Samelix 400mg enteric-Soluble tablets, 20pcs

Composition

1 enteric-soluble film-coated tablet contains: Active ingredient: ademetionine 1,4-butane disulfonate 760 mg (based on ademetionine 400 mg); Excipients: sodium carboxymethyl starch 18 mg, colloidal silicon dioxide 9 mg, magnesium stearate 4.5 mg, microcrystalline cellulose 108.5 mg; film shell composition:  Opadry transparent 15 mg, including: hypromellose (hydroxypropyl methylcellulose) 12 mg, macrogol (polietilenglikol) 3 mg; Acrylic From white 60 mg, including: methacrylic acid and ethylacrylate copolymer [1: 1] of 39.6 mg, silicon dioxide colloid 0.6 mg, sodium bicarbonate 0.6 mg, sodium lauryl sulfate 0.3 mg, talc and 9.9 mg, titanium dioxide 9 mg; 5 mg. Triethylcitrate

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.

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.

How to take, course of use and dosage

Inside. Tablets should be taken whole, without chewing, preferably in the morning between meals. Tablets of Samelix® should be removed from the blister immediately before ingestion. If the tablets have a color other than white to white with a yellowish tinge (due to leakage of aluminum foil), Samelix® should not be used. Initial therapy The recommended dose is 10-25 mg / kg / day. Intrahepatic cholestasis ranges from 800 mg / day to 1600 mg / day. Depressivation ranges from 800 mg / day to 1600 mg / day. The duration of therapy is determined by the doctor. Ademetionine therapy can be initiated by intravenous or intramuscular use, followed by the use of Samelix® in tablet form, or immediately with the use of Samelix® in tablet form. Elderly patients Clinical experience with Samelix® did not reveal any differences in its effectiveness in elderly patients and younger patients. However, given the high probability of existing liver, kidney or heart disorders, other comorbidities, or concomitant therapy with other medications, the dose of Samelix® in elderly patients should be selected with caution, starting with the lower limit of the dose range. Renal insufficiency There are limited clinical data on the use of ademetionine in patients with renal insufficiency, and therefore caution is recommended when using Samelix® in such patients. Hepatic insufficiency The pharmacokinetic parameters of ademetionine are similar in healthy volunteers and in patients with chronic liver disease. Children The use of Samelix® in children is contraindicated (efficacy and safety have not been established).

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.

Storage conditions

At a temperature not exceeding 25°C in the manufacturer’s packaging. Keep out of reach of children.

Shelf

life is 2 years. Do not use the drug after the expiration date.

Active ingredient

Ademetionine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets