Heptral: average price 1650.60 rub.
Name of the drug: Heptral
Heptral is a medicine intended to cleanse and restore the liver, while also having antidepressant activity.
The photo shows the drug Heptral
- Latin name: Heptral
- ATX code: A16AA02
- Active substance: Ademetionine
- Manufacturer: Famar L'Aigle, France
Compound
Composition of tablets:
- 400 mg ademetionine (INN), MCC, silicon dioxide (in colloidal form);
- Na-carboxymethyl starch (type A);
- Mg stearate.
Enteric coating:
- ethyl acrylate and methacrylic acid copolymer (1:1);
- 30% simethicone emulsion;
- talc;
- macrogol 6000;
- polysorbate 80;
- Na hydroxide;
- water.
Dosage of ademetionine in one bottle of lyophilisate- 400 mg.
The solvent ampoule contains:
- L-lysine,
- Na hydroxide,
- water d/i.
Dosage form
- lyophilisate for the preparation of solution for intravenous and intramuscular injection;
- Enteric-coated tablets.
pharmachologic effect
- Choleretic;
- detoxifying;
- hepato- and neuroprotective;
- cholekinetic;
- antioxidant;
- antidepressant.
Pharmacodynamics
Ademetionine belongs to the group of hepatoprotectors, which has antidepressant activity. It has choleretic and cholekinetic effects, 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;
- transsulfation;
- transamination.
In transmethylation reactions, ademetionine donates a methyl group for the synthesis of phospholipids cell membranes, neurotransmitters, nucleic acids, proteins, hormones, etc. In transsulfation reactions, ademetionine is a precursor of cysteine, taurine, glutathione (providing a redox mechanism for cellular detoxification), acetylation coenzyme (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 plasma; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation reactions as a precursor of polyamines - putrescine (stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure, 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 transport systems associated with hepatocyte membranes bile acids and promotes the passage of bile acids into the biliary system. Effective for intrahepatic (intralobular and interlobular) variants of cholestasis (impaired synthesis and flow of bile). Ademetionine 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 the hepatocyte. The process of sulfation of bile acids facilitates their elimination by the kidneys, facilitates their passage through the hepatocyte membrane and excretion with 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 diseases liver (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, ademetionine reduces the severity of skin itching and changes in biochemical parameters, incl. level 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. Prescription to patients with opioid addiction accompanied by liver damage leads to regression clinical manifestations abstinence, improvement functional state 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. Effective for recurrent endogenous and neurotic depressions resistant to amitriptyline. Has the ability to interrupt relapses of depression.
Prescription for osteoarthritis reduces the severity pain syndrome, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.
Pharmacokinetics
- Bioavailability after parenteral administration is 96%, plasma concentration reaches maximum values after 45 minutes.
- Metabolized in the liver.
- Communication with blood plasma proteins is insignificant.
- Penetrates the blood-brain barrier.
- There is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.
- Half-life (T1/2) - 1.5 hours.
- Excreted by the kidneys.
Indications for use of Heptral
1. Intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
- fatty liver;
- chronic hepatitis;
- toxic liver damage of various etiologies, including alcohol, viral, drugs (antibiotics, antitumor, antituberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives);
- chronic acalculous cholecystitis;
- cholangitis;
- cirrhosis of the liver;
- encephalopathy, incl. associated with liver failure (alcohol, etc.).
2. Intrahepatic cholestasis in pregnant women;
3. Symptoms of depression.
Contraindications
- Hypersensitivity to any of the components of the drug.
- Age up to 18 years.
The medicine should be used with caution when:
- Bipolar disorders (see section "Special instructions").
- Pregnancy (1st trimester).
- The period of breastfeeding (lactation).
Use during pregnancy and breastfeeding
The use of high doses of ademetionine in the third trimester of pregnancy did not cause any unwanted effects. The use of the drug Heptral in pregnant women in the first trimester and during breastfeeding possible only if the potential benefit to the mother exceeds possible risk for the fetus or child.
