ademethionine | Heptral bottles of 400 mg, 5 pcs.
Special Price
$43.24
Regular Price
$56.00
In stock
SKU
BID478119
Latin name
HEPTRAL
HEPTRAL
Latin name
HEPTRAL
Release form
Lyophilisate for solution for intravenous and intramuscular administration.
760 mg of lyophilisate in a type I clear glass bottle, sealed with a chlorobutyl stopper with an aluminum cap with a plastic cap. 5 ml solvent in ampoules of type I glass with a break point. 5 vials and 5 ampoules in a cardboard box along with instructions for medical use.
5 vials and 5 ampoules in a plastic blister strip packaging coated with aluminum foil.
1 contour blister pack in a cardboard box along with instructions for medical use.
Packaging
Vials (5) complete with solvent (5 ml - amp. 5 pcs.) - packs of cardboard.
Pharmacological action
Pharmacotherapeutic group
Other drugs for the gastrointestinal tract and metabolism, amino acids and their derivatives
ATX code
A16AA02
Pharmacological properties of
Pharmacodynamics
Ademethionine belongs to the group of hepatoprotectors and also has antidepressant activity. It has a choleretic and cholekinetic effect, has detoxification, regenerating, antioxidant, antifibrosing and neuroprotective properties.
Replenishes 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, and others. In the transulfurization reactions, ademetionine 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 the content of methionine in the serum, 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 proliferation of hepatocytes), 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 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 hepatocytes and excretion with bile.
Other than that, 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 lasts up to 3 months after treatment is discontinued. 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 treatment showed the effect of ademetionine treatment in reducing 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 at the same time achieved a positive response from symptoms of increased fatigue. Moreover, in patients with alcoholic liver disease and non-alcoholic fatty liver disease with an achieved response to ademetionine treatment with 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.
Pharmacokinetics of
Tablets are coated with a film coating that dissolves only in the intestine, so that ademethionine 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 are 0.5-1 mg / l 3-5 hours after a single oral dose of 400 to 1000 mg. Cmax of ademethionine in plasma is reduced to baseline within 24 hours.
Distribution of
Communication with blood plasma proteins is negligible, <5%.
Penetrates the blood-brain barrier. There is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.
Metabolism
Metabolized in the liver. The process of the formation, expenditure, and re-formation of ademetionine is called the ademethionine cycle. At the first stage of this cycle, ademethionine-dependent methylases use ademethionine as a substrate for the production of S-adenosylhomocysteine, which is then hydrolyzed to homocysteine and adenosine using S-adenosylhomocysteine hydralase. Homocysteine, in turn, undergoes a reverse transformation to methionine by transferring the methyl group from 5-methyltetrahydrofolate. As a result, methionine can be converted to ademethionine, completing the cycle.
Excretion
The elimination half-life (T ) is 1.5 hours. It is excreted by the kidneys. In studies in healthy volunteers, ingestion of labeled (methyl 14C) S-adenosyl-L-methionine in the urine revealed 15.5 ± 1.5% of radioactivity after 48 hours, and in feces - 23.5 ± 3.5% of radioactivity after 72 hours. Thus, about 60% was deposited.
Indications
Intrahepatic cholestasis in precirrhotic and cirrhotic conditions, which can be observed in the following diseases: fatty liver disease
chronic hepatitis
toxic liver lesions of various etiologies, including alcoholic, viral, and medicinal (antitumor, anti-tuberculosis and anti-tuberculosis drugs, tricyclic antidepressants, oral contraceptives)
chronic stoneless cholecystritis . 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, metabolic disorder of cyanocobalamin)
Hypersensitivity to any of the components of the drug
Age up to 18 years (medical experience in children is limited)
Bipolar disorder.
With caution
Pregnancy (I trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother outweighs the potential risk to the fetus or baby).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), as well as herbal and tryptophan-containing drugs (see section “Interaction with other drugs”).
Old age.
Renal failure.
Use in pregnancy and lactation
In clinical studies, it was shown that the use of ademetionine in the III trimester of pregnancy did not cause any undesirable effects.
The use of the drug HeptralВ® in pregnant women in the I and II trimesters, as well as during breastfeeding, is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child.
Composition
Bottle with lyophilisate contains:
Active ingredient:
ademetionine 1,4-butanedisulfonate 760 mg (corresponding to 400 mg of ademetionine ion).
Ampoule with solvent contains:
Excipients:
L-lysine 342.4 mg
sodium hydroxide 11.5 mg
water for injection up to 5 ml.
