for medical use
of GEPTRAL medicine
A trade name
Mezhdunarodnoye the unlicensed
name Ademetionin Lekarstvennaya
the Tablet form, covered with a kishechnorastvorimy cover, 500 mg
One tablet contains
active agent – an ademetionin of 1.4-butandisulfonat 949 mg (500 mg of a cation of an ademetionin are equivalent),
excipients: silicon dioxide colloidal anhydrous, starch sodium glycollate, magnesium stearate, cellulose microcrystalline,
structure of a kishechnorastvorimy cover: ethyl acrylate methacrylic acid kopolimer, macrogoal 6000, polysorbate 80, simetikona emulsion, sodium hydroxide, talc.
of the Tablet of an oval form, with a biconvex surface, coated from white till yellowish color, without cracks, effect of a hat and swelling
Other drugs for treatment of gastrointestinal diseases and disbolism. Amino acids and their derivatives. Ademetionin.
The ATX A16A A02 code
Pharmacokinetics Absorption At properties of the person after intravenous administration a pharmacokinetic profile of an ademetionin is biexpotentsialny with a fast phase of distribution in fabrics and clearance with elimination half-life about 1.5 h. Absorption at intramuscular introduction of 96%, the maximum plasma concentration are reached in 45 min. after use. After intake of kishechnorastvorimy tablets of an ademetionin (400 1000 mg) the reached maximum plasma concentration are dose-dependent and make 0.5 1 mg/l in 3 5 hours. The bioavailability after oral administration increases if ademetionin it is applied between meals. Plasma concentration decrease to reference values within 24 hours.
the Volume of distribution makes 0.41 and 0.44 l/kg for doses of an ademetionin of 100 mg and 500 mg respectively. Linking with serum proteins insignificant also makes also le, 5%.
Process of metabolism of an ademetionin is cyclic and is called a cycle of an ademetionin. At the first stage of this cycle the ademetionin-dependent metilaza uses ademetionin as substrate for products S-adenozil-gomotsisteina which is hydrolyzed then to a gomotsistein and adenosine by means of S-adenozil-gomotsistein-gidralazy. Gomotsistein in turn is exposed to the return transformation to methionine by transfer of methyl group from 5 methyltetrahydrofolates. Finally, methionine can be transformed in ademetionin, finishing a cycle.
Approximately at 60% of the total number of the healthy volunteers participating in researches on intake of a radioactive (methyl 14C) ademetionin, renal excretion was 15.5±, 1.5% in 48 h, excretion with excrements 23.5±, 3.5% in 78 h.
Geptral (active agent – S-аденозил-L-methionine (ademetionin)) natural amino acid which is present at all fabrics and fluid mediums of an organism. Geptral (ademetionin) first of all acts as coenzyme and the donor of methyl group in many reactions of transmethylation. Transfer of methyl groups (transmethylation) of an ademetionin is a basis at creation of a phospholipidic cell membrane and plays a role in the fluidity of membranes.
Geptral (ademetionin) is capable to get through a blood-brain barrier. High concentrations of Geptral (ademetionin) influence the transmethylation processes which are very important in brain fabric thanks to influence on metabolism of catecholamines (dopamine, adrenaline, noradrenaline), indolamines (serotonin, melatonin) and a histamine.
Geptral (ademetionin) is also a predecessor of biochemical thiol connections (cysteine, taurine, glutathione, coenzyme A, etc.) in transsulphonating reactions.
Glutathione, the most powerful antioxidant, is an important component for a hepatic detoxication. Geptral increases glutathione level at patients with damage of a liver of both alcoholic, and not alcoholic genesis. Folic acid and B12 vitamin are essential to – nutrients in metabolism and Geptral’s (ademetionina) accumulation.
The intra hepatic cholestasia
Drug is effective at treatment of an intra hepatic cholestasia in liver diseases, during pregnancy and other chronic hepatic diseases.
The intra hepatic cholestasia is a complication of chronic diseases of a liver and is the reason of damage of hepatic cells.
In chronic diseases of a liver such functions of hepatocytes as clearance and regulation of production of bile acids are broken that leads ment of an intra hepatic cholestasia.
