Thiolipon® film-coated tablet 300 mg or 600 mg

Thiolipon® film-coated tablet 300 mg or 600 mg

International nonproprietary name

Thioctic acid

Pharmacological group

Метаболические средства

Composition

 

Thioctic acid (lipoic acid)                                          - 300 mg         - 600 mg

Excipients of the core:
silicium dioxide colloidal (aerosil)                             - 7.5 mg          - 12.3 mg
microcrystalline cellulose                                         - 50 mg           -41 mg
hypromellose (oxypropylmethylcellulose)                - 5 mg             - 8.2 mg
carboxymethyl starch (primogel)                             - 17.5 mg         - 28.7 mg
calcium stearate                                                       - 5 mg             - 8.2 mg
calcium stearate monohydrate                                 - 5 mg             - 8.2 mg
sodium chloride                                                        - 5 mg             - 8.2 mg                     
magnesium hydroxide (talc)                                     - 13.5 mg        - 24.6 mg
lactose monohydrate (lactobiose)                             - 91.5 mg        - 80.6 mg
Excipients of the coating:
Opadry II including:                                                   - 10 mg           - 12 mg
hypromellose (oxypropylmethylcellulose)                 - 3.4 mg          - 4.1 mg
lactose monohydrate (lactobiose)                             - 3.0 mg          - 3.6 mg
macrogol 4000 (polyethylene oxide 4000)               - 1.1 mg          - 1.3 mg
Staining pigments:                                                     - 2.5 mg          - 3.0 mg
titanium dioxide, Е 171                                              - 2.0 mg          - 2.4 mg
quinoline yellow aluminium lake, Е 104                    - 0.40 mg        - 0.48 mg
sunset yellow aluminium lake, Е 132                        - 0.05 mg        - 0.06 mg
indigo carmine aluminium lake, Е 132                      - 0.05 mg        - 0.06 mg
Weight of a tablet                                                      - 510 mg         - 832 mg

 

Pharmacological action

Thioctic acid (alpha lipoic acid) is an endogenous antioxidant (binding free radicals), it forms in the body during oxidative decarboxylation of alpha-keto acids. The drug as a coenzyme of mitochondrial multienzyme complexes is involved in oxidative decarboxylation of pyruvic acid and alpha-keto acids. The drug promotes reducing blood glucose and glycogen in the liver, as well as eliminates insulin resistance. The nature of biochemical effect is close to the vitamins of group B.
It participates in regulation of lipid and carbohydrate metabolism, stimulates exchange of cholesterol. Thioliponhas hepatoprotective, hypolipidemic, hypocholesterolemic, hypoglycemic effects. Thiolipon improves trophic neurons. In patients with diabetes mellitus thioctic acid reduces formation of final glycation products, improves endoneural blood flow, increases glutathione content up to a physiological value, which results in improvement of functional state of peripheral nerve fibers associated with diabetic polyneuropathy. Due to participation in fat metabolism thioctic acid increases biosynthesis of phospholipids, in particular phosphoinositides, restoring cell membrane damage; normalizes the energy balance and conductivity of nerve impulses.
Thioctic acid eliminates the toxic effect of alcohol metabolites (acetaldehyde, pyruvic acid), reduces excess formation of molecules of free oxygen radicals, reduces endoneural hypoxia and ischemia, relieving symptoms of polyneuropathy in the form of paresthesias, burning sensations, pain and limb numbness. Thus, thioctic acid has an antioxidant, neurotrophic effect, improves lipid metabolism.

Pharmacokinetics

Absorption
After oral administration the drug is quickly and completely absorbed from the gastrointestinal tract (administration with food reduces absorption). Time to the maximum concentration is 40 - 60 minutes. Bioavailability is 30 %.
Distribution
The volume of distribution is about 450 ml / kg. Total plasma clearance is 10 - 15 l/min.
Metabolism
Thioctic acid has the effect of first pass through the liver. Metabolite formation occurs as a result of the side chainoxidation and conjugation. Recovery
Thioctic acid and its metabolites are excreted by the kidneys (8090 %). Half-life is 20 - 50 minutes.

Indications for Use

Diabetic polyneuropathy and alcoholic polyneuropathy.

Contraindications

Increased sensation to the drug components;
Pregnancy, lactation period (lack of adequate experience of the drug administration).
Pediatric use at the age less than 18 years old (safety and efficacy are not determined); Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
Administration during pregnancy and lactation period
Administration of thioctic acid during pregnancy is contraindicated due to the lack of sufficient experience of its use. Data on penetration of tioctic acid into the breast milk is not available, therefore breastfeeding should be discontinued if the drug is required during the lactation period.

