Instructions for Espa-Lipon 600 film-coated tablets 600 mg No. 30
Composition
active ingredient: thioctic acid;
1 tablet contains 600 mg of thioctic acid;
excipients: lactose monohydrate, povidone, microcrystalline cellulose, powdered cellulose, highly dispersed silicon dioxide, precipitated silicon dioxide, sodium starch glycolate (type A), magnesium stearate, hypromellose, macrogol 6000, talc, titanium dioxide (E 171), quinoline yellow (E 104).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, oblong in shape, yellow in color with a break notch.
Pharmacotherapeutic group
Drugs that affect the digestive system and metabolic processes. Thioctic acid.
ATX code A16A X01.
Pharmacological properties
Pharmacodynamics.
Thioctic acid is a 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, associated with increased formation of free oxygen radicals that damage the nerve, as well as to the depletion of such an antioxidant as glutathione in peripheral nerves. In 1995, a multicenter placebo-controlled study was conducted to study the effectiveness of using thioctic acid for the symptomatic treatment of diabetic polyneuropathy, which obtained data on the beneficial effects of thioctic acid on such studied symptoms as paresthesia, burning sensation, numbness and pain.
Pharmacokinetics.
Thioctic acid has a high first-pass effect in the liver. There are significant interindividual differences in the systemic availability of thioctic acid. Biotransformation of thioctic acid occurs by oxidation of side chains and fusion. Excretion is mainly renal.
In humans, the plasma half-life is about 25 minutes, the total plasma clearance is 10–15 ml/min/kg. At the end of a 30-minute infusion of 600 mg, the determined plasma level is about 20 μg/ml. Radiolabeling in animal studies (rats, dogs) has shown that 80–90% of the drug is excreted predominantly as metabolites. In humans, only a small amount of unchanged substance is excreted in the urine. Biotransformation occurs mainly by oxidative reduction of side chains (beta-oxidation) and/or S-methylation of thiol groups.
Indication
Symptomatic treatment of diabetic polyneuropathy.
Contraindication
Hypersensitivity to thioctic acid or to one of the other components of the drug.
Interaction with other medicinal products and other types of interactions
The effectiveness of cisplatin is reduced when used simultaneously with the drug. Thioctic acid is a metal complexing agent and therefore, according to the basic principles of pharmacotherapy, it should not be used simultaneously with metal compounds (for example, with food supplements containing iron or magnesium, with dairy products, since they contain calcium). If the total daily dose of the drug is taken 30 minutes before breakfast, then food supplements containing iron and magnesium should be taken in the middle of the day or in the evening. When using thioctic acid in patients with diabetes mellitus, it is possible to enhance the blood sugar-lowering effect of insulin and oral antidiabetic agents, therefore, especially at the initial stage of treatment, careful monitoring of blood sugar levels is recommended. To avoid symptoms of hypoglycemia, in some cases, a reduction in the dose of insulin or oral antidiabetic agents may be required.
Application features
The main factor in the effective treatment of diabetic polyneuropathy is optimal correction of the patient's blood sugar level. At the beginning of treatment for polyneuropathy, a short-term increase in paresthesias with a feeling of "crawling ants" is possible due to regeneration processes. When using thioctic acid, patients with diabetes mellitus require frequent monitoring of blood glucose levels. In some cases, it is necessary to reduce the doses of antidiabetic drugs to prevent the development of hypoglycemia. Regular consumption of alcoholic beverages is a significant risk factor for the development and progression of polyneuropathy and may hinder the success of treatment, therefore, during treatment and in the periods between courses of treatment, alcohol should be avoided.
One case of autoimmune insulin syndrome (AIS) has been reported during treatment with thioctic acid. Patients with certain HLA (human leukocyte antigen) genotypes, such as the HLA-DRB1*04:06 and HLA-DRB1*04:03 alleles, are more likely to develop AIS during treatment with thioctic acid. The HLA-DRB1*04:03 allele (odds ratio for AIS 1.6) is predominantly found in Caucasians, with a higher prevalence in Southern Europe than in Northern Europe. The HLA-DRB1*04:06 allele (odds ratio for AIS 56.6) is predominantly found in Japanese and Korean patients. The possibility of developing AIS in patients using thioctic acid should be taken into account in the differential diagnosis of spontaneous hypoglycemia (see section "Adverse reactions").
