA-DRB1*04:03 allele (susceptibility factor for AIS development – 1.6) is particularly common in representatives of the Caucasian race (in Southern Europe more than in Northern Europe), and the HLA-DRB1*04:06 allele (susceptibility factor for AIS development – 56.6) is particularly common in Japanese and Korean patients.
AIS should be considered in the differential diagnosis of spontaneous hypoglycemia in patients using thioctic acid.
The main factor in the effective treatment of diabetic polyneuropathy is optimal correction of the patient's blood sugar level. Patients with diabetes mellitus, especially at the beginning of treatment, require frequent monitoring of blood glucose levels. In some cases, it is necessary to adjust the doses of antidiabetic drugs to prevent hypoglycemia. During the treatment of polyneuropathy, due to regeneration processes, a short-term increase in sensitivity is possible, accompanied by paresthesia with a feeling of crawling.
Drinking alcohol may reduce the effectiveness of the drug, so it is recommended to refrain from drinking alcohol during treatment with the drug.
The drug is light-sensitive, so the vials should be removed from the packaging only immediately before use.
A certain limitation for intravenous administration of thioctic acid preparations is the patient's advanced age (over 75 years).
Use during pregnancy or breastfeeding
According to the general principles of pharmacotherapy, medicines during pregnancy and lactation can be used only after a careful assessment of the benefit/risk ratio.
Pregnant and breastfeeding women should only be treated with thioctic acid strictly according to the indications established by the doctor, although reproductive toxicity studies have not revealed any effect on fertility and early embryonic development. Embryotoxic properties were also not revealed in the studies.
There is no data on the penetration of thioctic acid into breast milk.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
During the period of use of the drug, caution must be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, as adverse reactions from the nervous system and organs of vision are possible.
The ability to influence the reaction speed when driving or working with other mechanisms
During the period of use of the drug, caution must be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, as adverse reactions from the nervous system and organs of vision are possible.
Method of administration and doses
Adults.
Doses
For intense paresthesias caused by diabetic polyneuropathy, intravenous administration of a concentrate for solution for infusion is recommended at a dose of 24 ml (1 ampoule of Berlition® 600 IU) per day, which corresponds to 600 mg of thioctic acid per day.
After dilution, the concentrate for infusion solution is administered intravenously for 2-4 weeks at the initial stage of treatment. The contents of 1 ampoule of Berlition® 600 IU are diluted in 250 ml of 0.9% sodium chloride solution and administered intravenously, the infusion duration should be at least 30 minutes. Due to the sensitivity of the active substance to light, the infusion solution is prepared immediately before administration and protected from light, for example, using aluminum foil. The prepared infusion solution can be stored for about 6 hours if protected from light.
For further therapy, oral forms of thioctic acid are used at a dose of 300–600 mg per day.
Pediatric population.
There is no data.
The basis of treatment for diabetic polyneuropathy is optimal correction of the patient's blood sugar level.
Children
Berlithion® 600 IU is not intended for the treatment of children and adolescents due to the lack of clinical experience.
Overdose
Overdose may cause nausea, vomiting and headache. In case of accidental use or taking doses of 10 to 40 g of thioctic acid during a suicide attempt in combination with alcohol, severe intoxication is observed, which can be fatal. The clinical picture of poisoning is initially manifested by psychomotor agitation or impaired consciousness, later attacks of generalized convulsions and the development of lactic acidosis are observed. In addition, the consequences of intoxication with high doses of thioctic acid may be hypoglycemia, shock, rhabdomyolysis, hemolysis, disseminated intravascular coagulation (DIC), bone marrow suppression and multiorgan failure.
Treatment. If significant intoxication with thioctic acid is suspected (e.g. > 80 mg/kg body weight in adults and > 50 mg/kg body weight in children), immediate hospitalization and measures in accordance with the general principles of poisoning treatment (e.g. induction of vomiting, gastric lavage, use of activated charcoal, etc.) are indicated. Treatment of generalized convulsive attacks, lactic acidosis and other consequences of intoxication that threaten the patient's life should be based on the principles of modern intensive care and be carried out symptomatically. To date, there is no data on the feasibility of using hemodialysis, hemoperfusion or hemofiltration methods as part of the forced removal of thioctic acid.
Adverse reactions.
Classification of the frequency of adverse reactions:
very common: ≥ 1/10;
common: ≥ 1/100 - < 1/10;
uncommon: ≥ 1/1000 - < 1/100;
rare: ≥ 1/10,000 – < 1/1,000;
very rare: < 1/10,000;
not known: frequency cannot be estimated from the available data.
From the side of the hematopoietic system.
In isolated cases, petechial hemorrhages in the mucous membranes/skin, hypocoagulation, and thrombophlebitis were observed.
