HR 600 TIOKTATSID table. 30 table

Qualitative and quantitative composition

1 tablet contains 600 mq tioctic acid as an active ingredient.

 Formulation

Coated tablet

Clinical Data

  Witness

Treatment of the symptoms of peripheral (sensorimotor) diabetic polyneuropathy.

  Dosage and method of administration

Take 1 tablet Tioktatsid ® 600HR (equivalent to 600 mg tioctic acid) daily as a single dose, approximately half an hour before the first meal. When pronounced symptoms of peripheral (sensorimotor) diabetic polyneuropathy recommended The initial parenteral therapy.

Tablets Tioktatsid ® 600 HR should be swallowed whole with some liquid on an empty stomach.

Concomitant intake of food can lead to reduced absorption of thioctic acid. It is therefore recommended total daily dose be taken all at once before breakfast, especially in patients with prolonged gastric passage.

  Contraindications

Hypersensitivity to thioctic acid or to any of the excipients.

Note:

Tioktatsid HR 600  has not been studied in children and adolescents and therefore no clinical experience because of the medicinal product must not be used in patients in these age groups. Use during pregnancy and lactation

 Special warnings and special precautions for use

Regular alcohol consumption is a significant risk factor for the occurrence and progression of neuropathic clinical picture and may reduce the success of treatment with Tioktatsid. Therefore, patients with diabetic polyneuropathy should as far as possible, refrain from alcohol consumption. This goes for treatment free interval.

  Interactions

Concurrent use with Tioktatsid  600 HR can be weakened action of cisplatin. Tioktatsid is a metal chelator. Therefore the main reasons it should not be taken with metal compounds (eg products of iron, magnesium, milk products because they contained calcium). If Tioktatsid ® 600 HR taken 30 minutes before breakfast products of iron and magnesium can be taken only at lunch or dinner.

As can be increased hypoglycaemic effect of insulin and oral antidiabetic agents, recommended regular monitoring of blood glucose, especially at the beginning of therapy Tioktatsid ® 600HR. In isolated cases it may be necessary to reduce the dose of insulin or oral antidiabetic agents to avoid deficiency diabetes (hypoglycemia).

Pregnancy and lactation

The fundamental principles of drug therapy medicinal product should be administered to pregnant and lactating women after a rigorous assessment of the benefit / risk ratio. Pregnant and lactating women should be treated with thioctic acid in urgent indications, and only with a prescription. From previously published results for reproductive toxicity no data to influence fertility or early embryonic development. There is no evidence of embryotoxic effects.

So far, no evidence of drug transfer into breast milk.

 Effects on ability to drive and use machines

No

 Adverse reactions

In isolated cases have been reported occurrence of gastrointestinal symptoms such as. nausea, vomiting, abdominal pain, and diarrhea.

In isolated cases of allergic reactions resulting in skin rash, hives and itching

ased on the improved glucose tolerance in some cases may be a drop in blood sugar. In these cases described symptoms similar to those of hypoglycemia, such as dizziness, sweating, headache and visual disturbances.

 Overdose

After unintentional oral intake or suicidal doses of 10 to 40d thioctic acid in combination with alcohol are described cases of severe poisoning is sometimes fatal. Clinical signs of toxicity occur initially in psychomotor agitation or clouding of consciousness, the further course was accompanied by typical events such as generalized seizures, and lactic acidosis. As a consequence of intoxication with high doses of thioctic acid are described and hypoglycemia, shock, rhabdomyolysis, hemolysis, disseminated intravascular coagulation (DIC), bone marrow suppression and multiple organ failure.

Therapeutic measures for intoxication:

Even the slightest suspicion of intoxication Tioktatsid (eg> 10 tablets of 600mg for adults and> 50 mg / kg body weight in children) require immediate hospitalization and taking general therapeutic measures in case of intoxication (eg induction vomiting, gastric lavage, administration of activated charcoal, etc.).. Treatment of generalized seizures, lactic acidosis and other life-threatening consequences of intoxication must be in accordance with the principles of modern intensive therapy and symptomatic. The need for hemodialysis and haemoperfusion techniques and filter in a forced elimination of thioctic acid has not yet been confirmed.