Side effects
Among the most common (common) adverse reactions are: nausea, abdominal pain and diarrhea. Below is a summary of information about adverse reactions, which were noted during the use of ademetionine both in tablets and in injection dosage form.
From the outside immune system: swelling of the larynx, allergic reactions.
From the skin: sweating, itching, rash, Quincke's edema, skin reactions.
Infections and infestations: urinary tract infections.
From the outside nervous system: dizziness, headache, paresthesia, anxiety, confusion, insomnia.
From the CCC side: 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, liver cirrhosis.
From the musculoskeletal system: arthralgia, muscle spasms.
Other: asthenia, chills, flu-like syndrome, malaise, peripheral edema, fever.
Instructions for use of Heptral
Use of tablets
Following the recommendations in the instructions for use, Heptral tablets should be taken orally between meals in the first half of the day, without chewing or crushing. The tablet is removed from the package immediately before use.
Daily dose - 2-4 tablets of 400 mg. The duration of treatment depends on the indications.
Ampoules of the drug
Heptral in ampoules is administered intravenously or intramuscularly. Intravenous injections perform very slowly.
The solution is prepared immediately before the injection, using a specially supplied solvent to dilute the lyophilized mass.
After the injection, the remaining medicine must be disposed of.
The injection form of Heptral is incompatible with preparations containing calcium ions and alkaline solutions.
The daily dose of the drug for VHD is 1-2 ampoules (400-800 mg of ademetionine per day). Treatment lasts for 2 weeks.
For depression, the drug is used in a similar dosage. Injections should be given within 15-20 days.
If maintenance treatment is necessary, the patient is transferred to the tablet form of ademetionine. Tablets are taken 2-4 pcs./day. for 2-4 weeks.
Overdose
There were no cases of overdose.
Interaction
No known drug interactions were observed.
There are reports of serotonin intoxication in a patient taking Clomipramine and Ademethionine.
Because such an interaction is considered potential, ademetionine preparations should be administered with great caution with tricyclic antidepressants, SSRIs, and tryptophan-containing herbs.
special instructions
Given the tonic effect of the drug, it is not recommended to take it before bed. When prescribing Heptral to patients with liver cirrhosis due to hyperazotemia, systematic monitoring of residual nitrogen is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.
There are also reports of sudden appearance or increased anxiety in patients taking ademetionine. In most cases, discontinuation of therapy is not required; in a few cases, anxiety resolved after dose reduction or drug discontinuation.
Since vitamin B12 and folic acid deficiency may reduce ademetionine levels in patients at risk (with anemia, liver disease, pregnancy or the possibility of vitamin deficiency due to other diseases or diet, such as vegetarians), vitamin levels should be monitored. If deficiency is detected, simultaneous administration of ademetionine with vitamin B12 and folic acid. Ademetionine influences the result of immunological analysis of homocysteine, which may cause false high level homocysteine in plasma. For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine homocysteine levels.
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 patients are sure that the therapy does not affect the ability to engage in these types of activities.
Heptral's analogs
Structural analogue: Heptor.
Drugs with a similar mechanism of action:
- Glutamic acid.
- Histidine.
- Carnitene.
- Carnitine.
- Elkar.
- Epilapton.
Terms of sale
The drug is available in pharmacies with a prescription.
Heptral is a hepatoprotective drug with antidepressant activity.
Release form and composition
Dosage forms of Heptral are tablets for oral administration and lyophilisate, from which a solution is prepared for intramuscular and intravenous administration.
Composition of tablets:
- 400 mg ademetionine ion (as ademetionine 1,4-butane disulfonate);
- Excipients: sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose;
- Shell composition: polysorbate 80, macrogol 6000, copolymer of methacrylic acid and ethyl acrylate (1:1 ratio), simethicone (30% emulsion), talc, sodium hydroxide, water.
Tablets are sold in packs of 10. in blisters packed in cardboard boxes.
1 bottle of Heptral solution contains 400 mg of ademetionine ion (in the form of ademetionine 1,4-butane disulfonate).
Composition of the included solvent: injection water, sodium hydroxide and L-lysine.
Indications for use
In accordance with the instructions for Heptral, the drug is intended for the treatment of intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in diseases such as:
- Chronic hepatitis;
- Fatty liver degeneration;
- Chronic acalculous cholecystitis;
- Cirrhosis of the liver;
- Cholangitis;
- Encephalopathy (including alcoholic), including those caused by liver failure;
- Toxic liver damage of various etiologies, including viral, toxic, alcoholic and medicinal (caused by taking antibiotics, antituberculosis, antiviral or antitumor drugs, tricyclic antidepressants, oral contraceptives).
In addition, indications for the use of Heptral are:
- Intrahepatic cholestasis of pregnancy;
- Depressive syndromes, incl. secondary.
Contraindications
According to the instructions for Heptral, the use of the drug is contraindicated:
- Under the age of 18 years (since experience in using the drug in pediatrics is limited);
- In case of hypersensitivity to components;
- In the presence of genetic disorders that affect the methionine cycle and/or cause homocystinuria and/or hyperhomocysteinemia (this could be, for example, a disorder of vitamin B12 metabolism or cystathionine beta synthase deficiency).
The drug is prescribed, but treatment is carried out under special medical supervision:
- At bipolar disorders;
- During breastfeeding;
- In the first trimester of pregnancy;
- To old people;
- In case of renal failure.
Particular caution should be observed if it is necessary to use Heptral simultaneously with tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), as well as medicines, which contain tryptophan.
Directions for use and dosage
Heptral solution prepared from lyophilisate (the powder is mixed with the solvent supplied in the box immediately before administration) is intended for intramuscular or very slow intravenous administration. Lyophilisate can only be used if it is white or white with a yellowish tint. If the shade is different (which may occur as a result of exposure to heat or a minor crack in the bottle), the product should not be used.
For intrahepatic cholestasis, the drug is prescribed at a dose of 400-800 mg (1-2 bottles) for 14 days.
For depression, Heptral is administered in a dosage of 400-800 mg. The course of treatment is from 15 to 20 days.
If maintenance therapy is necessary, the patient is transferred to oral administration of the drug.
Heptral tablets, according to the instructions, should be taken between meals in the first half of the day. They should be removed from the blister immediately before use. If their color differs from the original color (from white to white with a yellowish tint), which may occur as a result of leaking aluminum foil, such tablets should not be taken.
The recommended starting dose is 10-25 mg per kilogram of patient weight per day. In the future, depending on the clinical effect and tolerability of the drug, the daily dosage may be adjusted.
At depressive states and intrahepatic cholestasis, as a rule, 800-1600 mg per day is prescribed.
The duration of treatment in each case is determined individually.
Side effects
The most common side effects of Heptral are abdominal pain, nausea and diarrhea.
In some cases, the use of the drug may be accompanied by:
- Allergic reactions;
- Edema of the larynx;
- Reactions at the injection site (very rarely with skin necrosis);
- Quincke's edema, increased sweating, skin reactions;
- Urinary tract infections;
- Headache, anxiety, dizziness, paresthesia, insomnia, confusion;
- Phlebitis of superficial veins, hot flashes, cardiovascular disorders;
- Bloating, dry mouth, flatulence, esophagitis, vomiting, gastrointestinal bleeding, digestive disorders, hepatic colic, cirrhosis of the liver;
- Arthralgia, muscle spasms;
- General malaise, chills, asthenia, flu-like syndrome, fever, peripheral edema.
special instructions
The lyophilisate must not be mixed with alkaline solutions or solutions containing calcium ions. Rating: 4.8 - 24 votes
Heptral instructions for use of the drug
Tradename: Heptral ®
International generic 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 color;
- Prepared drug solution — clear solution Colorless to yellow with no 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 fast phase distribution in tissues and clearance with a half-life of about 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), indolamines (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
Instructions for use:
Heptral is a medicine intended to cleanse and restore the liver; has antidepressant activity.
pharmachologic effect
Heptral has choleretic (increases the amount of bile acids in bile), cholekinetic (promotes the release of bile into the intestines), regenerative, detoxifying (removes toxins from the body), antifibrinolytic (reduces the ability of the blood to spontaneously dissolve blood clots), antioxidant, antidepressant and neuroprotective (eliminates disorders in nerve cells) properties.