Use of an ademetionin was studied at patients with the chronic diseases of a liver which are often followed by a vnutripechechny cholestasia: primary biliary cirrhosis, primary sclerosing cholangitis, lekarstvenno – the induced damages of a liver, a viral hepatitis, the cholestasia induced by parenteral nutrition, damages of a liver of alcoholic and not alcoholic genesis.
Geptral (ademetionin) was applied parenterally and inside to treatment depressss. Antidepressive action was shown for 5-7 day of treatment in the absence of side effects, including anticholinergic reactions.
An intra hepatic cholestasia of pregnant women
Treatment ademetioniny (in/in, in oil, inside in the form of tablets) is effective at an intra hepatic cholestasia of pregnant women and is shown in the form of reduction of a skin itching and improvement of biochemical parameters.
– an intra hepatic cholestasia at pretsirrotichesky states and cirrhosis
– an intra hepatic cholestasia at pregnant women in the III trimester
– a depressive syndrome
the Route of administration and doses
Treatment can be begun with parenteral administration of drug (intravenously slowly or intramusculary) with the subsequent use of drug in the form of tablets or at once with use of tablets.
It is necessary to swallow of tablets without chewing. The tablets Geptrala are covered with a special cover which is dissolved only in intestines thanks to what ademetionin it is released in a duodenum. For the best absorption of active agent and full therapeutic effect the pill should be taken between meals. The tablet Geptrala should be taken out from the blister just before reception. In case of discoloration of tablets from initial from white to yellowish (owing to damage of an aluminum cover of the blister) it is necessary to refrain from their use.
Initial therapy (oral administration) the Recommended dose makes 10 25 mg/kg/day. The usual initial dose makes on 500 mg 1-2 times a day. The daily dose should not exceed 1500 mg.
Maintenance therapy: 2 3 tablets a day in (1000 1500 mg/day.)
Duration of therapy depends on weight and a course of the disease and is defined by the doctor individually.
Patients of advanced age.
Treatment is recommended to be begun with the smallest recommended dose, in view of decrease in hepatic, renal or warm function, existence of the accompanying morbid conditions and use of other medicines.
Use for patients with a renal failure
of Researches at patients with a renal failure was not carried out, in this regard it is recommended to be careful at use of an ademetionin for such patients.
Use for patients with a liver failure
the Parameters of pharmacokinetics of an ademetionin are similar at healthy volunteers and at patients to chronic diseases of a liver.
Side effects from clinical trials
Often (& ge, 1/100, & lt, 1/10)
– nausea, an abdominal pain, diarrhea
– a headache
– alarm, insomnia
– a skin itching
Infrequently (& ge, 1/1000, & lt, 1/100)
– dryness in a mouth, dyspepsia, a meteorism, gastrointestinal pain, gastrointestinal bleedings, gastrointestinal disorders, vomiting
– an asthenia, hypostasis, fever, a fever *, reactions in the place of an injection *, necrosis in the injection site *
– hypersensitivity, anaphylactoid reactions or anaphylactic reactions (for example, hyperaemia of integuments, an asthma, a bronchospasm, a dorsodynia, sensation of discomfort in breasts, change of arterial blood pressure (hypotonia, a hypertension) or pulse rate (tachycardia, bradycardia)) *
– infections of urinary tract
– arthralgias, muscular spasms
– dizziness, paresthesias
– agitation, confusion of consciousness
– a laryngeal edema *
– the increased sweating, a Quincke’s disease *, skin allergic reactions (for example, rash, a skin itching, a small tortoiseshell, an erythema) *
– inflows, hypotension, phlebitis
Seldom (& ge, 1/10000, & lt, 1/1000)
– an abdominal distension, an esophagitis
– an indisposition
* Undesirable effects of post-marketing use (spontaneous messages) which were not observed in clinical trials were referred to number of infrequent effects, on the basis of what the upper limit of 95% of a confidence interval of assessment of occurrence does not exceed 3/X where X = 2115 (total number of the subjects observed in clinical trials).
