Samelix tablets p / o 400mg, No. 20

• Intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
  - 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 (alcoholic, etc.);

• Intrahepatic cholestasis in pregnant women;

• Depression symptoms.

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

Dosage 400 mg
1 enteric film-coated tablet contains:
Active ingredient: ademetionine 1,4-butanedisulfonate 760 mg (in terms of ademetionine 400 mg);
excipients: sodium carboxymethyl starch 18 mg, colloidal silicon dioxide 9 mg, magnesium stearate 4.5 mg, microcrystalline cellulose 108.5 mg;
composition of the film shell: Opadray transparent 15 mg, including: hypromellose (hydroxypropyl methylcellulose) 12 mg, macrogol (polyethylene glycol) 3 mg; Acryl-Iz white 60 mg, including: methacrylic acid and ethyl acrylate copolymer [1: 1] 39.6 mg, colloidal silicon dioxide 0.6 mg, sodium bicarbonate 0.6 mg, sodium lauryl sulfate 0.3 mg, talc 9 , 9 mg, titanium dioxide 9 mg; Triethyl citrate 5 mg.

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

• Hypersensitivity to any component of the drug;

• Age up to 18 years (experience of medical use in children is limited).

Carefully

Bipolar disorder (see section 'Special instructions').
Pregnancy (I trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother outweighs 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 preparations and preparations containing tryptophan (see section 'Interaction with other drugs').
Elderly age.
Renal failure

Trade name:

SamelixЃ

International non-proprietary or group name:

ademetionine

Dosage form:

enteric tablets, film-coated.

Composition

Dosage 400 mg
1 enteric film-coated tablet contains:
Active ingredient: ademetionine 1,4-butanedisulfonate 760 mg (in terms of ademetionine 400 mg);
excipients: sodium carboxymethyl starch 18 mg, colloidal silicon dioxide 9 mg, magnesium stearate 4.5 mg, microcrystalline cellulose 108.5 mg;
composition of the film shell: Opadray transparent 15 mg, including: hypromellose (hydroxypropyl methylcellulose) 12 mg, macrogol (polyethylene glycol) 3 mg; Acryl-Iz white 60 mg, including: methacrylic acid and ethyl acrylate copolymer [1: 1] 39.6 mg, colloidal silicon dioxide 0.6 mg, sodium bicarbonate 0.6 mg, sodium lauryl sulfate 0.3 mg, talc 9 , 9 mg, titanium dioxide 9 mg; Triethyl citrate 5 mg.

Description

Tablets are oval, biconvex, film-coated, white or almost white.

Pharmacotherapeutic group:

hepatoprotective agent.

ATX code:

A16AA02.

Pharmacological properties

Pharmacodynamics
Ademetionine belongs to the group of hepatoprotectors, it also has antidepressant activity. It has choleretic and cholekinetic effects, has detoxifying, regenerating, antioxidant, anti-fibrosing and neuroprotective properties. Replenishes the deficiency of S-adenosyl-L-methionine (ademetionine) and stimulates its production in the body, is found in all environments of the body. The highest concentration of ademetionine was found in the liver and brain. Plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transsulfation, transamination. In transmethylation reactions, ademetionine donates a methyl group for the synthesis of phospholipids of cell membranes, neurotransmitters, nucleic acids, proteins, hormones, etc.In transsulfation reactions, ademetionine is a precursor of cysteine, taurine, glutathione (providing the redox mechanism of cellular detoxification), coenzyme A (involved in the biochemical reactions of the tricarboxylic acid cycle and replenishes the energy potential of the cell). 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. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis. It has a choleretic effect.glutathione (providing the redox mechanism of cellular detoxification), coenzyme A (involved in the biochemical reactions of the tricarboxylic acid cycle and replenishes the energy potential of the cell). 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. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis. It has a choleretic effect.glutathione (providing the redox mechanism of cellular detoxification), coenzyme A (involved in the biochemical reactions of the tricarboxylic acid cycle and replenishes the energy potential of the cell). 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. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis. It has a choleretic effect.plasma cysteine ??and taurine; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis. It has a choleretic effect.plasma cysteine ??and taurine; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis. It has a choleretic effect.
Ademetionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases the fluidity and polarization of membranes. This improves the function of the bile acid transport systems associated with the membranes of hepatocytes and promotes the passage of bile acids into the bile ducts. Effective for intralobular cholestasis (violation of the synthesis and flow of bile). Ademetionine reduces the toxicity of bile acids in the hepatocyte, carrying out their conjugation and sulfation. 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,the sulfated bile acids themselves additionally protect the liver cell membranes from the toxic effects of unsulfated bile acids (in high concentrations present in hepatocytes during intrahepatic cholestasis).
In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, ademetionine reduces the severity of pruritus and changes in biochemical parameters, incl. the level of direct bilirubin, the activity of alkaline phosphatase, aminotransferases, etc. The choleretic and hepatoprotective effect lasts up to 3 months after stopping treatment.
It has been shown to be effective in hepatopathies caused by various hepatotoxic drugs. Prescribing to patients with opioid addiction, accompanied by liver damage, leads to a regression of clinical manifestations of abstinence, an improvement in the functional state of the liver and microsomal oxidation processes.
Antidepressant activity manifests itself gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. Effective for recurrent endogenous and neurotic depression resistant to amitriptyline. Has the ability to interrupt relapses of depression. Ademetionine increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.

