Heptral injections: how to remove them from the body. Heptral: instructions for use tablets, injections
Country of origin
Italy Russia UNITED STATES FranceProduct group
Digestive tract and metabolismHepatoprotector. A drug with antidepressant activity
Release forms
- 10 - contour cell packaging (1) - cardboard boxes. 10 - contour cell packaging (2) - cardboard boxes. Bottles (5) complete with solvent (5 ml - amp. 5) - cardboard boxes.
Description of the dosage form
- Lyophilisate for the preparation of a solution for intravenous and intramuscular administration, white. Tablets, enteric-coated, almost white, oval, without dividing lines.
pharmachologic effect
Hepatoprotector, has antidepressant activity. It has choleretic and cholekinetic effects. It has detoxifying, regenerating, antioxidant, antifibrosing and neuroprotective properties. Replenishes ademetionine deficiency and stimulates its production in the body, primarily in the liver and brain. Participates in biological transmethylation reactions (methyl group donor) - the S-adenosyl-L-methionine molecule (ademetionine) donates a methyl group in methylation reactions of phospholipids of cell membranes, proteins, hormones, neurotransmitters; transsulfation - a precursor of cysteine, taurine, glutathione (provides a redox mechanism for cellular detoxification), acetylation coenzyme. 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 the processes of aminopropylation as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), 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 the synthesis of phosphatidylcholine 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. Effective for intralobular cholestasis (impaired synthesis and flow of bile). 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 facilitates their elimination by the kidneys, facilitates their passage through the hepatocyte membrane and excretion in the bile. In addition, sulfated bile acids protect liver cell membranes from the toxic effects of non-sulfated bile acids (present in high concentrations in hepatocytes during intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of skin itching and changes in biochemical parameters, incl. level of direct bilirubin, alkaline phosphatase activity, aminotransferases. The choleretic and hepatoprotective effect lasts up to 3 months after cessation of treatment. Shown to be effective in hepatopathies caused by hepatotoxic drugs. Prescribing the drug to patients with opioid addiction accompanied by liver damage leads to regression of clinical manifestations of withdrawal, improvement of the functional state of the liver and microsomal oxidation processes. Antidepressant activity appears gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. The drug is effective for recurrent endogenous and neurotic depression resistant to amitriptyline. Has the ability to interrupt relapses of depression. Prescribing the drug for osteoarthritis reduces the severity of pain, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.Pharmacokinetics
Absorption The tablets are coated with a special coating that dissolves only in the intestine, due to which ademetionine is released in the duodenum. After a single oral dose of 400 mg of the drug, Cmax of ademetionine in plasma is achieved after 2-6 hours and is 0.7 mg/l. The bioavailability of the drug when taken orally is 5%, when administered intramuscularly - 95%. Distribution: Binding to serum proteins is negligible. Penetrates through the BBB. Regardless of the route of administration, there is a significant increase in the concentration of ademetionine in the cerebrospinal fluid. Metabolism Biotransformed in the liver. Excretion T1/2 - 1.5 hours. Excreted by the kidneys.Special conditions
Considering the tonic effect of Heptral, it is not recommended to use it before bedtime. When prescribing Heptral to patients with liver cirrhosis due to hyperazotemia, systematic monitoring of the level of nitrogen in the blood is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum. The solution is prepared immediately before use; If the color of the lyophilized powder differs from the intended white color, you should refrain from using it.Compound
- ademetionine 1,4-butane disulfonate 760 mg, which is resp. ademetionine content 400 mg Solvent: L-lysine, sodium hydroxide, water for injection. ademetionine 1,4-butane disulfonate 760 mg, which corresponds to the content of ademetionine 400 mg Excipients: colloidal anhydrous silicon dioxide, sodium starch glycolate, magnesium stearate, microcrystalline cellulose. Shell composition: polymethacrylate, polyethylene glycol, talc, simethicone, polysorbate, purified water.
Heptral indications for use
- - chronic acalculous cholecystitis; - cholangitis; - intrahepatic cholestasis; - toxic liver damage of various etiologies (including alcohol, viral, drugs /antibiotics, antitumor drugs, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives/); - fatty liver degeneration; - chronic hepatitis; - cirrhosis of the liver; - encephalopathy, incl. associated with liver failure (including alcoholic); - depression (including secondary); - withdrawal syndrome (including alcoholic).
Heptral contraindications
- - I and II trimester of pregnancy; - lactation period (breastfeeding); - age up to 18 years; - hypersensitivity to the components of the drug.