– hypersensitivity to any component of drug
– patients with the genetic defect influencing metabolism of methionine and/or a homocystinuria and/or a gipergomotsisteinemiya (for example, deficiency of enzyme tsistation sintetazy, defect of metabolism of B12 vitamin)
the message about development of a serotoninovy syndrome in the patient applying ademetionin and klomipramin Was beta. It is necessary to apply with care Geptral along with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as klomipramin), the drugs and vegetable means containing tryptophane.
At patients with pre-cirrhotic states and cirrhosis with a giperkreatininemiya it is necessary to control creatinine level during reception of the tablets Geptrala.
Insufficiency of B12 vitamin and folic acid can lead to reduction of concentration of an ademetionin therefore to patients of risk group (anemia, a liver failure, pregnancy or potential for a lack of vitamins because of other diseases or preferences in food, such as strict vegetarians) neokhodimo to carry out daily blood tests to check plasma levels. If insufficiency is found, treatment by B12 vitamin and folic acid is recommended along with use of an ademetionin.
Some patients at therapy ademetioniny can have a dizziness. It is not necessary to run vehicles or to work with other mechanisms before total disappearance of symptoms which can affect speed of response at the specified types of activity.
Geptral is not recommended for use for patients with bipolar psychoses. Messages about transition of a depression to a hypomania or mania at treatment were received ademetioniny.
Patsiyentov it is necessary to warn about need of informing the doctor if during therapy by Geptral the symptoms of their disease (depression) do not pass or worsen. Patients with a depression need careful observation and continuous mental health services at treatment ademetioniny for the purpose of control of efficiency of treatment.
One literary message about a serotoninovy syndrome at the patient receiving ademetionin and klomipramin was received. As the possibility of medicinal interaction is not excluded, it is necessary to apply with care Geptral along with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as klomipramin), the drugs and vegetable means containing tryptophane.
Messages about the tranzitorny or amplifying alarm at the patients receiving treatment Geptraly (ademetioniny) were received. In most cases, the treatment termination was not required. In certain cases the alarm stopped after a dose decline or the termination of therapy.
Ademetionin interacts with immunoassays for definition to a gomotsistein that can lead to false increase in level of a gomotsistein in blood plasma at the patients receiving treatment Geptraly (ademetioniny). At this category of patients it is recommended to use not immunological methods of determination of level of a gomotsistein in blood plasma.
The liver failure
of Dose adjustment is not required. It is necessary to control ammonia level at patients with a giperammoniyemiya.
The renal failure
Geptral to apply with care.
Use in pediatrics
Safety and efficiency of use of Geptral (ademetionina) for children up to 18 years are not established.
Pregnancy and the period of a lactation
Use of high doses of an ademetionin in ІІІ a trimester of pregnancy did not cause any side reactions. Geptral’s use in І a trimester of pregnancy is possible only in urgent cases.
In the period of a lactation Geptral is applied, only if the advantage of its use exceeds risk for the baby.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
there Can be dizziness. It is not necessary to run vehicles or to work with other mechanisms before total disappearance of symptoms which can affect speed of response at the specified types of activity.
Symptoms – strengthening of side effects.
Treatment – the general maintenance therapy against the background of observation of vital functions of an organism and a clinical condition of the patient.
The form of release and packing
On 10 tablets place in blister strip packaging from aluminum foil.
On 2 blister strip packagings together with the instruction for medical use in the state and Russian languages place in a pack from cardboard.
To Store storage conditions at a temperature not over 25C.
To store out of children’s reach!
not to use a period of storage after the expiry date specified on packing.
According to the prescription
of Abbvi of Neuter of l., Italy
Neuter 148 Pontina Km 52 snts 04011 Campoverda di Aprilia LT.
The owner of the registration certificate
of Abbott Laboratories S.A., Switzerland
(Neuhofstrasse 23, CH-6341 Baar Switzerland)
The address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods)
of Predstavitelstvo Abbott Laboratories S.A. in
Republic of Kazakhstan Almaty, Dostyk Ave., 117/6, BC Khan Tengri 2
ph.: +7 727 2447544
fax: +7 727 2447644