Samelix lyophilisate for injection with solvent 400mg, No. 5

• Intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, including: fatty degeneration of the liver; chronic hepatitis; toxic liver damage of various etiologies, including alcoholic, viral, medicinal (antibiotics, anticancer, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives); chronic acalculous cholecystitis; cholangitis; cirrhosis of the liver; encephalopathy, incl. associated with liver failure (including alcoholic).

• Intrahepatic cholestasis in pregnant women.

• Depression symptoms.

Administered orally, intramuscularly or intravenously (very slowly). When administered intravenously or intramuscularly, the daily dose is 400-800 mg.

The duration of treatment is set individually, depending on the severity and course of the disease.

In elderly patients, it is recommended to start treatment with the lowest recommended dose, taking into account the decrease in hepatic, renal or cardiac function, the presence of concomitant pathological conditions and the use of other drugs.

Lyophilisate for the preparation of a solution for intravenous and intramuscular administration in the form of a porous mass from almost white to white with a yellowish tinge of color with a characteristic odor; solvent: colorless to yellowish transparent liquid with a characteristic odor; solution: transparent colorless or slightly yellowish.

1 fl.

ademetionine 1.4-butanedisulfonate 760 mg,

which corresponds to the content of ademetionine 400 mg

1 ampoule of solvent contains: L-lysine monohydrate 384.5 mg (in terms of L-lysine 342.4 mg), sodium hydroxide solution 1M to pH 9.8-10.3, water for injection up to 5 ml.

Genetic disorders affecting the methionine cycle and / or causing homocystinuria and / or hyperhomocysteinemia (deficiency of cystathione beta synthetase, impaired cyanocobalamin metabolism); age up to 18 years, hypersensitivity to ademetionine.

pharmachologic effect

Hepatoprotector, has antidepressant activity. It has choleretic and cholekinetic effects. It has detoxifying, regenerating, antioxidant, anti-fibrosing and neuroprotective properties.

Replenishes the deficiency of ademetionine and stimulates its production in the body, primarily in the liver and brain. Participates in biological transmethylation reactions (methyl group donor) - S-adenosyl-L-methionine molecule (ademetionine), is a methyl group donor in methylation reactions of cell membrane phospholipids, proteins, hormones, neurotransmitters; participates in transsulfation reactions as a precursor of cysteine, taurine, glutathione (provides the redox mechanism of cellular detoxification), acetylation coenzyme. Increases the content of glutamine in the liver, cysteine ??and taurine in plasma; reduces the content of methionine in serum, normalizing metabolic reactions in the liver.In addition to decarboxylation, it participates in aminopropylation processes as a precursor of polyamines - putrescine (stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure.

It has a choleretic effect due to an increase in the mobility and polarization of the membranes of hepatocytes, due to the stimulation of the synthesis of phosphatidylcholine in them. This improves the function of the bile acid transport systems associated with the hepatocyte membranes and facilitates the passage of bile acids into the biliary system. Effective for intralobular cholestasis (violation of the synthesis and flow of bile). Promotes detoxification of bile acids, increases the content of conjugated and sulfated bile acids in hepatocytes. Conjugation with taurine increases the solubility of bile acids and their excretion from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates the passage through the membrane of the hepatocyte and excretion with bile. Besides,sulfated bile acids protect the liver cell membranes from the toxic effects of unsulfated bile acids (present in high concentrations in hepatocytes in intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of pruritus and changes in biochemical parameters, incl. direct bilirubin level, alkaline phosphatase activity, aminotransferases.

Pharmacokinetics

After a single oral dose of 400 mg, Cmax of ademetionine in plasma is reached after 2-6 hours and is 0.7 mg / l. The bioavailability of the drug when taken orally is 5%, with i / m administration - 95%.

Serum protein binding is negligible.

Penetrates the BBB. Regardless of the route of administration, there is a significant increase in the concentration of ademetionine in the cerebrospinal fluid. It is metabolized in the liver. T1 / 2 - 1.5 hours. It is excreted in the kidneys.

Side effect

From the digestive system: often - nausea, abdominal pain, diarrhea; rarely - vomiting, dry mouth, esophagitis, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, hepatic colic.

From the nervous system: rarely - confusion, insomnia, dizziness, headache, paresthesia.

From the musculoskeletal system: rarely - arthralgia, muscle cramps.

From the urinary system: rarely - urinary tract infections.

From the side of the skin: rarely - hyperhidrosis, itching, skin rash.

Local reactions: rarely - reactions at the injection site; very rarely - reactions at the injection site, skin necrosis at the injection site.

Allergic reactions: rarely - anaphylactic reactions; very rarely - Quincke's edema, laryngeal edema.

Others: rarely - hot flashes, superficial phlebitis, asthenia, chills, flu-like symptoms, weakness, peripheral edema, hyperthermia.

Application during pregnancy and lactation

In the I and II trimesters of pregnancy, ademetionine is used only if absolutely necessary, when the expected benefit to the mother outweighs the potential risk to the fetus. The use of ademetionine in high doses in the third trimester of pregnancy did not cause any undesirable effects.

The use of ademetionine during breastfeeding is possible only if the expected benefit to the mother outweighs the potential risk to the child.

Application for violations of liver function

The drug is approved for use in case of impaired liver function

Application in children

Contraindication: children and adolescents up to 18 years of age.

special instructions

Use ademetionine with caution in patients with renal failure, with bipolar disorders, simultaneously with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine); herbal preparations and preparations containing tryptophan; in elderly patients.

Deficiency of vitamin B12 and folic acid can lead to a decrease in ademetionine concentrations, therefore, their concomitant use in normal doses is recommended.

Patients with depression require close supervision and constant psychiatric care during treatment with ademetionine in order to monitor the effectiveness of treatment.

When used in patients with cirrhosis of the liver against the background of hyperazotemia, systematic monitoring of the level of nitrogen in the blood is required. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.

Influence on the ability to drive vehicles and use mechanisms

Dizziness is possible when using ademetionine. Patients should not drive vehicles or work with other mechanisms until the symptoms disappear completely, which may affect the reaction rate during these activities.

Drug interactions

There is a report on the development of serotonin syndrome in a patient who used ademetionine and clomipramine.

Caution should be exercised when using ademetionine simultaneously with selective serotonin reuptake inhibitors, tricyclic antidepressants, drugs and herbal remedies containing tryptophan.