Heptral dosage
- 400 mg
Heptral side effects
- The most common adverse reactions include nausea, abdominal pain and diarrhea. Below is a summary of the adverse reactions that were identified during clinical trials and post-marketing use of ademetionine both in tablets and injectable dosage form. From the immune system: hypersensitivity reactions, anaphylactoid or anaphylactic reactions (including skin hyperemia, shortness of breath, bronchospasm, back pain, discomfort in the chest, arterial hypotension, arterial hypertension, tachycardia, bradycardia). From the respiratory system: laryngeal edema. From the side of the legs: reactions at the injection site (very rarely with skin necrosis), Quincke's edema, sweating, skin reactions, allergic skin reactions (including rash, itching, urticaria, erythema). Infections and infestations: urinary tract infections. From the nervous system: dizziness, headache, paresthesia, anxiety, confusion, insomnia. From the cardiovascular system: hot flashes, phlebitis of superficial veins, cardiovascular disorders. From the digestive system: bloating, abdominal pain, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastrointestinal disorders, gastrointestinal bleeding, nausea, vomiting, hepatic colic, cirrhosis. From the musculoskeletal system", arthralgia, muscle spasms. Others: asthenia, chills, flu-like syndrome, malaise, peripheral edema, fever.
Drug interactions
There were no known drug interactions between Heptral® and other drugs.Overdose
There were no clinical cases of overdose.Storage conditions
- keep away from children
In this article you can read the instructions for use of the drug Heptral. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Heptral in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Analogues of Heptral in the presence of existing structural analogues. Use for the treatment of liver diseases in adults, children, as well as during pregnancy and lactation.
Heptral- hepatoprotector, has antidepressant activity. It has choleretic and cholekinetic effects. It has detoxifying, regenerating, antioxidant, antifibrosing and neuroprotective properties.
Replenishes the deficiency of ademetionine (the active ingredient of the drug Heptral) and stimulates its production in the body, primarily in the liver and brain. Participates in biological transmethylation reactions (methyl group donor) - the S-adenosyl-L-methionine molecule (ademetionine) donates a methyl group in methylation reactions of phospholipids of cell membranes, proteins, hormones, neurotransmitters; transsulfation - a precursor of cysteine, taurine, glutathione (provides a redox mechanism for cellular detoxification), acetylation coenzyme. 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 the processes of aminopropylation as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), 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 the synthesis of phosphatidylcholine 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. Effective for intralobular cholestasis (impaired synthesis and flow of bile). 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 facilitates their elimination by the kidneys, facilitates their passage through the hepatocyte membrane and excretion in the bile. In addition, sulfated bile acids protect liver cell membranes from the toxic effects of non-sulfated bile acids (present in high concentrations in hepatocytes during intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of skin itching and changes in biochemical parameters, incl. level of direct bilirubin, alkaline phosphatase activity, aminotransferases.
The choleretic and hepatoprotective effect lasts up to 3 months after cessation of treatment.
Shown to be effective in hepatopathies caused by hepatotoxic drugs.
Prescribing the drug to patients with opioid addiction accompanied by liver damage leads to regression of clinical manifestations of withdrawal, improvement of the functional state of the liver and microsomal oxidation processes.
Antidepressant activity appears gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. The drug is effective for recurrent endogenous and neurotic depression resistant to amitriptyline. Has the ability to interrupt relapses of depression.
Prescribing the drug for osteoarthritis reduces the severity of pain, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.
Pharmacokinetics
The tablets are coated with a special coating that dissolves only in the intestines, thanks to which ademetionine is released in the duodenum. Binding to serum proteins is negligible. Penetrates the blood-brain barrier. Regardless of the route of administration, there is a significant increase in the concentration of ademetionine in the cerebrospinal fluid. Biotransformed in the liver. Excreted by the kidneys.
Indications
- chronic acalculous cholecystitis;
- cholangitis;
- intrahepatic cholestasis;
- toxic liver damage of various etiologies (including alcohol, viral, drugs /antibiotics, antitumor drugs, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives/);
- fatty liver;
- chronic hepatitis;
- cirrhosis of the liver;
- encephalopathy, incl. associated with liver failure (including alcoholic);
- depression (including secondary);
- withdrawal syndrome (including alcohol).
Release forms
Tablets, coated, soluble in the intestine 400 mg.
Lyophilisate for the preparation of a solution for intravenous and intramuscular administration (injections in injection ampoules).
Instructions for use and dosage
Pills
The drug is prescribed orally in a daily dose of 800-1600 mg. The duration of maintenance therapy can average 2-4 weeks.
The tablets should be swallowed whole, without chewing, it is advisable to take them in the first half of the day, between meals.
Ampoules
Use intravenously or intramuscularly.
The lyophilisate must be dissolved in a specially supplied solvent immediately before administration. The remainder of the drug must be disposed of.
The drug must not be mixed with alkaline solutions and solutions containing calcium ions.
If the lyophilisate has a color other than almost white to white with a yellowish tint (due to a crack in the bottle or exposure to heat), the use of Heptral is not recommended.
When administered intravenously, Heptral is administered very slowly.
Intrahepatic cholestasis
The drug is administered in a dose of 400 mg per day to 800 mg per day (1-2 bottles per day) for 2 weeks.
Depression
The drug is administered in a dose of 400 mg per day to 800 mg per day (1-2 bottles per day) for 15-20 days.
If maintenance therapy is necessary, it is recommended to continue taking Heptral in tablet form at a dose of 800-1600 mg per day for 2-4 weeks.
Side effect
- gastralgia;
- dyspepsia;
- heartburn;
- allergic reactions.
Contraindications
- 1st and 2nd trimester of pregnancy;
- lactation period (breastfeeding);
- age under 18 years;
- hypersensitivity to the components of the drug.
