Samelix Lyophilizate 400mg vials, 5pcs

Composition

1 bottle of lyophilizate contains: Active ingredient: ademetionine 1,4-butane disulfonate 760.0 mg, in terms of ademetionine 400.0 mg. 1 ampoule of solvent contains: L-lysine monohydrate 384.5 mg, in terms of L-lysine 342.4 mg, sodium hydroxide solution of 1 M to pH 9.8-10.3, water for injection up to 5 ml

Pharmacological action

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

It makes up for ademetionine deficiency and stimulates its production in the body, primarily in the liver and brain. Participates in biological transmethylation reactions ( methyl group donator)-a molecule of S-adenosyl-L-methionine (ademetionine), is a methyl group donator in methylation reactions of phospholipids of cell membranes, proteins, hormones, neurotransmitters; participates in transulfation reactions as a precursor of cysteine, taurine, glutathione (provides the redox mechanism of cellular detoxification), coenzyme acetylation.

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 the processes of aminopropylation as a precursor of polyamines-putrescine (a stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure.

It has a choleretic effect due to increased mobility and polarization of hepatocyte membranes, due to stimulation of phosphatidylcholine synthesis in them. This improves the function of bile acid transport systems associated with hepatocyte membranes and promotes the passage of bile acids into the biliary system. It is effective for intralobular cholestasis (violation of bile synthesis and flow).

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 removal from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates passage through the membrane of the hepatocyte and excretion with bile.

In addition, sulfated bile acids protect the liver cell membranes from the toxic effects of unsulfated bile acids (in high concentrations present 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, including the level of direct bilirubin, alkaline phosphatase activity, and aminotransferases.

Pharmacokinetics

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

Binding to serum proteins is negligible.

Penetrates through the BBB. Regardless of the route of use, there is a significant increase in the concentration of ademetionine in the cerebrospinal fluid. It is metabolized in the liver. T_1/2-1.5 h. Excreted by the kidneys.

Indications

• Intrahepatic cholestasis in precirrotic and cirrhotic conditions, which can be observed in the following diseases:

– fatty liver disease; – chronic hepatitis;- toxic liver damage of various etiologies, including alcoholic, viral, medicinal (antibiotics, antitumor, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives);- chronic stone-free cholecystitis;- cholangitis;- cirrhosis of the liver; – encephalopathy, including those associated with liver failure (alcohol, etc. );

• Intrahepatic cholestasis in pregnant women;

• Symptoms of depression.

Use during pregnancy and lactation

In the first and second trimesters of pregnancy, ademetionine is used only when absolutely necessary, when the expected benefit to the mother exceeds 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 exceeds the potential risk to the child.

Recommendations for use

Apply inside, in / m or in/v (very slowly. )

When taken orally, the daily dose is 800-1600 mg.

With intravenous or intramuscular use, the daily dose is 400-800 mg.

The duration of treatment is determined 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 liver, renal or cardiac function, the presence of concomitant pathological conditions and the use of other medications.

Contraindications

Genetic disorders affecting the methionine cycle and / or causing homocystinuria and / or hyperhomocysteinemia (cystathionine beta-synthase deficiency, impaired vitamin B12 metabolism);

Hypersensitivity to any of the components of the drug;

Under 18 years of age (limited medical experience in children).

With caution

• Bipolar disorders.
• Pregnancy (First trimester) and breast-feeding (use is possible only if the potential benefit to the mother exceeds the possible risk to the fetus and child).
• Concomitant use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), as well as herbal and tryptophan-containing medications.
• Advanced age.
• Kidney failure.

Side effects

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

Nervous system disorders:  rarely – confusion, insomnia, dizziness, headache, paresthesia.

Musculoskeletal disorders:  rarely-arthralgia, muscle cramps.

From the urinary system:  rarely-urinary tract infections.

From the side of the skin:  rarely – hyperhidrosis, pruritus, skin rash.

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

Allergic reactions:  rarely – anaphylactic reactions; very rarely-angioedema, laryngeal edema.

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

Interaction

Serotonin syndrome has been reported in a patient treated with ademetionine and clomipramine.

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

Special instructions

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

Lack of vitamin_B12 and folic acid can lead to a decrease in ademetionine concentrations, so their concomitant use in normal doses is recommended.

Patients with depression need close monitoring and ongoing psychiatric care during treatment with ademetionine in order to monitor the effectiveness of treatment.

When used in patients with cirrhosis of the liver on the background of hyperazotemia, systematic monitoring of blood nitrogen levels is necessary. 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 motor vehicles and manage mechanisms

When using ademetionine, dizziness may occur. Patients should not drive vehicles or operate other machinery until symptoms that may affect the response rate to these activities have completely disappeared.

Active ingredient

Ademetionine

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion