Product Overview
Composition
Each tablet contains:
Active ingredient:
Ademethionine 1,4-butanedisulfonate 760 mg (corresponding to 400 mg of ademethionine ion).
Excipients: colloidal silicon dioxide - 4.4 mg, microcrystalline cellulose - 93.6 mg, sodium carboxymethyl starch (type A) - 17.6 mg, magnesium stearate - 4.4 mg;
Tablet shell: methacrylic acid and ethyl acrylate copolymer (1: 1) - 27.6 mg, macrogol-6000 - 8.07 mg, polysorbate-80 - 0.44 mg, simethicone (emulsion 30%) - 0.13 mg, sodium hydroxide - 0.36 mg, talc - 18.4 mg, water - QS
Active ingredient:
Ademethionine 1,4-butanedisulfonate 760 mg (corresponding to 400 mg of ademethionine ion).
Excipients: colloidal silicon dioxide - 4.4 mg, microcrystalline cellulose - 93.6 mg, sodium carboxymethyl starch (type A) - 17.6 mg, magnesium stearate - 4.4 mg;
Tablet shell: methacrylic acid and ethyl acrylate copolymer (1: 1) - 27.6 mg, macrogol-6000 - 8.07 mg, polysorbate-80 - 0.44 mg, simethicone (emulsion 30%) - 0.13 mg, sodium hydroxide - 0.36 mg, talc - 18.4 mg, water - QS
pharmachologic effect
Ademethionine belongs to the group of hepatoprotectors, also has antidepressant activity. It has a choleretic and cholekinetic effect, has detoxification, regenerating, antioxidant, antifibrosing and neuroprotective properties.
It compensates for the deficiency of S-adenosyl-L-methionine (ademethionine) and stimulates its production in the body, found in all body environments. The highest concentration of ademetionine is noted in the liver and brain. It plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transulfurization, transamination.
In the transmethylation reactions, ademetionine donates a methyl group for the synthesis of phospholipids of cell membranes, neurotransmitters, nucleic acids, proteins, hormones, etc. In the transulfurization reactions, ademethionine is a precursor of cysteine, taurine, glutathione (providing the redox mechanism of cellular detoxification (included) 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 serum methionine, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation reactions, as a precursor of polyamines - putrescine (a stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis.
It has a choleretic effect. Ademethionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases the fluidity and polarization of the membranes. This improves the function of the bile acid transport systems associated with the hepatocyte membranes and promotes the passage of bile acids into the bile ducts.
Effective with intralobular cholestasis (impaired synthesis and bile flow). Ademethionine reduces the toxicity of bile acids in hepatocytes by conjugating and sulfating them. Conjugation with taurine increases the solubility of bile acids and their removal from hepatocyte. The process of sulfation of bile acids promotes the possibility of elimination by the kidneys, facilitates the passage through the membrane of hepatocyte and excretion with bile. In addition, sulfated bile acids themselves additionally protect the liver cell membranes from the toxic effects of unsulfated bile acids (in high concentrations present in hepatocytes with intrahepatic cholestasis).
In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, ademetionine reduces the severity of skin itching and changes in biochemical parameters, including direct bilirubin concentrations, alkaline phosphatase activity, aminotransferases, etc. The choleretic and hepatoprotective effect persists for up to 3 months after discontinuation of treatment. It has been shown to be effective in hepatopathies caused by various hepatotoxic drugs. Antidepressant activity manifests itself gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment.
A number of studies have confirmed the effectiveness of ademetionine in the treatment of fatigue in patients with chronic liver disease. A pooled analysis of the data obtained in patients with symptoms of increased fatigue before starting treatment proved the effect of ademetionine treatment in reducing the symptoms of increased fatigue in combination with a number of other symptoms, such as depression, icteric skin and mucous membranes, malaise, and skin itching.
Ademethionine treatment significantly improved mood in patients with alcoholic liver disease, who simultaneously achieved a positive response from symptoms of increased fatigue. In addition, in patients with alcoholic liver disease and non-alcoholic fatty liver disease with an achieved response to ademetionine treatment from symptoms of increased fatigue, there was also a significant decrease in symptoms such as ictericity of the skin and mucous membranes, malaise, and skin itching.
It compensates for the deficiency of S-adenosyl-L-methionine (ademethionine) and stimulates its production in the body, found in all body environments. The highest concentration of ademetionine is noted in the liver and brain. It plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transulfurization, transamination.
In the transmethylation reactions, ademetionine donates a methyl group for the synthesis of phospholipids of cell membranes, neurotransmitters, nucleic acids, proteins, hormones, etc. In the transulfurization reactions, ademethionine is a precursor of cysteine, taurine, glutathione (providing the redox mechanism of cellular detoxification (included) 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 serum methionine, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation reactions, as a precursor of polyamines - putrescine (a stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis.
It has a choleretic effect. Ademethionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases the fluidity and polarization of the membranes. This improves the function of the bile acid transport systems associated with the hepatocyte membranes and promotes the passage of bile acids into the bile ducts.
Effective with intralobular cholestasis (impaired synthesis and bile flow). Ademethionine reduces the toxicity of bile acids in hepatocytes by conjugating and sulfating them. Conjugation with taurine increases the solubility of bile acids and their removal from hepatocyte. The process of sulfation of bile acids promotes the possibility of elimination by the kidneys, facilitates the passage through the membrane of hepatocyte and excretion with bile. In addition, sulfated bile acids themselves additionally protect the liver cell membranes from the toxic effects of unsulfated bile acids (in high concentrations present in hepatocytes with intrahepatic cholestasis).
In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, ademetionine reduces the severity of skin itching and changes in biochemical parameters, including direct bilirubin concentrations, alkaline phosphatase activity, aminotransferases, etc. The choleretic and hepatoprotective effect persists for up to 3 months after discontinuation of treatment. It has been shown to be effective in hepatopathies caused by various hepatotoxic drugs. Antidepressant activity manifests itself gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment.
A number of studies have confirmed the effectiveness of ademetionine in the treatment of fatigue in patients with chronic liver disease. A pooled analysis of the data obtained in patients with symptoms of increased fatigue before starting treatment proved the effect of ademetionine treatment in reducing the symptoms of increased fatigue in combination with a number of other symptoms, such as depression, icteric skin and mucous membranes, malaise, and skin itching.
Ademethionine treatment significantly improved mood in patients with alcoholic liver disease, who simultaneously achieved a positive response from symptoms of increased fatigue. In addition, in patients with alcoholic liver disease and non-alcoholic fatty liver disease with an achieved response to ademetionine treatment from symptoms of increased fatigue, there was also a significant decrease in symptoms such as ictericity of the skin and mucous membranes, malaise, and skin itching.
Indications
- Intrahepatic cholestasis in precirrotic and cirrhotic conditions, which can be observed with the following diseases:
- fatty liver disease;
- chronic hepatitis;
- toxic liver lesions of various etiologies, including alcoholic, viral, medicinal (antibiotics; antitumor, anti-TB and antiviral drugs, tricyclic antidepressants, oral contraceptives);
- chronic stoneless cholecystitis;
- cholangitis;
- cirrhosis of the liver;
- encephalopathy, including associated with liver failure (alcohol, etc.).
- Intrahepatic cholestasis in pregnant women.
- Symptoms of Depression
- Fatigue in chronic liver diseases.
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.
Age up to 18 years (medical experience in children is limited).
Bipolar disorder.
Carefully
Hypersensitivity to any of the components of the drug.
Age up to 18 years (medical experience in children is limited).
Bipolar disorder.
Carefully
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 or child).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), as well as herbal and tryptophan-containing drugs.
Elderly age.
Renal failure.
Interaction
No known interactions with other drugs have been observed.