The active component of Heptral is ademetionine, which is a substance that is necessary for almost all tissues.
The use of Heptral allows not only to compensate for the deficiency of ademetionine, but also to stimulate its production in the liver, spinal cord, brain, and other organs.
Ademetionine plays important role in the metabolic processes of the body, participates in such important biochemical reactions as transmethylation, transsulfation, transamination, increases protective functions liver cells.
The use of Heptral allows you to normalize the production of bile acids, their entry into the biliary tract, and also improve motility digestive tract by eliminating stagnation of bile in liver cells. Hepatoprotective (cleansing and restoration of the liver) and choleretic effects of Heptral are observed for another 3 months after completion of the drug.
The level of ademetionine decreases with age, and the concentration of this substance is lower than normal in people with depressive syndrome. The use of Heptral allows you to increase the content of ademetionine in the body, in particular in brain tissue, which helps stabilize the transmission of nerve impulses and prolong the functioning of nerve cells.
Clinical studies and reviews of Heptral confirm the antidepressant effect of the drug, which develops quite quickly, and reaches maximum effectiveness on the 5-7th day of use of the drug.
Indications for use of Heptral
The instructions recommend prescribing and using Heptral for:
- intrahepatic cholestasis (reduction or cessation of bile secretion);
- chronic acalculous cholecystitis (acute inflammation of the gallbladder);
- cholangitis ( infectious inflammation bile ducts);
- toxic liver lesions of various etiologies;
- fatty liver;
- liver cirrhosis;
- chronic hepatitis;
- encephalopathy (non-inflammatory diseases of the brain);
- depression;
- withdrawal syndrome, including alcoholic.
Instructions for use and dosage
Heptral, the use of which is possible only as prescribed by a doctor, is available in the form of tablets and solution for injection.
Heptral tablets are enteric-coated and are intended for oral use; they should be swallowed whole, without chewing, with water (in a small amount). Recommended single dose, corresponding to 1 tablet of Hepral, should be taken 3-4 times a day. The duration of treatment is usually 3-4 weeks. It is advisable to take Heptral tablets between meals in the first half of the day.
Heptral lyophilisate in ampoules comes with L-lysine solvent. The drug is prescribed intravenously or intramuscularly in daily dose, equal to 400-800 mg. Intensive therapy Heptral in ampoules is carried out in the first 2-3 weeks of treatment, maintenance - for the next 2-4 weeks (800-1600 mg/day).
Side effects
Usually Heptral, reviews confirm, is well tolerated.
Only in rare cases, reactions in the form of heartburn, dyspepsia (painful and difficult digestion), gastralgia (stomach cramps), changes in sleep rhythm, itching and skin rashes are possible.
Contraindications to the use of Heptral
According to the instructions, Heptral is not prescribed to persons with hypersensitivity To active substances the drug, pregnant women (I and II trimesters), lactating women, children and adolescents under 18 years of age.
Additional Information
The shelf life of this medicine is 3 years.
