Geptral

General characteristics. Structure:

The bottle with lyophilisate contains:

Active agent: an ademetionina of 1,4-butandisulfonat 760 mg (there correspond 400 mg of an ion of an ademetionin).

The ampoule with solvent contains:

Excipients: L-lysine of 342,4 mg; sodium hydroxide of 11,5 mg; water for injections to 5 ml.

Description

Lyophilisate

From color, almost white to white with a yellowish shade, lyophilisate without foreign inclusions.

Solvent

Transparent liquid from colourless till light-yellowish color without foreign inclusions.

The recovered solution

Transparent solution from colourless till yellow color without visible deposit.

Pharmacological properties:

Pharmacodynamics. Ademetionin treats group of gepatoprotektor, has also antidepressive activity. Has holeretichesky and holekinetichesky effect, has the detoksikatsionny, regenerating, antioxidant, antifibroziruyushchy and neuroprotective properties.

Fills shortage of S-аденозил-L-methionine (ademetionin) and stimulates its development in an organism, contains in all environments of an organism. The greatest concentration of an ademetionin is noted in a liver and a brain. Carries out a key role in metabolic processes of an organism, takes part in important biochemical reactions: transmethylation, transsulphonating, transamination. In transmethylation reactions адеметионин tints methyl group for synthesis of phospholipids of cellular membranes, neurotransmitters, nucleic acids, proteins, hormones, etc. In reactions of transsulphation of an ademetionin is a predecessor of cysteine, taurine, glutathione (providing the oxidation-reduction mechanism of a cellular detoxication), acetylation coenzyme (joins in biochemical reactions of a cycle of tricarboxylic acids and fills energy potential of a cell). Increases the maintenance of a glutamine in a liver, cysteine and taurine in plasma; reduces the content of methionine in serum, normalizing metabolic reactions in a liver. After decarboxylation participates in aminopro-milling reactions as the predecessor of polyamines — a putrestsin (a stimulator of cell regeneration and proliferation of hepatocytes), the spermidine and spermine entering into structure of ribosomes that reduces risk of fibrosing. Has holeretichesky effect. Ademetionin normalizes synthesis of endogenous phosphatidylsincaline in hepatocytes that increases the flowability and polarization of membranes. It improves function of the hepatocytes of transport systems of bile acids associated with membranes and promotes a passage of bile acids in bile-excreting system. It is effective at intra hepatic (intra lobular and interlobular) cholestasia option (disturbance of synthesis and current of bile). Ademetionin reduces toxicity of bile acids in a hepatocyte, carrying out their konjyugirovaniye and sulphation. Conjugation with taurine increases solubility of bile acids and their removal from a hepatocyte. Process of sulphation of bile acids promotes a possibility of their elimination by kidneys, facilitates passing through a membrane of a hepatocyte and removal with bile. Besides, the sulphated bile acids in addition protect membranes of cells of a liver from toxic effect of not sulphated bile acids (in high concentration of attendees in hepatocytes at an intra hepatic cholestasia). At patients with diffusion diseases of a liver (cirrhosis, hepatitis) with a syndrome of an intra hepatic cholestasia адеметионин reduces expressiveness of a skin itch and changes of biochemical indicators, including level of direct bilirubin, activity of an alkaline phosphatase, aminotransferases, etc. the Holeretichesky and gepatoprotektivny effect remains up to 3 months after the treatment termination. Efficiency at the hepatopathies caused by various hepatotoxic drugs is shown. Appointment to patients with the opioid drug addiction which is followed by damage of a liver leads to regression of clinical manifestations of abstinence, improvement of a functional condition of a liver and processes of a microsomal oxidation. Antidepressive activity is shown gradually, since the end of the first week of treatment and is stabilized within 2 weeks of treatment. It is effective at recurrent endogenous and neurotic depressions, resistant to amitriptyline. Has ability to interrupt a depression recurrence. Appointment at osteoarthrites reduces expressiveness of a pain syndrome, increases synthesis of proteoglycans and leads to partial regeneration of cartilaginous tissue.

Pharmacokinetics. Bioavailability at parenteral administration — 96%, concentration in plasma reaches the maximum values in 45 minutes. It is metabolized in a liver. Communication with proteins of a blood plasma — insignificant. Gets through a blood-brain barrier. Significant increase in concentration of an ademetionin in cerebrospinal fluid is noted.

Time of semi-removal (T1/2) — 1.5 h. It is removed by kidneys.

Indications to use:

Intra hepatic cholestasia at pretsirrotichesky and cirrhotic states which can be observed at the following diseases:
- fatty dystrophy of a liver;
- chronic hepatitis;
- toxic damages of a liver of various etiology, including alcoholic, virus, medicinal (antibiotics; antineoplastic, antitubercular and antiviral drugs, tricyclic antidepressants, oral contraceptives);
- chronic acalculous cholecystitis;
- cholangitis;
- cirrhosis;
- encephalopathy, including associated with a liver failure (alcoholic, etc.).
- An intra hepatic cholestasia at pregnant women.
- Depression symptoms.