There is a report of an excess serotonin syndrome in a patient taking ademetionine and clomipramine. It is believed that this interaction is possible and caution should be given to ademetionine along with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbs and drugs containing tryptophan.
There is a report of an excess serotonin syndrome in a patient taking ademetionine and clomipramine. It is believed that this interaction is possible and caution should be given to ademetionine along with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbs and drugs containing tryptophan.
How to take, course of administration and dosage
Inside.
Tablets should be taken whole without chewing, preferably in the morning between meals.
Heptral® tablets should be removed from the blister just before oral administration. If the tablets have a color other than white to white with a yellowish tint (due to leaks in aluminum foil), Heptral® is not recommended.
Initial therapy
Tablets should be taken whole without chewing, preferably in the morning between meals.
Heptral® tablets should be removed from the blister just before oral administration. If the tablets have a color other than white to white with a yellowish tint (due to leaks in aluminum foil), Heptral® is not recommended.
Initial therapy
The recommended dose is 10-25 mg / kg / day by mouth.
Intrahepatic cholestasis / fatigue in chronic liver diseases The
dose is from 800 mg / day to 1600 mg / day.
Depression
The dose is from 800 mg / day to 1600 mg / day.
The duration of therapy is determined by the doctor.
Heptral® therapy can be started with intravenous or intramuscular administration followed by the use of Heptral® in the form of tablets or immediately with the use of Heptral® in the form of tablets.
Elderly patients
Clinical experience with the use of the drug Heptral® did not reveal any differences in its effectiveness in elderly patients and patients of a younger age. However, given the high likelihood of existing impaired liver, kidney, or heart function, other concomitant pathology, or simultaneous therapy with other drugs, the dose of Heptral® should be selected with caution for elderly patients, starting with the lower limit of the dose range.
Renal failure
There is limited clinical data on the use of the drug Heptral® in patients with renal failure, in this regard, caution is advised when using the drug Heptral® in such patients.
Liver failure
The pharmacokinetics of ademetionine are similar in healthy volunteers and in patients with chronic liver disease.
Children
The use of the drug Heptral® in children is contraindicated (efficacy and safety have not been established).
Overdose
An overdose of Heptral® is unlikely. In case of an overdose, monitoring the patient and symptomatic therapy is recommended.
Special instructions
Given the tonic effect of the drug, it is not recommended to take it before bedtime. When using the drug Heptral® in patients with liver cirrhosis against the background of hyperazotemia, a 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.
There are reports of the transition of depression to hypomania or mania in patients taking ademetionin.
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, discontinuation of therapy is not required; in several cases, anxiety disappeared after a 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, in connection with other diseases or diet, for example, vegetarians), the content of vitamins in blood plasma should be monitored. If a deficiency is detected, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademethionine or simultaneous administration with ademethionine.
In immunological analysis, the use of ademetionine can contribute to the false determination of an indicator of high homocysteine ​​in the blood.
For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine the content of homocysteine.
There are reports of the transition of depression to hypomania or mania in patients taking ademetionin.
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, discontinuation of therapy is not required; in several cases, anxiety disappeared after a 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, in connection with other diseases or diet, for example, vegetarians), the content of vitamins in blood plasma should be monitored. If a deficiency is detected, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademethionine or simultaneous administration with ademethionine.
In immunological analysis, the use of ademetionine can contribute to the false determination of an indicator of high homocysteine ​​in the blood.
For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine the content of homocysteine.
Influence on the ability to drive a car and work with mechanisms
In some patients, dizziness may occur when taking Heptral®. It is not recommended to drive a car and work with mechanisms while taking the drug until the patient is confident that therapy does not affect the ability to engage in this type of activity.
Storage conditions
In a dark place at a temperature of 15 ° C to 25 ° C.
Keep out of the reach of children.
Keep out of the reach of children.
Shelf life
3 years. Do not use the drug after the expiration date.