The drug Heptral, produced by the Italian branch of the American chemical and pharmaceutical corporation Abbott, belongs to the group of hepatoprotectors and is used mainly for certain liver pathologies. Why "mainly"? The fact is that active substance heptral - ademetionine - also has antidepressant activity, therefore, the number of indications for prescribing this drug also includes depressive disorders. But still, the main therapeutic “path” of heptral is to protect the liver. And for this, the drug is provided with everything necessary, such as: choleretic, cholekinetic, regenerating, detoxifying, antifibrosing, antioxidant and neuroprotective properties. Ademetionine is a natural substance synthesized in the liver. It is widely represented in all biological environments body (its highest content is observed in the liver and brain) and is involved in many metabolic processes, including the three most important: transmethylation, transsulfuration and aminopropylation. In transmethylation (remethylation) reactions, ademetionine “donates” its methyl group for the synthesis of membrane phospholipids, neurotransmitters, proteins, hormones, etc. In transsulfation reactions, it is a substrate for the formation of glutathione, cysteine, taurine, and acetylation coenzyme. Heptral, in turn, compensates for the lack of natural ademetionine and activates its reproduction in the body, increases the content of L-glutamine in the liver, cysteine and taurine in the blood plasma, and normalizes hepatic metabolism. The drug increases the production of bile in the liver: it normalizes the formation of endogenous phosphatidylcholine in liver cells, which increases the fluidity (motility) and polarization of cell membranes. This has a beneficial effect on the transport systems of bile acids associated with the membranes of liver cells and promotes the movement of the latter through the biliary system.
For this reason, Heptral is successfully used for intrahepatic bile stagnation. Ademetionine, along with ursodeoxycholic acid, is considered the most promising drug in terms of its impact on the key links in the pathogenesis of intrahepatic (intralobular and interlobular) cholestasis. Heptral has comprehensively proven its effectiveness in the treatment and prevention of hepatopathies associated with the use of hepatotoxic drugs. This has a special important in the treatment of cancer patients, when discontinuation of a hepatotoxic drug significantly reduces the effectiveness of chemotherapy and, as a result, worsens the prognosis of life. Prescribing Heptral to opioid drug addicts with hepatopathy leads to a reduction in withdrawal symptoms, improved liver function and normalization of microsomal oxidation processes. Another property of heptral that is unique to a hepatoprotector is its antidepressant properties. It begins to appear from the end of the first week of taking the drug, completely stabilizing within 2 weeks of pharmacotherapy. Heptral is effective for recurrent endogenous and neurotic depression resistant to amitriptyline.
Heptral is available in two dosage forms: tablets and lyophilisate for the preparation of a solution for intravenous and intramuscular administration. It is recommended to take the tablets in the first half of the day between meals. Important nuance: The tablets should be taken out of the package immediately before use. Packaging tightness - required condition to maintain the quality of the drug: if the color of the tablet is different from white (slight yellowness is allowed), it means that the seal has been broken and the drug can no longer be used for its intended purpose. Heptral solution for intravenous and intramuscular administration is prepared immediately before administration using the solvent included in the package. The remainder of the drug must be disposed of.
Pharmacology
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; 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 for cellular detoxification), acetylation coenzyme (included in biochemical reactions of the tricarboxylic acid cycle and replenishes the energy potential of the cell).
Increases the content of glutamine in the liver, cysteine and taurine in plasma; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in 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 system. Effective for intrahepatic (intralobular and interlobular) variants of cholestasis (impaired synthesis and flow of bile). Ademetionine 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 the hepatocyte. The process of sulfation of bile acids facilitates their elimination by the kidneys, facilitates their passage through the hepatocyte membrane and excretion with 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. 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.
Administration 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
Tablets coated film-coated, dissolving only in the intestine, due to this ademetionine is released in the duodenum.
Suction
The bioavailability of the drug when taken orally is 5%, increases when taken on an empty stomach. Cmax of ademetionine in plasma is dose-dependent and is 0.5-1 ml/l 3-5 hours after a single oral dose in doses of 400 to 1000 mg. Cmax of ademetionine in plasma decreases to baseline within 24 hours
Distribution
Binding to plasma proteins is insignificant, ≤ 5%. Penetrates through the BBB. There is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.
Metabolism
Biotransformed 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 reverse transformation to methionine by transfer of a methyl group from 5-methyltetrahydrofolate. Eventually, methionine can be converted to ademetionine, completing the cycle.
Removal
T 1/2 - 1.5 hours. Excreted by the kidneys. In studies in healthy volunteers, ingestion of labeled (methyl 14 C) S-adenosyl-L-methionine in urine showed 15.5 ± 1.5% radioactivity after 48 hours, and in feces - 23.5 ± 3.5% radioactivity after 72 hours. Thus, about 60% was deposited.