Use during pregnancy and breastfeeding
Use in children
Contraindicated in children and adolescents under 18 years of age.
special instructions
Considering the tonic effect of Heptral, it is not recommended to use it before bedtime.
When prescribing Heptral to patients with liver cirrhosis due to hyperazotemia, systematic monitoring of the level of nitrogen in the blood is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.
The solution is prepared immediately before use; If the color of the lyophilized powder differs from the intended white color, you should refrain from using it.
Drug interactions
There were no known drug interactions between Heptral and other drugs.
Analogues of the drug Heptral
Structural analogues of the active substance:
- S-adenosyl-L-methionine disulfate p-toluenesulfonate;
- S-Adenosylmethionine;
- Ademethionine 1,4-butane disulfonate;
- Heptor;
- Heptor N.
If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.
Hepatoprotector
Active substance
Release form, composition and packaging
Lyophilisate for preparing a solution for intravenous and intramuscular administration from almost white to white with a yellowish tint; solvent - a transparent solution from colorless to light yellow; the reconstituted solution is a clear, colorless to yellow solution.
Solvent: L-lysine - 324.4 mg, sodium hydroxide - 11.5 mg, liquid water - up to 5 ml.
Colorless glass bottles type I (5) complete with solvent (amp. 5 ml 5 pcs.) - cardboard packs.
Colorless glass bottles type I (5) complete with solvent (amp. 5 ml 5 pcs.) - contour plastic cell packaging (1) - cardboard packs.
pharmachologic effect
Pharmacodynamics
Ademetionine belongs to the group of hepatoprotectors and also has antidepressant activity. It has choleretic and cholekinetic effects. It has detoxifying, regenerating, antioxidant, antifibrosing and neuroprotective properties.
Replenishes the deficiency of S-adenosyl-L-methionine (ademetionine) and stimulates its production in the body; it is found in all environments of the body. The highest concentration of ademetionine was observed in the liver and brain. Plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transsulfurization, transamination. In transmethylation reactions, ademetionine donates a methyl group for the synthesis of cell membrane phospholipids, neurotransmitters, nucleic acids, proteins, hormones, etc. In transsulfation reactions, ademetionine is a precursor of cysteine, taurine, glutathione (providing a redox mechanism of cellular detoxification), coenzyme A (included 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; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in the processes of aminopropylation as a precursor of polyamines - putrescine (stimulator of cell regeneration and proliferation of hepatocytes), spermidine and spermine, which are part of the structure of ribosomes, which reduces the risk of fibrosis.
Has a choleretic effect. Ademetionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases membrane fluidity and polarization. This improves the function of bile acid transport systems associated with hepatocyte membranes and promotes the passage of bile acids into the biliary tract. Effective for intralobular cholestasis (impaired synthesis and flow of bile). Ademetionine reduces the toxicity of bile acids in hepatocytes by conjugating and sulfating them. Conjugation with increases the solubility of bile acids and their removal from the hepatocyte. The process of sulfation of bile acids facilitates their elimination by the kidneys, facilitates their passage through the hepatocyte membrane and excretion in the bile. In addition, sulfated bile acids themselves additionally protect liver cell membranes from the toxic effects of non-sulfated bile acids (present in high concentrations in hepatocytes during 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, incl. concentrations of direct bilirubin, alkaline phosphatase activity, aminotransferases, etc. The choleretic and hepatoprotective effect lasts up to 3 months after cessation of treatment.
It has been shown to be effective against hepatopathies caused by various hepatotoxic drugs.
Antidepressant activity appears gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment.
Pharmacokinetics
Suction
Bioavailability after parenteral administration is 96%, plasma concentration reaches maximum values after 45 minutes.
Distribution
The connection with blood plasma proteins is insignificant, ≤ 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 formation, consumption and re-formation of ademetionine is called the ademetionine cycle. In the first step of this cycle, ademetionine-dependent methylases use ademetionine as a substrate to produce S-adenosylhomocysteine, which is then hydrolyzed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase. Homocysteine, in turn, undergoes a reverse transformation to by transfer of a methyl group from 5-methyltetrahydrofolate. Eventually, methionine can be converted to ademetionine, completing the cycle.
Removal
Half-life (T 1/2) - 1.5 hours. Excreted by the kidneys.
Indications
- intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
Fatty liver degeneration;
Chronic hepatitis;
Toxic liver damage of various etiologies, including alcohol, viral, drugs (antibiotics, antitumor, anti-tuberculosis drugs, tricyclic antidepressants, oral contraceptives);
Chronic acalculous cholecystitis;
Cholangitis;
Cirrhosis of the liver;
Encephalopathy, incl. associated with liver failure (including alcoholic);
- 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 disorders);
- bipolar disorders;
- age under 18 years (experience of medical use in children is limited);
- hypersensitivity to any of the components of the drug.
Carefully
Pregnancy (first trimester) and breastfeeding period (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 drugs and drugs containing tryptophan (see section "Drug Interactions").
Elderly age.
Kidney failure.
Dosage
Use intravenously and intramuscularly.