Cautions

Patients with diabetes mellitus require frequent monitoring of glucose concentration in the blood especially at the beginning of treatment, . In some cases dose of hypoglycemic agents shall be reduced to prevent hypoglycemia.
Administration of thioctic acid requires avoiding to drink alcohol during the treatment period and, if possible, within the intervals between courses, because ethanol reduces the therapeutic effectiveness of thiectic acid.
During the treatment of thioctic acid, cases of autoimmune insulin syndrome (AIS) have been reported. Patients with the genotype of the human leukocyte antigen (HLA-DRB1 * 04: 06 and HLA-DRB1 * 04: 03 alleles) are more susceptible to development of AIS during the treatment with thioctic acid. Allele HLA-DRB1 * 04: 03 (the risk of AIS is 1.6 times higher) is mainly found in Europeans, more often in Southern Europe than in the North, and the HLA-DRB1 * 04: 06 allele (the risk of AIS is 56 , 6 times higher) is more common in Japanese and Koreans.
The possible AIS in the differential diagnosis of spontaneous hypoglycemia in patients receiving tioctic acid shall be considered.
Effects on ability to drive and use machines
During the treament avoid driving and performing other potential hazardous activities requiring increased attention focusing and quick psychomotor reactions.

Dosing and Administration

Tablets are administered orally on an empty stomach, approximately 30 minutes before the first meal, without chewing and with sufficient amount of water.
For diabetic polyneuropathy and alcoholic polyneuropathy, the drug is administered at dose 600 mg once per day.
For severe diabetic polyneuropathy the treatment should preferably start with parenteral administration of thioctic acid within 2 to 4 weeks.
Then the treatment should be continued with oral administration of the drug at dose 600 mg once per day. The minimum duration of the therapy is 3 months. In some cases, the treatment with the drug can last for longer time, the exact duration shall be determined by a doctor.

Side effect

 

The frequency of adverse effects is indicated in accordance with the classification of the World Health Organization:

- very common (≥ 1/10),
- common (frequent)(≥ 100, < 1/10),
- uncommon (infrequent) (≥ 1/1000, < 1/100),
- rare (≥ 1/10000, < 1/1000),
- very rare (≥ 1/10000),
- unknown frequency - data on the the adverse reaction frequency is not available.
Adverse immune system effects:
very rare - allergic reactions, including urticaria (urticaria rash), skin rash, itching; in individual cases - systemic allergic reactions (up to development of anaphylactic shock);
unknown frequency - autoimmune insulin syndrome.
Adverse metabolism and digestive  effects:
very rare - decreased concentration of glucose in the blood (due to improved absorption of glucose). Complaints certifying hypoglycemic condition, namely: dizziness, increased sweating, headache, impaired vision were reported sometimes.
Adverse nervous system effects:
very rare - change or disorders of taste.
Adverse gastrointestinal effects:
very rare- nausea, heartburn, vomiting, abdominal pain and gastrointestinal pain, diarrhea.
Other:
unknown frequency - eczema.
Overdose
Symptoms: headache, nausea, vomiting.
Administration of very high doses of thioctic acid from 10 to 40 g, especially in combination with alcohol causes severe intoxication, which can lead to death.
In severe cases (administration of more than 10 tablets ad tose 600 mg or more, 20 tablets at dose 300 mg by adults or dose more than 50 mg/kg of the body weight in children): psychomotor agitation, consciousness disturbance, generalized convulsions, lactic acidosis, hypoglycemia (up to coma ), acute necrosis of skeletal muscles, hemolysis, disseminated intravascular coagulation, bone marrow dysfunction and multiple organ failure.
Treatment: no specific antidote.
In case of suspected severe intoxication, immediate admission and measures in accordance with the general principles adopted for accidental poisoning (for example, vomiting, stomach lavage, activated charcoal) are recommended.
Symptomatic treatment for generalized convulsions, lactic acidosis and other consequences of intoxication, life-threatening, should be conducted in accordance by the advanced intensive care methods. To date, efficacy of hemodialysis, hemoperfusion and filtration methods with forced excretion of thioctic acid has not been confirmed.

 

Interaction with other medicines

Simultaneous administration of thioctic acid and cisplatin decreases efficacy of cisplatin. Thioctic acid binds metals, therefore it should not be administered simultaneously with preparations containing metals (such as iron, magnesium, calcium), as well as dairy products (due to calcium content in them); the interval between administration of such drugs and thioctic acid should be at least 2 hours.
Simultaneous administration of thiectic acid and insulin or oral hypoglycemic agents enhances their effect. The drug enhances the anti-inflammatory effect of glucocorticosteroids.
Ethanol and its metabolites reduce the effect of thioctic acid.

Form release

Storage conditions

In a dark place at temperature maximum 25 °С.

Expiration date

3 years