Release form
Tablets, enteric-coated, film-coated, white to white with a yellowish tint, oval, biconvex.
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.
Shell composition: copolymer of methacrylic acid and ethyl acrylate (1:1) - 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, water - Q.S.
10 pieces. - blisters (1) - cardboard packs.
10 pieces. - blisters (2) - cardboard packs.
Dosage
The drug is prescribed orally. The tablets should be swallowed whole, without chewing, preferably taken in the first half of the day between meals.
Heptral ® tablets should be removed from the blister immediately before oral administration. If the tablets have a color other than white to white with a yellowish tint (due to leakage of aluminum foil), the use of Heptral ® is not recommended.
Intrahepatic cholestasis
Depression
The dose ranges from 800 mg/day to 1600 mg/day.
The duration of therapy is determined by the doctor.
Elderly patients
Clinical experience with the use of the drug Heptral ® did not reveal any differences in its effectiveness in elderly patients and patients over young. However, given the high likelihood of existing liver, kidney or heart dysfunction, another 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 at the lower end of the dose range.
Patients with renal failure
Studies have not been conducted in patients with renal failure; therefore, caution is recommended when using the drug Heptral ® in such patients.
Patients with liver failure
Overdose
An overdose of Heptral ® is unlikely. In case of overdose, observation of the patient and symptomatic therapy are recommended.
Interaction
Famous drug interactions the drug Heptral ® with other drugs was not observed.
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.
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 with post-marketing use of ademetionine both in tablets and in injection dosage form.
From the immune system: hypersensitivity reactions, anaphylactoid or anaphylactic reactions(including hyperemia skin, shortness of breath, bronchospasm, back pain, discomfort in the area chest, decreased blood pressure, increased blood pressure, tachycardia, bradycardia).
From the outside respiratory system: swelling of the larynx.
From the skin: reactions at the injection site (very rarely with skin necrosis), Quincke's edema, increased sweating, skin reactions, allergic skin reactions (including rash, itchy skin, urticaria, erythema).
Infections and infestations: urinary tract infections.
From the nervous system: dizziness, headache, paresthesia, anxiety, confusion, insomnia.
From the outside of cardio-vascular system: "hot flashes", phlebitis of superficial veins, cardiovascular disorders.
From the outside 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.
Other: asthenia, chills, flu-like syndrome, malaise, peripheral edema, fever.
Indications
Intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
- fatty liver;
- chronic hepatitis;
- toxic liver damage of various etiologies, including alcohol, viruses, drugs (antibiotics, antitumor, antituberculosis and antiviral 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, impaired metabolism of vitamin B 12);
- age up to 18 years (experience medical use limited in children);
- hypersensitivity to the components of the drug.
The drug should be prescribed with caution for bipolar disorders; in the first trimester of pregnancy and during breastfeeding (use is possible only if the potential benefit to the mother outweighs the possible risk to the fetus and child); simultaneously with selective serotonin reuptake inhibitors (SSRIs); tricyclic antidepressants (such as clomipramine); herbal preparations and preparations containing tryptophan; elderly patients with renal failure.
Features of application
Use during pregnancy and breastfeeding
The use of ademetionine in high doses 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.
Use for liver dysfunction
The pharmacokinetic parameters of ademetionine are similar in healthy volunteers and patients with chronic diseases liver.
Use for renal impairment
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.Use in children
The use of Heptral ® in children is contraindicated (efficacy and safety have not been established).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 due to 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.
Patients with depression have increased risk 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 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 deficiency of cyanocobalamin and folic acid can reduce the content of ademetionine in patients at risk (with anemia, liver disease, pregnancy or the likelihood of vitamin deficiency due to other diseases or diet, for example, 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 one-day 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.
Impact on the ability to drive a car and operate machinery
Some patients may experience dizziness when 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 such activities.
