Ademethionine refers to hepatic group also has antidepressant activity. It has choleretic and holekineticheskoe action has detoxifying, regenerating, antioxidant, antifibroziruyuschimi and neuroprotective properties.
Fills deficit S-adenosyl-L-methionine (ademetionine) and stimulate its production in an organism, contained in all the environments of the body. The highest concentration of ademetionina observed in the liver and brain. Performs a key role in the metabolic processes of the body, is involved in important biochemical reactions: transmethylation, transsulfuration, transamination. In the reactions of transmethylation ademetionine donates a methyl group to the synthesis of phospholipids of cell membranes, neurotransmitters, nucleic acids, proteins, hormones, and others. The reaction transsulfatirovaniya ademetionine is a precursor of cysteine, taurine, glutathione (providing redox mechanism cell detoxifying) coenzyme acetylation (included in biochemical reactions TCA cycle and replenishes the energy potential of the cells).Increases of hepatic glutamine, cysteine and taurine in plasma; reduces the serum methionine, normalizing the metabolic reactions in the liver. After participating in the decarboxylation reactions aminopropilirovaniya, as a precursor of polyamines – putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, within the structure of the ribosome, which reduces the risk of fibrosis. It has choleretic effect. Ademethionine normalize endogenous phosphatidylcholine synthesis in hepatocytes, which increases the fluidity and membrane polarization. This improves the function associated with the membranes of hepatocytes bile acid transport systems and facilitates passage of bile acids in the biliary system. Effective with intrahepatic (Lobular and interlobular) version of cholestasis (impaired synthesis and bile flow). Ademethionine reduces the toxicity of bile acids in the hepatocyte, exercising their sulfation and conjugation. Conjugation with taurine increases the solubility of bile acids and removing them from the hepatocyte. The process of sulfation of bile acids helps to eliminate the possibility of their kidneys, facilitates the passage through the membrane of hepatocytes and excretion of bile. In addition, the sulfated bile acids themselves also protect the liver cell membrane from toxic effects of non-sulfated bile acids (present in high concentration in the hepatocytes in intrahepatic cholestasis). In patients with diffuse liver disease (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome ademetionine reduces the severity of itching and changes in biochemical parameters, including the level of direct bilirubin, alkaline phosphatase, aminotransferases and others. choleretic and hepatoprotective effect lasts up to 3 months after stopping treatment. The efficiency with hepatopathies caused by a variety of hepatotoxic drugs. Appointment of patients with opioid addiction, accompanied by lesions of the liver, resulting in regression of clinical manifestations of abstinence, improving the functional state of the liver and microsomal oxidation processes. The antidepressant activity manifested gradually, starting from the end of the first week of treatment and stabilized for 2 weeks of treatment. Effective with recurrent endogenous and neurotic masteron prop resistant to amitriptyline. It has the ability to interrupt the relapse of masteron prop. Assignment reduces the severity of osteoarthritis in pain syndrome, increase proteoglycan synthesis and leads to a partial regeneration of cartilage tissue.
Bioavailability when administered parenterally – 96% in the plasma concentration reaches maximum values after 45 minutes. It is metabolized in the liver. Contact with blood plasma proteins – small. It penetrates through the blood-brain barrier. Ademetionine been a significant increase in the CSF concentrations.
The half-life time (the T 1/2 ) -. 1.5 hours excreted by the kidneys.
- Intrahepatic cholestasis during pretsirroticheskih and cirrhotic conditions, which may occur in the following diseases:
- fatty liver;
- chronic hepatitis;
- Toxic liver disease of various etiologies, including alcohol, virus, medicines (antibiotics, anti-cancer, anti-tuberculosis and anti-viral drugs, tricyclic antidepressants, oral contraceptives);
- chronic cholecystitis without stones;
- cirrhosis of the liver;
- encephalopathy, including associated with hepatic insufficiency (alcohol, etc.).
- Intrahepatic cholestasis in pregnancy.
- Symptoms of masteron prop.
Hypersensitivity to any component of the drug.
Age up to 18 years.
Bipolar disorder (see. “Special Instructions” section).
Pregnancy (I term).
The period of lactation.
Application of pregnancy and during breastfeeding
The use of high doses of ademetionina in the III trimester of pregnancy did not cause any adverse effects. Use of the drug Geptral ® in pregnant women in the I trimester and during breast-feeding is possible only if the potential benefit to the mother outweighs the potential risk to the fetus or child.
Dosing and Administration
Intravenously and intramuscularly.
Dissolving the lyophilisate in need specially attached solvent just prior to administration. The residue of the drug is to be disposed of.
The drug should not be mixed with alkaline solutions and solutions containing calcium ions.
The drug Geptral ® for intravenous use is introduced very slowly.
From 400 mg / day to 800 mg / day (1-2 vial day) for 2 weeks.
400 mg / day (one bottle per day) during 15-20 days.
If necessary maintenance therapy to continue taking the drug Geptral ® as tablets in dose of 800-1600 mg / day for 2-4 weeks.
Among the most frequent adverse reactions observed: nausea, abdominal pain and diarrhea. Following are summary data on adverse reactions that were observed during treatment with ademetionina both tablets and injectable dosage form.
Immune system : laryngeal edema, allergic reactions.
Skin: injection site reactions (very rare skin necrosis), sweating, itching, rash, angioedema, skin reactions.
Infections and infestations: urinary tract infection.
From the nervous system : dizziness, headache, paresthesia, confusion, and insomnia.
Cardio-vascular system: hot flashes, phlebitis of superficial veins, cardiovascular disorders.
From the digestive system: abdominal distension, abdominal pain, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastrointestinal disorder, gastrointestinal bleeding, nausea, vomiting, hepatic colic, hepatic cirrhosis.
From the musculoskeletal system : arthralgia, muscle cramps .
Other : asthenia, chills, injection site reactions, flu-like symptoms, malaise, peripheral edema, fever.
Clinical cases of overdose were reported.
Interaction with other drugs
Known interactions with other drugs have been observed.
There are reports of a syndrome of excess serotonin in patients taking ademetionine and clomipramine. It is believed that such an interaction is possible and should be used with caution in ademetionine with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbs and drugs containing tryptophan.
Given the invigorating effect of the drug is not recommended to take it at bedtime. In appointing the drug Geptral ® in patients with cirrhosis of the liver on the background hyperasotemia requires systematic monitoring of nitrogen levels in the blood. During long-term therapy is necessary to determine the content of urea and creatinine in the blood serum.
Do not appoint ademetionine patients with bipolar disorder. There are reports about the transition masteron prop hypomania or mania in patients taking ademetionine.
Patients taking Geptral ® , is recommended to prescribe B12 and folic acid deficiency as tsianokobalomina (vitamin B12) and folic acid can reduce the concentration of ademetionina.
The safety of the drug Geptral ® in children poorly understood.
Effects on ability to drive and use machines
In some patients when taking the drug Geptral ® can be dizziness. Do not drive a car and operate machinery while taking the drug for as long as patients are confident that the therapy does not affect the ability to engage in this type of activity.