Before use, the lyophilisate for IM and IV 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 saline or 5% glucose solution and administered slowly over 1-2 hours.
The drug must not be mixed with alkaline solutions and solutions containing calcium ions.
If the lyophilisate has a color other than almost white to white with a yellowish tint (due to a crack in the bottle or exposure to heat), the drug is not recommended to be used.
Depression
The drug is administered in a dose of 400 mg/day to 800 mg/day (1-2 bottles/day) for 15-20 days.
Intrahepatic cholestasis
The drug is administered in a dose of 400 mg/day to 800 mg/day (1-2 bottles/day) for 2 weeks.
If maintenance therapy is necessary, it is recommended to continue taking Heptral in tablet form at a dose of 800-1600 mg/day for 2-4 weeks.
Therapy with Heptral can be started with intravenous or intramuscular administration followed by the use of Heptral in tablet form or immediately with the use of the drug 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 liver, kidney or cardiac dysfunction, other concomitant pathology or concomitant therapy with other drugs, the dose of Heptral in elderly patients should be selected with caution, starting the use of the drug from the lower limit of the dose range.
Kidney failure
There are limited clinical data on the use of Heptral in patients with renal failure; therefore, caution is recommended when using Heptral in this group of patients.
Liver failure
The pharmacokinetic parameters of ademetionine are similar in healthy volunteers and in patients with chronic liver diseases.
Children
The use of Heptral in children is contraindicated (efficacy and safety have not been established).
Side effects
The most common adverse reactions identified in clinical studies involving more than 2,100 patients were headache, nausea and diarrhea. Below are data on adverse reactions observed during clinical trials (n=2115) and during post-marketing use of ademetionine (“spontaneous” reports). All reactions are distributed according to organ systems and frequency of development: very often (≥1/10); often (≥1/100,<1/10); нечасто (≥1/1000, <1/100); редко (≥1/10 000, <1/1000); очень редко (<1/10 000).
| Frequency | Undesirable effects |
| From the immune system | |
| Infrequently | Hypersensitivity reactions Anaphylactoid or anaphylactic reactions (including skin hyperemia, shortness of breath, bronchospasm, back pain, discomfort in the chest, changes in blood pressure (hypotension, arterial hypertension) or pulse rate (tachycardia, bradycardia))* |
| Mental disorders | |
| Often | Anxiety Insomnia |
| Infrequently | Agitation Confusion |
| From the nervous system | |
| Often | Headache |
| Infrequently | Dizziness Paresthesia Dysgeusia* |
| From the side of blood vessels | |
| Infrequently | "Tides" Arterial hypotension Phlebitis |
| From the respiratory system, chest organs and mediastinum | |
| Infrequently | Laryngeal edema* |
| From the gastrointestinal tract | |
| Often | Abdominal pain Diarrhea Nausea |
| Infrequently | Dry mouth Dyspepsia Flatulence Gastrointestinal pain Gastrointestinal bleeding Gastrointestinal disorders Vomit |
| Rarely | Bloating Esophagitis |
| From the skin and subcutaneous tissues | |
| Often | Itchy skin |
| Infrequently | Increased sweating Angioedema* Allergic skin reactions (including rash, itching, urticaria, erythema)* |
| From the musculoskeletal system and connective tissue | |
| Infrequently | Arthralgia Muscle spasms |
| General and administration site disorders | |
| Infrequently | Asthenia Edema Fever Chills* Reactions at the injection site* Skin necrosis at the injection site* |
| Rarely | Malaise |
* Adverse effects identified during post-marketing use of ademetionine ("spontaneous" reports) that were not observed during clinical trials were classified as adverse effects with an incidence of "infrequent" based on the fact that the upper limit of the 95% confidence interval of the incidence estimate did not exceed 3/X, where X=2115 (total number of subjects observed in clinical studies).
Overdose
An overdose of Heptral is unlikely. In case of overdose, observation of the patient and symptomatic therapy are recommended.
Drug interactions
There were no known drug interactions between Heptral and other drugs.
There is a report of serotonin excess syndrome in a patient taking ademetionine and clomipramine. It is believed that such an interaction is possible and caution should be used when ademetionine is prescribed together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbal remedies and drugs containing tryptophan.
special instructions
Given the tonic effect of the drug, it is not recommended to use it before bedtime.
When using the drug Heptral in patients with liver cirrhosis against the background of hyperazotemia, systematic monitoring of nitrogen levels 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 ademetionine.
Patients with depression have an increased risk of suicide and other serious adverse events, therefore, during treatment with ademetionine, such patients should be closely monitored by a physician to evaluate and treat symptoms of depression. Patients should inform their physician if their symptoms of depression do not improve or worsen with ademetionine therapy.
There are also reports of sudden onset or worsening anxiety in patients taking ademetionine. In most cases, discontinuation of therapy is not required; in several cases, the state of anxiety disappeared after reducing the dose or discontinuing the drug.
Since cyanocobalamin deficiency can reduce the level 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, vegetarians), the content of vitamins in the blood plasma should be monitored. If deficiency is detected, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademetionine or simultaneous use with ademetionine.