Dosage and Administration
Intravenously and intramuscularly.
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions with
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions with
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions withholding calcium ions.
If the lyophilisate has a color other than almost white to white with a yellowish tint (due to a crack in the vial or exposure to heat), Heptral® is not recommended.
Initial therapy:
The recommended dose is 5-12 mg / kg / day intravenously or intramuscularly.
Depression
From 400 mg / day to 800 mg / day (1-2 vials per day) for 15-20 days.
Intrahepatic cholestasis
From 400 mg / day to 800 mg / day (1-2 bottles per day) for 2 weeks.
If necessary, maintenance therapy is recommended to continue taking Heptral® in the form of tablets at a dose of 800-1600 mg / day for 2-4 weeks.
Heptral® therapy can be started with intravenous or intramuscular administration followed by the use of Heptral® in tablet form or immediately with the use of Heptral® in tablet form.
Elderly patients
Clinical experience with the use of the drug Heptral® did not reveal any differences in its effectiveness in elderly patients and younger patients. However, given the high likelihood of existing impaired liver, kidney, or heart function, other concomitant pathologies, 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, and therefore caution is advised when using the drug Heptral® in such patients.
Hepatic insufficiency
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).
Side effects of the digestive system: often - nausea, abdominal pain, diarrhea rarely - vomiting, dry mouth, esophagitis, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, liver 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 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 are very rare - Quincke's edema, laryngeal edema.
Other: rarely - hot flashes, superficial phlebitis, asthenia, chills, flu-like symptoms, weakness, peripheral edema, hyperthermia.
Drug interaction
No known interactions with other drugs have been observed.
There is a report of a syndrome of excess serotonin in a patient taking ademethionine and clomipramine.
It is believed that such an interaction is possible and should be administered with caution to ademethionine, together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), and herbs and preparations containing tryptophan.
Overdose
Overdose with Heptral® is unlikely.
In case of overdose, monitoring of the patient and carrying out of symptomatic therapy is recommended.
Storage conditions
In the dark place at a temperature of 15 РC to 25 РC.
Keep out of the reach of children.
Expiration
3 years.
pharmacy prescription
dosage form
dosage form
injection and infusion
HEPTRAL
Release form
Lyophilisate for solution for intravenous and intramuscular administration.
760 mg of lyophilisate in a type I clear glass bottle, sealed with a chlorobutyl stopper with an aluminum cap with a plastic cap. 5 ml solvent in ampoules of type I glass with a break point. 5 vials and 5 ampoules in a cardboard box along with instructions for medical use.
5 vials and 5 ampoules in a plastic blister strip packaging coated with aluminum foil.
1 contour blister pack in a cardboard box along with instructions for medical use.
Packaging
Vials (5) complete with solvent (5 ml - amp. 5 pcs.) - packs of cardboard.
Pharmacological action
Pharmacotherapeutic group
Other drugs for the gastrointestinal tract and metabolism, amino acids and their derivatives
ATX code
A16AA02
Pharmacological properties of
Pharmacodynamics
Ademethionine belongs to the group of hepatoprotectors and also has antidepressant activity. It has a choleretic and cholekinetic effect, has detoxification, regenerating, antioxidant, antifibrosing and neuroprotective properties.
Replenishes 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, and others. In the transulfurization reactions, ademetionine 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 the content of methionine in the serum, 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 proliferation of hepatocytes), 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 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 hepatocytes and excretion with bile.
Other than that, 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 lasts up to 3 months after treatment is discontinued. 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 treatment showed the effect of ademetionine treatment in reducing 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 at the same time achieved a positive response from symptoms of increased fatigue. Moreover, in patients with alcoholic liver disease and non-alcoholic fatty liver disease with an achieved response to ademetionine treatment with 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.
Pharmacokinetics of
Tablets are coated with a film coating that dissolves only in the intestine, so that ademethionine 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 are 0.5-1 mg / l 3-5 hours after a single oral dose of 400 to 1000 mg. Cmax of ademethionine in plasma is reduced to baseline within 24 hours.
Distribution of
Communication with blood plasma proteins is negligible, <5%.
Penetrates the blood-brain barrier. There is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.