Pharmacokinetics The
tablets are film-coated, dissolving only in the intestine, due to which ademetionine is released in the duodenum.
Absorption
Oral bioavailability - 5%, increases when taken on an empty stomach. The maximum plasma concentrations (Cmax) of ademetionine are dose-dependent and amount to 0.5-1 mg / l 3-5 hours after a single oral administration in doses from 400 to 1000 mg. Cmax of ademetionine in plasma decreases to the initial level within 24 hours.
Distribution
Bond with blood plasma proteins - insignificant, is? 5%, penetrates the blood-brain barrier. There is a significant increase in the concentration of the drug in the cerebrospinal fluid.
Metabolism
It is metabolized in the liver. The process of formation, consumption and re-formation of ademetionine is called the ademetionine cycle. At the first stage of this cycle, ademetionine-dependent methylases use ademetionine as a substrate for the production of S-adenosyl homocysteine, which is then hydrolyzed to homocysteine ??and adenosine by S-adenosyl homocysteine ??hydralase. Homocysteine, in turn, undergoes reverse transformation to methionine by transfer of a methyl group from 5-methyltetrahydrofolate. Eventually, methionine can be converted to ademetionine, completing the cycle.
Withdrawal
The half-life (T1 / 2) is 1.5 hours. It is excreted by the kidneys. In studies in healthy volunteers, when ingestion of labeled (methyl 14C) S-adenosyl-L-methionine, 15.5 ± 1.5% of radioactivity was detected in urine after 48 hours, and in feces - 23.5 ± 3.5% of radioactivity after 72 hours. Thus, about 60% was deposited.

Indications for use

• Intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
  - 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 (alcoholic, etc.);

• Intrahepatic cholestasis in pregnant women;

• Depression symptoms.

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 component of the drug;

• Age up to 18 years (experience of medical use in children is limited).

Carefully

Bipolar disorder (see section 'Special instructions').
Pregnancy (I trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother outweighs 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 preparations and preparations containing tryptophan (see section 'Interaction with other drugs').
Elderly age.
Renal failure

Application during pregnancy and during breastfeeding

In clinical studies, it was shown that the use of ademetionine in the third trimester of pregnancy did not cause any undesirable effects.
The use of SamelixЃ in pregnant women in the I and II trimesters and during breastfeeding is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child.

Method of administration and dosage

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

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.

Overdose

Overdose of SamelixЃ is unlikely. In case of an overdose, it is recommended to monitor the patient and conduct symptomatic therapy.

Interaction with other medicinal products

No known interactions with other drugs have been observed.
There is a report of the serotonin excess syndrome in a patient taking ademetionine and clomipramine. It is believed that such an interaction is possible, and caution should be exercised when administering ademetionine in conjunction with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), and herbs and drugs containing tryptophan.

special instructions

Given the tonic effect of the drug, it is not recommended to take it before bedtime. When the drug SamelixЃ is prescribed to patients with cirrhosis of the liver against the background of hyperazotemia, systematic monitoring of the nitrogen content in the blood is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.
It is not recommended to use ademetionine in patients with bipolar disorder. There are reports of the transition of depression to hypomania or mania in patients taking ademetionine.
Patients with depression have an increased risk of suicide and other serious adverse events, therefore, during treatment with ademetionine, such patients should be under constant medical supervision to evaluate and treat symptoms of depression. Patients should inform the doctor if their symptoms of depression do not decrease or worsen with ademetionine therapy.
There are also reports of a sudden onset or increase in anxiety in patients taking ademetionine. In most cases, withdrawal of therapy is not required; in several cases, the anxiety disappeared after dose reduction or drug withdrawal.
Since a deficiency of cyanocobalamin and folic acid can reduce the content of ademetionine in patients at risk (with anemia, liver disease, pregnancy or the likelihood of vitamin deficiency, due to other diseases or diet, for example, in vegetarians), the content of vitamins in the blood plasma should be monitored. If a deficiency is found, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademetionine or concurrently with ademetionine.
In immunological analysis, the use of ademetionine can contribute to a false determination of the indicator of high levels of homocysteine ??in the blood.
For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine the content of homocysteine.
Children
The safety of using SamelixЃ in children has not been sufficiently studied.

Influence on the ability to drive vehicles, mechanisms

Some patients may experience dizziness while taking SamelixЃ. It is not recommended to drive a car and work with mechanisms while taking the drug until patients are sure that the therapy does not affect the ability to engage in this type of activity.

Release form

Enteric-soluble tablets, film-coated, 400 mg 10 tablets in a blister strip made of polyvinyl chloride film or PVC / PVDC film and lacquered aluminum foil.
1, 2, 4 blister packs, together with instructions for use, are placed in a cardboard box.

Storage conditions

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

Shelf life

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

Vacation conditions

Dispensed by prescription.

Legal entity in whose name the registration certificate was issued

Bakter LLC, Russia.
107014, Moscow, st. Babaevskaya, 6.

Information about organizations to which claims on the quality of the medicinal product can be sent

Bakter LLC, Russia.
107014, Moscow, st. Babaevskaya, 6.

Manufacturer

CJSC 'Kanonfarma production'
Russia, 141100, Moscow region, Shchelkovo, st. Zarechnaya, 105.