In immunological analysis, the use of ademetionine may contribute to the false determination of high homocysteine levels in the blood. For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine homocysteine levels.
One bottle of Heptral lyophilisate for the preparation of a solution for intravenous and intramuscular administration, 400 mg/5 ml contains 6.61 mg of sodium, which is equivalent to the amount of sodium in 16.8 mg of table salt and is 0.3% of the recommended maximum daily sodium intake for an adult.
Impact on the ability to drive a car and operate machinery
Some patients may experience dizziness while taking Heptral. It is not recommended to drive a car or operate machinery while taking the drug until the patient is sure that the therapy does not affect the ability to engage in these types of activities.
Pregnancy and lactation
Clinical studies have shown that the use of ademetionine in the third trimester of pregnancy did not cause any undesirable effects.
The use of Heptral in the first trimester of pregnancy and during breastfeeding is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child.
For impaired renal function
Shelf life: 3 years. Do not use the drug after the expiration date.
Heptral instructions for use of the drug
Tradename: Heptral ®
International nonproprietary name: Ademetionine
Dosage form: Lyophilized powder for the preparation of a solution for intravenous and intramuscular administration of 500 mg, complete with a solvent of 5 ml.
Heptral 500 mg (Ademethionine) photo
Heptral instructions for use (injections in ampoules)
Ademetionine- a drug that has moderate antidepressant, stimulating and hepatoprotective properties. Actively penetrates the blood-brain barrier and stimulates the synthesis of dopamine.
The effectiveness of the drug for depression has been proven in a number of studies. The results of open-label and double-blind trials confirmed a statistically significant superiority of S-adenosylmethionine therapy compared to placebo and comparable efficacy to standard tricyclic antidepressants, as well as a favorable side effect profile.
Wikipedia
Composition and properties Heptral injections in ampoules
One bottle contains:
- active substance: ademetionine 1,4-butane disulfonate 949 mg (equivalent to 500 mg of ademetionine cation);
- excipients: water for injection, nitrogen;
One ampoule with solvent contains active substances: L-lysine 428.0 mg, sodium hydroxide 14.4 mg excipient - water for injection.
Description
- Lyophilized powder- lyophilized mass from white to yellowish color, free from foreign particles;
- Solvent - transparent liquid from colorless to light yellow;
- Prepared drug solution- a clear solution from colorless to yellow without visible sediment.
Pharmacotherapeutic group: Other drugs for the treatment of gastrointestinal diseases and metabolic disorders. Amino acids and their derivatives. Ademetionine
ATX code: A16AA02
Pharmacological properties
Pharmacokinetics
Absorption
In humans, after intravenous administration, the pharmacokinetic profile of ademetionine is biexpotential with a rapid phase of tissue distribution and clearance with a half-life of approximately 1.5 hours.
Absorption after intramuscular administration is 96%, maximum plasma concentrations are reached after 45 minutes. after use.
After a single oral administration of enteric ademetionine tablets in doses of 400 to 1000 mg, the maximum plasma concentrations achieved are dose-dependent and range from 0.5 to 1 mg/l after 3-5 hours.
Bioavailability after oral administration is increased if ademetionine is administered on an empty stomach.
Plasma concentrations decrease to baseline values within 24 hours.
Distribution
The volume of distribution is 0.41 and 0.44 l/kg for doses of ademetionine 100 mg and 500 mg, respectively.
Binding to serum proteins is insignificant and amounts to ≤5%.
Metabolism
The process of ademetionine metabolism is cyclical and is called the ademetionine cycle.
In the first step of this cycle, ademetionine-dependent methylase uses ademetionine as a substrate to produce 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.
Ultimately, methionine can be converted to ademetionine, completing the cycle.
Removal
In radiolabeled clearance studies with oral administration of radiolabeled (methyl 14 C) ademetionine in healthy volunteers, urinary radioactive excretion was 15.5 ± 1.5% at 48 hours and fecal excretion was 23.5 ± 1.5% at 48 hours. 3.5% after 72 hours.
Pharmacodynamics
Heptral ® (active substance - S-adenosyl-L-methionine (ademetionine)) is a natural amino acid that is present in all tissues and fluids of the body.
Heptral (ademetionine) primarily acts as a coenzyme and methyl group donor in many transmethylation reactions.
The transfer of methyl groups (transmethylation) of ademetionine is the basis for the construction of the phospholipid membrane of cells and plays a role in membrane fluidity.
Heptral (ademetionine) is able to penetrate the blood-brain barrier.
High concentrations of Heptral (ademetionine) affect transmethylation processes, which are very important in brain tissue, due to their effect on the metabolism of catecholamines (dopamine, adrenaline, norepinephrine), indoamines (serotonin, melatonin) and histamine.
Heptral (ademetionine) is also a precursor of biochemical thiol compounds (cysteine, taurine, glutathione, coenzyme A, etc.) in transsulfurization reactions. Glutathione, a powerful antioxidant, is an important component for liver detoxification.
Heptral increases glutathione levels in patients with liver damage of both alcoholic and non-alcoholic origin.