Route of administration and doses:

Intravenously and intramusculary.

Lyophilisate needs to be dissolved in specially enclosed solvent just before introduction. The rest of drug has to be utilized.

Drug cannot be mixed with the alkaline solutions and solutions containing calcium ions.

The drug Geptral® at intravenous use is administered very slowly.

Intra hepatic cholestasia

From 400 mg/days to 800 mg/days (1 — 2 bottle a day) within 2 weeks.

Depression

From 400 mg/days to 800 mg/days (1 — 2 bottle a day) within 15 — 20 days.

In need of a maintenance therapy it is recommended to continue administration of drug of Geptral® in the form of tablets in a dose of 800 — 1600 mg/days for 2 — 4 weeks.

Features of use:

Considering tonic effect of drug, it is not recommended to accept it before going to bed. At purpose of the drug Geptral® systematic control of level of nitrogen in blood is necessary for patients with cirrhosis against the background of a hyperazotemia. During long therapy it is necessary to determine the content of urea and creatinine in blood serum.

It is not recommended to appoint адеметионин to patients with bipolar disorders. The patients accepting адеметионин have messages on transition of a depression to a hypomania or mania.

Also the patients accepting адеметионин have messages on sudden emergence or increase of concern. In most cases cancellation of therapy is not required, in several cases the concern was resolved after a dose decline or drug withdrawal.

As deficit of cyanocobalamine and folic acid can reduce the level of an ademetionin at patients of risk group (with anemia, liver diseases, at pregnancy or probability of a vitamin deficiency, in connection with other diseases or a diet, for example, at vegetarians), it is necessary to control the level of vitamins. If insufficiency is found, the concomitant use of an ademetionin with cyanocobalamine and folic acid is recommended.

At immunoassay use of an ademetionin can promote false definition of an indicator of high level of a gomotsistein in blood.

For the patients accepting адеметионин it is recommended to use not immunological methods of the analysis for determination of level of a gomotsistein.

Influence on ability to drive the car and to work with mechanisms

Some patients at administration of drug of Geptral® can have a dizziness. It is not recommended to drive the car and to work with mechanisms during administration of drug until patients are not sure that therapy does not influence ability to be engaged a similar look in activity.

Side effects:

Among the most frequent side reactions are noted: nausea, abdominal pain and diarrhea. The generalized data on side reactions which were noted against the background of use of an ademetionin both in tablets, and in an injection dosage form are included below.

From immune system: throat hypostasis, allergic reactions.

From skin: reactions in an injection site (it is very rare with a skin necrosis), perspiration, an itch, rash, a Quincke's edema, skin reactions.

Infections and invasions: infections of urinary tract.

From a nervous system: dizziness, headache, paresthesias, concern, confusion of consciousness, sleeplessness.

From cardiovascular system: inflows, phlebitis of superficial veins, cardiovascular disturbances.

From system of digestion: abdominal distention, an abdominal pain, diarrhea, dryness in a mouth, dyspepsia, an esophagitis, a meteorism, gastrointestinal frustration, gastrointestinal bleeding, nausea, vomiting, hepatic colic, cirrhosis.

From a musculoskeletal system: arthralgia, muscular spasms.

Another: adynamy, fever, grippopodobny syndrome, indisposition, peripheral hypostases, fever.

Interaction with other medicines:

The known interactions with other medicines were not observed.

The patient accepting адеметионин and кломипрамин has a message on a syndrome of excess of serotonin. It is considered that such interaction is possible and it is necessary to appoint with care адеметионин together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as кломипрамин), and also the herbs and drugs containing tryptophane.

Contraindications:

The genetic disorders influencing a metioninovy cycle, and/or a defiant homocystinuria and/or a gipergomotsisteinemiya (deficit цистатионин beta synthases, cyanocobalamine metabolism disturbance);

Hypersensitivity to any of drug components;

Age up to 18 years (experience of a medical use at children is limited).

With care

Bipolar disorders (see the section "Special Instructions").

Pregnancy (I trimester).

Feeding period breast.

Use at pregnancy and during breastfeeding

Use of high doses of an ademetionin in the III trimester of pregnancy did not cause any undesirable effects. Use of the drug Geptral® for pregnant women in the I trimester and during breastfeeding is possible, only if the potential advantage for mother exceeds possible risk for a fruit or the child.

Overdose:

Clinical cases of overdose were not noted.

Storage conditions:

In the place protected from light at a temperature from 15 °C to 25 °C. To store in the place, unavailable to children. Period of validity 3 years. Not to use drug after a period of validity.

Issue conditions:

According to the recipe

Packaging:

760 mg of lyophilisate in the bottle from colourless glass like I corked by a chlorbutyl stopper with an aluminum cap with a plastic cover.

Solvent on 5 ml in ampoules from glass like I with a point break.

On 5 bottles and 5 ampoules in a cardboard pack together with the instruction on a medical use.

On 5 bottles and 5 ampoules in the plastic blister strip packaging covered with aluminum foil. On 1 blister strip packaging in a cardboard pack together with the instruction on a medical use.