Very rare: after intravenous administration of thioctic acid, hemorrhagic rash (purpura), impaired platelet function have been observed.
From the immune system.
Not known: autoimmune insulin syndrome (see section "Special warnings and precautions for use").
Skin allergic reactions may occur in the form of rash, urticaria, itching, eczema, as well as systemic reactions up to the development of shock.
From the central nervous system.
Very rare: changes or disturbances in taste, headache, hot flashes, increased sweating, dizziness, visual disturbances. After intravenous administration of thioctic acid, convulsions and double vision have been observed. In most cases, all of these manifestations resolve on their own.
Not known: loss of consciousness, seizures.
From the digestive tract.
In some cases, with rapid intravenous administration of the drug, nausea, vomiting, diarrhea, and abdominal pain were observed, which resolved on their own.
On the part of the hepatobiliary system.
Not known: cholestatic hepatitis.
Metabolic disorders.
Very rare: due to improved glucose absorption, blood sugar levels may decrease, which may cause symptoms similar to those of hypoglycemia, such as dizziness, increased sweating, headache, and visual disturbances.
From the cardiovascular system.
With rapid intravenous administration, pain in the heart area and tachycardia may occur, which resolve on their own.
General adverse reactions and injection site reactions.
Common: after rapid intravenous administration, increased intracranial pressure and difficulty breathing may occur, which resolve spontaneously.
Very rare: In isolated cases, injection site reactions and weakness have been reported.
Reporting possible adverse reactions.
Reporting of suspected adverse reactions after the registration of a medicinal product plays an important role. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Expiration date
3 years.
Do not use the drug after the expiration date indicated on the package.
The shelf life after dilution with saline and provided protection from light is approximately 6 hours.
Storage conditions
Store ampoules in a cardboard box to protect from light.
Thioctic acid interacts in vitro with metal ion complexes (e.g. cisplatin).
Thioctic acid forms poorly soluble complex compounds with sugar molecules (for example, with fructose solution).
Berlithion® 600 U is incompatible with glucose solutions, Ringer's solution, as well as with solutions that react with SH groups or disulfide bridges.
For the use of the drug Berlithion® 600 U in the form of infusion, only physiological sodium chloride solution is used as a carrier solution.
Packaging
Brown glass ampoule containing 24 ml of concentrate for solution for infusion; 5 ampoules in a blister pack; 1 or 2 blister packs in a cardboard box.
Side effects
Classification of the frequency of adverse reactions:
very common: ≥ 1/10;
common: ≥ 1/100 - < 1/10;
uncommon: ≥ 1/1000 - < 1/100;
rare: ≥ 1/10,000 – < 1/1,000;
very rare: < 1/10,000;
not known: frequency cannot be estimated from the available data.
On the part of the hematopoietic system.
In isolated cases, petechial hemorrhages in the mucous membranes/skin, hypocoagulation, and thrombophlebitis were observed.
Very rare: after intravenous administration of thioctic acid, hemorrhagic rash (purpura), impaired platelet function have been observed.
From the immune system.
Not known: autoimmune insulin syndrome (see section "Special warnings and precautions for use").
Skin allergic reactions may occur in the form of rash, urticaria, itching, eczema, as well as systemic reactions up to the development of shock.
From the central nervous system.
Very rare: changes or disturbances in taste, headache, hot flashes, increased sweating, dizziness, visual disturbances. After intravenous administration of thioctic acid, convulsions and double vision have been observed. In most cases, all of these manifestations resolve on their own.
Not known: loss of consciousness, seizures.
From the digestive tract.
In some cases, with rapid intravenous administration of the drug, nausea, vomiting, diarrhea, and abdominal pain were observed, which resolved on their own.
On the part of the hepatobiliary system.
Not known: cholestatic hepatitis.
Metabolic disorders.
Very rare: due to improved glucose absorption, blood sugar levels may decrease, which may cause symptoms similar to those of hypoglycemia, such as dizziness, increased sweating, headache, and visual disturbances.
From the cardiovascular system.
With rapid intravenous administration, pain in the heart area and tachycardia may occur, which resolve on their own.
General adverse reactions and injection site reactions.
Common: after rapid intravenous administration, increased intracranial pressure and difficulty breathing may occur, which resolve spontaneously.
Very rare: In isolated cases, injection site reactions and weakness have been reported.
Reporting possible adverse reactions.
Reporting of suspected adverse reactions after the registration of a medicinal product plays an important role. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Vacation category
According to the recipe.
Producer
BERLIN-CHEMI AG.
Location of the manufacturer and address of its place of business.
Glienicker Weg 125, 12489 Berlin, Germany.
Address
Glienicker Weg 125, 12489 Berlin, Germany.