Heptral instructions for use
Each 400 mg bottle of lyophilized powder contains:
active ingredient: ademetionine 1,4-butane disulfonate - 760 mg, which corresponds to 400 mg of ademetionine cation.
L-lysine - 342.4 mg, sodium hydroxide - 11.5 mg, water for injection up to 5 ml.
Each 500 mg bottle of lyophilized powder contains:
active ingredient: ademetionine 1,4-butane disulfonate - 949 mg, which corresponds to 500 mg of ademetionine cation.
Each solvent ampoule contains:
L-lysine - 428 mg, sodium hydroxide - 14.4 mg, water for injection up to 5 ml.
Each 400 mg tablet contains:
active ingredient: ademetionine 1,4-butane disulfonate - 760 mg, which corresponds to 400 mg of ademetionine cation;
excipients: anhydrous colloidal silicon dioxide - 4.4 mg, microcrystalline cellulose - 93.6 mg, sodium starch glycolate (type A) - 17.6 mg, magnesium stearate - 4.4 mg;
tablet shell: methacrylic acid and ethyl acrylate copolymer - 27.6 mg, macrogol-6000 - 8.07 mg, polysorbate-80 - 0.44 mg, simethicone (30% emulsion) - 0.13 mg, sodium hydroxide - 0.36 mg, talc - 18.4 mg.
Each 500 mg tablet contains:
active ingredient: ademetionine 1,4-butane disulfonate - 949 mg, which corresponds to 500 mg of ademetionine cation;
excipients: anhydrous colloidal silicon dioxide - 5.50 mg, microcrystalline cellulose - 118 mg, sodium starch glycolate (type A) - 22 mg, magnesium stearate - 5.50 mg;
tablet shell: methacrylic acid and ethyl acrylate copolymer - 32.63 mg, macrogol-6000 - 9.56 mg, polysorbate-80 - 0.52 mg, simethicone (30% emulsion) - 0.40 mg, sodium hydroxide - 0.44 mg, talc - 21.77 mg.
Description
Lyophilized powder is a lyophilized mass from almost white to yellowish color, free from foreign particles.
Solvent is a transparent liquid from colorless to light yellow, free from foreign particles.
The prepared solution of the drug is a transparent solution without visible particles, from colorless to yellow.
Film-coated tablets are white to yellowish in color, oval in shape, without cracks, cap effect and swelling.
ATX code: A16AA02
Pharmacotherapeutic group:
Amino acids and their derivatives.
Pharmacological properties:
Pharmacodynamics
S-adenosyl-L-methionine (ademethionine) is a naturally occurring amino acid present in virtually all tissues and fluids of the body. Ademetionine is mainly involved as a coenzyme and methyl group donor in transmethylation reactions - the most important metabolic process in humans and animals. The process of methyl group transfer is also important for the formation of the phospholipid bilayer of cell membranes, and contributes to membrane plasticity. Ademetionine can cross the blood-brain barrier, and ademetionine-mediated transmethylation plays a critical role in the formation of neurotransmitters in the central nervous system, including catecholamines (dopamine, norepinephrine, epinephrine), serotonin, melatonin and histamine.
Ademetionine is also a precursor in the process of formation of physiologically active sulfated compounds (cysteine, taurine, glutathione, coenzyme A, etc.) through transsulfuration. Glutathione, the liver's most active antioxidant, plays an important role in detoxification processes. Ademetionine increases glutathione levels in the liver in patients with liver diseases of alcoholic and non-alcoholic etiology. Substances such as folate and vitamin B12 play an important role in the metabolism and replenishment of ademetionine.
Pharmacokinetics
Suction
The pharmacokinetic profile of ademetionine, following intravenous administration in humans, is biphasic, consisting of a rapid tissue distribution phase and a terminal elimination phase, with a half-life of approximately 1.5 hours. After intramuscular administration, almost complete absorption of ademetionine is observed (96%); Maximum concentrations of ademetionine in blood plasma are reached after approximately 45 minutes. Peak plasma concentrations following oral administration are dose-related, with peak plasma concentrations of 0.5 to 1 mg/L 3 to 5 hours after a single dose of 400 to 1000 mg. Plasma concentrations decreased to baseline levels within 24 hours. The bioavailability of the drug increases when taken on an empty stomach.
Distribution
The volume of distribution was 0.41 and 0.44 l/kg when using ademetionine in doses of 100 mg and 500 mg, respectively. The degree of binding to plasma proteins is insignificant and is ≤ 5%.
Metabolism
The reactions of synthesis, utilization and resynthesis of ademetionine are called the ademetionine cycle. At the first stage of this cycle, ademetionine acts as a substrate for ademetionine-dependent methylases that form S-adenosyl-homocysteine. S-adenosyl-homocysteine is hydrolyzed to homocysteine and adenosine by S-adenosyl-homocysteine hydrolase. Homocysteine is then converted back to methionine by transfer of the methyl group from 5-methyltetrahydrofolate. Finally, methionine is converted back to ademetionine, completing the cycle.