Metabolism
Metabolized in the liver. The process of the formation, expenditure, and re-formation of ademetionine is called the ademethionine cycle. At the first stage of this cycle, ademethionine-dependent methylases use ademethionine as a substrate for the production of S-adenosylhomocysteine, which is then hydrolyzed to homocysteine and adenosine using S-adenosylhomocysteine hydralase. Homocysteine, in turn, undergoes a reverse transformation to methionine by transferring the methyl group from 5-methyltetrahydrofolate. As a result, methionine can be converted to ademethionine, completing the cycle.
Excretion
The elimination half-life (T ) is 1.5 hours. It is excreted by the kidneys. In studies in healthy volunteers, ingestion of labeled (methyl 14C) S-adenosyl-L-methionine in the urine revealed 15.5 ± 1.5% of radioactivity after 48 hours, and in feces - 23.5 ± 3.5% of radioactivity after 72 hours. Thus, about 60% was deposited.
Indications
Intrahepatic cholestasis in precirrhotic and cirrhotic conditions, which can be observed in the following diseases: fatty liver disease
chronic hepatitis
toxic liver lesions of various etiologies, including alcoholic, viral, and medicinal (antitumor, anti-tuberculosis and anti-tuberculosis drugs, tricyclic antidepressants, oral contraceptives)
chronic stoneless cholecystritis . 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, metabolic disorder of cyanocobalamin)
Hypersensitivity to any of the components of the drug
Age up to 18 years (medical experience in children is limited)
Bipolar disorder.
With caution
Pregnancy (I trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother outweighs the potential risk to the fetus or baby).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), as well as herbal and tryptophan-containing drugs (see section “Interaction with other drugs”).
Old age.
Renal failure.
Use in pregnancy and lactation
In clinical studies, it was shown that the use of ademetionine in the III trimester of pregnancy did not cause any undesirable effects.
The use of the drug HeptralВ® in pregnant women in the I and II trimesters, as well as during breastfeeding, is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child.
Composition
Bottle with lyophilisate contains:
Active ingredient:
ademetionine 1,4-butanedisulfonate 760 mg (corresponding to 400 mg of ademetionine ion).
Ampoule with solvent contains:
Excipients:
L-lysine 342.4 mg
sodium hydroxide 11.5 mg
water for injection up to 5 ml.
Dosage and Administration
Intravenously and intramuscularly.
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions with
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions with
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The remainder of the drug must be disposed of. The appropriate dose of the drug for intravenous administration should then be dissolved in 250 ml of physiological saline or 5% glucose solution and injected slowly for 1-2 hours.
The drug should not be mixed with alkaline solutions and solutions withholding calcium ions.
If the lyophilisate has a color other than almost white to white with a yellowish tint (due to a crack in the vial or exposure to heat), Heptral® is not recommended.
Initial therapy:
The recommended dose is 5-12 mg / kg / day intravenously or intramuscularly.
Depression
From 400 mg / day to 800 mg / day (1-2 vials per day) for 15-20 days.
Intrahepatic cholestasis
From 400 mg / day to 800 mg / day (1-2 bottles per day) for 2 weeks.
If necessary, maintenance therapy is recommended to continue taking Heptral® in the form of tablets at a dose of 800-1600 mg / day for 2-4 weeks.
Heptral® therapy can be started with intravenous or intramuscular administration followed by the use of Heptral® in tablet form or immediately with the use of Heptral® in tablet form.
Elderly patients
Clinical experience with the use of the drug Heptral® did not reveal any differences in its effectiveness in elderly patients and younger patients. However, given the high likelihood of existing impaired liver, kidney, or heart function, other concomitant pathologies, 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, and therefore caution is advised when using the drug Heptral® in such patients.
Hepatic insufficiency
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).
Side effects of the digestive system: often - nausea, abdominal pain, diarrhea rarely - vomiting, dry mouth, esophagitis, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, liver 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 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 are very rare - Quincke's edema, laryngeal edema.
Other: rarely - hot flashes, superficial phlebitis, asthenia, chills, flu-like symptoms, weakness, peripheral edema, hyperthermia.
Drug interaction
No known interactions with other drugs have been observed.
There is a report of a syndrome of excess serotonin in a patient taking ademethionine and clomipramine.
It is believed that such an interaction is possible and should be administered with caution to ademethionine, together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), and herbs and preparations containing tryptophan.
Overdose
Overdose with Heptral® is unlikely.
In case of overdose, monitoring of the patient and carrying out of symptomatic therapy is recommended.
Storage conditions
In the dark place at a temperature of 15 РC to 25 РC.
Keep out of the reach of children.
Expiration
3 years.
pharmacy prescription
dosage form
dosage form
injection and infusion
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