 Pharmacological

 Pharmacodynamic properties

Through challenges and jug of diabetes hyperglycaemia leads to accumulation of glucose in the protein matrix of blood vessels and the formation of so-called "Advanced Glycosylation End Products". This process leads to reduced blood flow endonevralniya and endonevralna hypoxia / ischemia, which is associated with increased production of oxygen free radicals that damage peripheral nerves. Moreover, peripheral nerves settled depletion of antioxidants, such as. glutathione.

In clinical trials in rats found that thioctic acid involved in these biochemical processes that cause increased blood flow endonevralniya streptozototsin-induced diabetes, which leads to increased physiological levels of the antioxidant glutathione as well as antioxidant reduces free oxygen radicals the nerve vessels in diabetics. These effects observed in experimental situations show that the function of peripheral nerves can be significantly improved by thioctic acid. This applies to sensory disorders in diabetic neuropathy, which can occur as dysesthesia, paresthesia, eg. burning, pain, a feeling of deafness, numbness.

In the experimental situation thioctic acid activates nerve and muscle and fat cells, similar to insulin, glucose uptake through phosphatidylinositol kinase-H.

Pharmacokinetics

After oral administration in humans thioctic acid is rapidly absorbed. Due to rapid tissue distribution the half-life of thioctic acid in humans is about 25 minutes. Maximum plasma level of about 4mg/ml measured after about half an hour after oral administration of 600 mg of thioctic acid. By radiolabelling, in animal experiments (rats, dogs) is shown mainly by the kidneys, and excretion (80-90%) as metabolites. Also in humans in urine were found trace amounts eliminated intact substance. Biotransformation takes place mostly through oxidative (p-oxidation) shorter side chains and / or S-methylation of the corresponding thiols.

Bioavailability

Following the marked first-pass-effect absolute bioavailability (compared to iv application) of thioctic acid (defined as basic substance) in Tioktatsid HR 600 tablets is about 20%. Like oral solution, which is standard for maximum absorption Tioktatsid HR 600 shows absorption profile, with rapid penetration of the drug, combined with reduced individual variability. The relative bioavailability of Tioktatsid  600 HR (compared to oral solution) is> 60%.

 Preclinical safety data

Acute and chronic toxicity

Toxicity profile is characterized by symptoms that affect equally the autonomic and central nervous system (see section 4.9. "Overdose"). After repeated application is found to be target organs are the liver and kidneys.

Mutagenic and tumorigenic potential

Studies on the mutagenic potential revealed no evidence of gene and chromosome mutations.

Clinical trials with rat oral carcinogenicity show no evidence of tumorigenic potential of thioctic acid. Clinical studies for tumor-provoking effect of thioctic acid in relation to carcinogen N-nitrozodimetilamin (NDEA) gave negative results.

Reproductive Toxicity list taken from desk

For maximum oral doses up to 68,1 mg / kg thioctic acid had no effect on fertility or on early embryonic development in rats.

Intravenous doses toxic to the mother rabbit did not occur malformations.

 Pharmaceutical Data

 List of excipients and their amounts

Low-substituted hydroxypropy! cellulose (L-HPC LH-22) 157,00 mg

Hydroxypropylcellulose (Klucel EF) 20,00 mg

Magnesium stearate 24,00 mg

Hydromelose (Hydroxypropylmethylcellulose) 15,80 mg

Methylhydroxypropylcellulose 14,58 m

4,70 mg Macrogol 600 

Titanium dioxide (E 171) 4,00 mg

Talc 2,02 mg 

Aluminium hydroxide lacquero of Quinoline yellow (E 104) 1,32 mg 

Aluminium hydroxide lacquero of Indigo carmine (E 132) 0,16 m 

 Fiziko-Incompatibilities

Currently there is no known.

  Expiration date

3 years

 Special precautions for storage

Do not store above +30 ° C (86 ° F)! Keep out of reach of children!