Removal
In radiolabeled clearance studies with oral administration of radiolabeled (methyl 14C) ademetionine in healthy volunteers, urinary excretion of the radioactive substance was 15.5 ± 1.5 % after 48 hours and fecal excretion was 23.5 ± 3.5% after 72 hours.
Indications for medical use
Heptral® is indicated for the treatment of adults with:
Intrahepatic cholestasis in precirrhotic and cirrhotic conditions; intrahepatic cholestasis during pregnancy; symptoms of depression.
Directions for use and dosage
Treating Depressive Symptoms
Treatment with the drug can be started with parenteral bb eden And I followed by transition to oral administration, or can be started immediately with oral administration.
Initial therapy:
Intravenous or intramuscular administration: 1 bottle (400 mg) per day for 15-20 days.
Intrahepatic cholestasis
Treatment with the drug can be started with parenteral administration followed by oral administration, or it can be started immediately with oral administration.
Initial therapy:
Intravenous or intramuscular administration: The recommended dose is 5-12 mg/kg/day intravenously or intramuscularly for the first 2 weeks. The usual starting dose is 500 mg/day, the daily dose should not exceed 800 mg. Oral administration: the recommended dose is 10-25 mg/kg/day. The usual starting dose is 800 mg/day, the total daily dose should not exceed 1600 mg.
Maintenance therapy:
Oral intake: 800-1600 mg/day.
The duration of therapy depends on the severity and course of the disease and is determined by the doctor individually.
Use in children
The effectiveness and safety of ademetionine in children (under 18 years of age) has not been established.
Usageelderly
Clinical studies of ademetionine did not include a sufficient number of patients aged 65 years and older to determine possible differences in the effectiveness of the drug in patients of this age group and in younger patients.
Clinical experience with the drug has not revealed any differences in its effectiveness in elderly patients and younger patients. In general, given the high likelihood of existing hepatic, renal or cardiac dysfunction, other concomitant pathology, or concomitant therapy with other drugs, the dose of the drug in elderly patients should be adjusted with caution, starting the drug at the lower end of the dosage range.
Use in patients with renal failure
Studies have not been conducted in patients with renal failure; therefore, caution is recommended when using ademetionine in such patients.
Use in patients with liver failure
The pharmacokinetic parameters of ademetionine are similar in healthy volunteers and in patients with chronic liver diseases.
Powderlyophilized:
The lyophilized powder must be dissolved in the supplied solvent immediately before administration. The remainder of the drug must be disposed of. Ademetionine should not be mixed with alkaline solutions and solutions containing calcium ions.
If the lyophilized powder has a color other than almost white to yellowish (due to a crack in the bottle or exposure to heat), the drug is not recommended for use.
Intravenous administration of ademetionine should be carried out very slowly.
Pills :
Ademetionine tablets should be swallowed whole without chewing.
For better absorption of the active component and to achieve maximum therapeutic effect, ademetionine tablets should not be taken with food.
Ademetionine tablets should be removed from the blister immediately before ingestion. If the tablets have a color other than white to white with a yellowish tint (due to leakage of aluminum foil), the drug is not recommended to be used.
Adverse reactions
In controlled, open-label clinical studies lasting up to two years, ademetionine was studied in 2,434 patients, of whom 1,983 were prescribed the drug for liver disease and 817 for depression.
The table presents information based on an analysis of data from 1667 patients treated with ademetionine in 22 clinical studies, of which a total of 188 adverse reactions were reported in 121 (7.2%) patients. The most common adverse reactions were nausea, abdominal pain and diarrhea. It was not always possible to identify the connection between an adverse event and the use of the drug.
Adverse reactions observed during post-registration use of the drug. Immune system disorders
Hypersensitivity, anaphylactoid reactions or anaphylactic reactions (in particular, hot flashes, shortness of breath, bronchospasm, back pain, chest discomfort, changes in blood pressure (hypotension, hypertension) or pulse rate (tachycardia, bradycardia).
Mental disorders
Anxiety.
Respiratory, thoracic and mediastinal disorders
Swelling of the larynx.
Skin and subcutaneous tissue disorders
Reactions at the injection site (very rarely with skin necrosis), Quincke's edema, allergic skin reactions (in particular, rash, itching, urticaria, erythema).
If any adverse reactions occur, including those not listed in this instruction, you must stop taking the medicine and consult a doctor.
Contraindications
The use of ademetionine is contraindicated in patients with genetic disorders that affect the methionine cycle and/or cause homocystinuria and/or hyperhomocysteinemia (for example, cystathionine beta synthetase deficiency, impaired metabolism of vitamin B12).
The use of ademetionine is contraindicated in patients with known hypersensitivity to the active component or to any of the auxiliary components of the drug.
Precautions for medical use
Intravenous administration of ademetionine should be carried out very slowly (see section “Method of administration and dosage”).
When taking ademetionine orally, plasma ammonia concentrations should be monitored in patients with cirrhosis and precirrhotic conditions with hyperammonemia.
Because vitamin B12 and folic acid deficiencies can lead to decreased ademetionine levels, routine blood tests should be performed in patients at risk (with anemia, liver disease, pregnancy, potential for vitamin deficiency, due to other diseases or diet, such as vegetarians). assessment of vitamin content in plasma. If deficiency is detected, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademetionine or simultaneous use with ademetionine. (see section “Pharmacological properties” - Metabolism).