Use during pregnancy or breastfeeding
Fertility.
A reproductive toxicity study revealed no evidence of an effect on fertility.
Pregnancy.
Espa-lipon® 600 can be used during pregnancy only after a careful assessment of the benefit/risk ratio.
Lactation.
There is no data on the penetration of thioctic acid or its metabolites into breast milk. A decision should be made whether to discontinue breastfeeding or discontinue the drug Espa-lipon® 600 taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Method of administration and doses
Adults.
Doses
The daily dose is 1 tablet of Espa-lipon® 600 (equivalent to 600 mg of thioctic acid), which should be taken once approximately 30 minutes before the first meal. In case of intense paresthesias, infusion therapy with thioctic acid can be started.
Method of application
Espa-lipon® 600 tablets should be taken on an empty stomach, swallowed whole and with sufficient liquid. Simultaneous food intake may hinder absorption, so in patients with slow gastric emptying, it is especially important that the drug is taken half an hour before breakfast. Since diabetic polyneuropathy is a chronic disease, long-term therapy may be necessary. The basis of treatment of diabetic polyneuropathy is optimal diabetic control.
Children
Since there are no data on the safety and efficacy of thioctic acid in children, the drug is not recommended for use in this age group of patients.
Overdose
Overdose may cause nausea, vomiting and headache. After accidental ingestion or attempted suicide with oral administration of thioctic acid in doses from 10 g to 40 g in combination with alcohol, significant intoxications, in some cases with a fatal outcome, have been observed. At the initial stage, the clinical picture of intoxication may manifest itself in psychomotor agitation or in clouding of consciousness. Generalized convulsions and lactic acidosis then occur. In addition, hypoglycemia, shock, acute skeletal muscle necrosis, hemolysis, disseminated intravascular coagulation syndrome, bone marrow suppression and multiple organ failure have been described in intoxication with high doses of thioctic acid.
Treatment. If severe intoxication is suspected, immediate hospitalization is recommended and measures are taken in accordance with the general principles of accidental poisoning (e.g., induction of vomiting, gastric lavage, administration of activated charcoal). Treatment of generalized convulsions, lactic acidosis and other life-threatening consequences of intoxication should be carried out in accordance with the principles of modern intensive care and should be symptomatic. The benefit of hemodialysis, hemoperfusion or filtration methods with forced removal of thioctic acid has not yet been confirmed.
Side effects
The following classification was used to assess the frequency of adverse events:
very common: ≥ 1/10;
common: ≥ 1/100 – < 1/10;
uncommon: ≥ 1/1000 – < 1/100;
rare: ³ 1/10000 – < 1/1000;
very rare: < 1/10,000;
unknown: cannot be estimated from the available data.
Immune system disorders.
Very rare: allergic reactions, including skin rashes, hives (urticaria), itching, difficulty breathing.
Not known: autoimmune insulin syndrome (see section "Special warnings and precautions for use"), eczema.
Metabolic and nutritional disorders.
Very rare: hypoglycemia.
Nervous system disorders.
Common: dizziness.
Very rare: dysgeusia, headache, hyperhidrosis.
Visual impairment.
Very rare: visual disturbances.
Digestive tract disorders.
Common: nausea.
Very rare: vomiting, gastrointestinal pain, diarrhea.
General disorders.
Very rare: decreased blood glucose levels associated with improved glucose absorption. Symptoms similar to hypoglycemia: dizziness, sweating, headache and visual disturbances.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 film-coated tablets in a blister, 3 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Advance Pharma GmbH.
Location of the manufacturer and its business address
Wallenroder Str. 8-14, 13435 Berlin, Germany.
Applicant
Esparma GmbH, Germany.
Applicant's location
Bielefelder Strasse 1, 39171 Sulzetal, Germany.