Some patients may experience dizziness when using ademetionine. Patients should be aware of the need to refrain from driving vehicles or operating machinery during treatment with the drug, up to reasonable confirmation that ademetionine therapy does not impair their ability to engage in such activities (see section "Effects on the ability to drive vehicles and machinery).
Risk of suicide (in patients with symptoms of depression).
Depression is associated with an increased risk of suicidal ideation and suicide. This risk persists until stable remission. Improvement may occur after several weeks of treatment for depression. Patients should be closely monitored until improvement develops. Based on current clinical experience, the risk of suicide may increase in the early stages of treatment.
Patients with a history of suicidal behavior or those who experience suicidal thoughts before treatment should be closely monitored during treatment. A meta-analysis of clinical trials for the treatment of mental disorders showed that the use of antidepressants compared with placebo in patients under 25 years of age is associated with an increased risk of suicidal behavior. When prescribing antidepressants, careful monitoring of patients is necessary, especially in the initial stages of treatment and after dose changes. Patients (as well as those caring for the patient) should be warned about the need for constant monitoring and the need to immediately inform the attending physician if their symptoms of depression do not improve or worsen during treatment with ademetionine, as well as in the event of changes in behavior, the appearance of suicidal thoughts.
There have been reports of cases of patients developing, during treatment with ademetionine, a transition from depression to hypomania or mania.
There is one literature publication about serotonin syndrome in a patient taking ademetionine and clomipramine. Although possible interactions are hypothetical, caution is recommended when coadministering ademetionine with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), herbs, and drugs containing tryptophan (see Interactions with Other Drugs section). .
The effectiveness of ademetionine in the treatment of depression has been studied in short-term clinical studies (lasting 3-6 weeks). The effectiveness of ademetionine in treating depression over a longer period of time is unknown. There are many medications available to treat depression, and patients should consult their doctor to determine the best treatment. Patients should be aware of the need to inform their doctor if their symptoms of depression do not improve or worsen during treatment with ademetionine.
Patients with depression are at increased risk of suicide and other serious adverse events, and such patients should be closely monitored by a psychiatrist during treatment with ademetionine to ensure adequate assessment and treatment of depressive symptoms.
Cases of sudden onset or worsening of anxiety have been reported in patients treated with ademetionine. In most cases, interruption of therapy was not required. In isolated cases, anxiety disappeared after reducing the dose of the drug or stopping therapy.
Influence on determination results homocysteine immunological methods.
When taking ademetionine, a false increase in the level of homocysteine in the blood plasma may be observed, since ademetionine affects the results of homocysteine determination by immunological analysis. Thus, in patients receiving treatment with ademetionine, it is recommended to use non-immunological methods to determine plasma homocysteine levels.
Overdose
An overdose of ademetionine is unlikely. In case of overdose, a physician should contact a local poison control center. In general, in case of overdose, patient monitoring and symptomatic therapy are recommended.
Interaction with other drugs
Serotonin syndrome has been reported in a patient taking ademetionine and clomipramine. Therefore, although the possible interaction is hypothetical, caution is recommended when coadministering ademetionine with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), herbs, and drugs containing tryptophan (see Medical Precautions). application").
Use during pregnancy and breastfeeding
Pregnancy
The use of therapeutic doses of ademetionine in women in the last trimester of pregnancy did not lead to the development of any adverse effects. The use of ademetionine in the first trimester of pregnancy is allowed only if absolutely necessary.
Breastfeeding period
The use of ademetionine during breastfeeding is allowed only if the expected benefit to the mother outweighs the potential risk to the child.
Impact on the ability to drive vehicles and machinery
Some patients may experience dizziness when using ademetionine. Patients should be made aware of the need to refrain from driving vehicles or operating machinery during treatment with the drug, until it has been reasonably verified that ademetionine therapy does not impair their ability to engage in these types of activities (see section “Medical Precautions”). application").
Registration Certificate Holder:
Abbott Laboratories GmbH,
Freundallee 9A,
30173 Hannover, Germany.
Manufacturers:
Enteric-coated tablets:
AbbVi S.r.L.,
S.R. 148 Pontina, km 52,
Lyophilizedpowder:
Hospira S.p.A.,
Famar Legl, BP 103 st. de L'Isle,
28380 Saint-Rémy sur Havre, France.
Solvent:
Hospira S.p.A.,
Via Fozze Ardeatine 2, 20060 Liscate, Italy or
Famar S.A.,
Alimos Plant, st. Ag. Dimitriou 63, 17456 Alimos Athens, Greece.
Claims regarding the quality of the medicinal product should be sent to the following address: Representative office of Abbott Laboratories S.A. JSC (Swiss Confederation), Republic of Belarus, 220073 Minsk, 1st Zagorodny lane, 20, office 1503, tel./fax: +375 17 256 7920, e-mail: .
You can also report an adverse event when using a drug or a quality complaint to Abbott by calling +380 44 498 6080 (24 hours a day).
