Heptral for the treatment of the liver. Heptral for intravenous drip Heptral for intravenous administration instructions for use
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Heptral- hepatoprotector, has antidepressant activity. It has choleretic and cholekinetic effects. It has detoxifying, regenerating, antioxidant, anti-fibrosing and neuroprotective properties.
Replenishes the deficiency of ademetionine (the active substance 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 the methylation reactions of cell membrane phospholipids, proteins, hormones, neurotransmitters; transsulfation - a precursor of cysteine, taurine, glutathione (provides the redox mechanism of cellular detoxification), acetylation coenzyme. Increases the content of glutamine in the liver, cysteine \u200b\u200band taurine in plasma; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation processes as a precursor of polyamines - putrescine (a stimulator of cell regeneration and hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure.
It has a choleretic effect due to an increase in the mobility and polarization of hepatocyte membranes, due to the stimulation of the synthesis of phosphatidylcholine in them. This improves the function of the bile acid transport systems associated with the hepatocyte membranes and facilitates the passage of bile acids into the biliary system. Effective for intralobular cholestasis (violation of the 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 excretion from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates the passage through the hepatocyte membrane and excretion with bile. In addition, sulfated bile acids protect the liver cell membranes from the toxic effects of unsulfated bile acids (present in high concentrations in hepatocytes in intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of itching and changes in biochemical parameters, incl. direct bilirubin level, alkaline phosphatase activity, aminotransferases.
The choleretic and hepatoprotective effect lasts up to 3 months after stopping treatment.
It has been shown to be effective in hepatopathies caused by hepatotoxic drugs.
Prescribing the drug to patients with opioid addiction accompanied by liver damage leads to a regression of the clinical manifestations of abstinence, an improvement in the functional state of the liver and microsomal oxidation processes.
Antidepressant activity manifests itself gradually, starting at the end of the first week of treatment, and stabilizes within 2 weeks of treatment. The drug is effective in 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 intestine, thanks to which ademetionine is released in the duodenum. Serum protein binding 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. It is excreted by the kidneys.
Indications
- chronic acalculous cholecystitis;
- cholangitis;
- intrahepatic cholestasis;
- toxic liver damage of various etiologies (including alcoholic, viral, medicinal / antibiotics, antineoplastic agents, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives /);
- fatty degeneration of the liver;
- chronic hepatitis;
- cirrhosis of the liver;
- encephalopathy, incl. associated with liver failure (including alcoholic);
- depression (including secondary);
- withdrawal syndrome (including alcoholic).
Release forms
Enteric-coated tablets 400 mg.
Lyophilisate for the preparation of a solution for intravenous and intramuscular administration (injections in ampoules for injection).
Instructions for use and dosage
Tablets
The drug is administered orally in a daily dose of 800-1600 mg. The duration of maintenance therapy can be on average 2-4 weeks.
The tablets should be swallowed whole, without chewing, preferably taken in the morning, between meals.
Ampoules
Applied intravenously or intramuscularly.
The lyophilisate must be dissolved in a specially supplied solvent immediately before administration. The rest 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 different from almost white to white with a yellowish tinge (due to a crack in the bottle or exposure to heat), the Heptral preparation is not recommended.
When administered intravenously, the drug 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 the drug Heptral in the form of tablets 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 up to 18 years;
- hypersensitivity to drug components.
Application during pregnancy and lactation
Application in children
Contraindicated in children and adolescents under the age of 18.
special instructions
Considering the tonic effect of Geptral, it is not recommended to use it before bedtime.
When Heptral is prescribed to patients with cirrhosis of the liver against the background of 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 is different from the proper white, you must refrain from using it.
Drug interactions
No known drug interaction of the drug Heptral with other drugs was observed.
Analogs of the drug Heptral
Structural analogues for the active substance:
- S-adenosyl-L-methionine disulfate p-toluenesulfonate;
- S-Adenosylmethionine;
- Ademethionine 1,4-butanedisulfonate;
- Heptor;
- Heptor N.
In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and see the available analogues for the therapeutic effect.
Heptral is a hepatoprotective agent with antidepressant activity.
The main active ingredient is ademetionine, which has regenerating, detoxifying, anti-fibrosing, antioxidant and neuroprotective properties. The drug compensates for the deficiency of ademetionine (the active substance Heptral) and stimulates its production in the body, primarily in the liver and brain.
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Clinical and pharmacological group
Hepatoprotector, has antidepressant activity.
Terms of dispensing from pharmacies
Dispensed by prescription.
Prices
How much does Geptral cost? The average price in pharmacies is at the level of 1,700 - 1,900 rubles.
Release form and composition
Dosage forms of Heptral are tablets for oral administration and a lyophilisate, from which a solution is prepared for intramuscular and intravenous administration.
Composition of tablets:
- 400 mg ademetionine ion (as ademetionine 1,4-butanedisulfonate);
- 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 (emulsion 30%), talc, sodium hydroxide, water.
Tablets are sold for 10 pcs. in blisters, packed in cardboard boxes.
- 1 bottle of Heptral solution contains 400 mg of ademetionine ion (in the form of ademetionine 1,4-butanedisulfonate).
The composition of the supplied solvent: injection water, sodium hydroxide and L-lysine.
Pharmacological effect
Heptral promotes antioxidant, antidepressant, neuroprotective, hepatoprotective, choleretic, detoxifying effects.
- When using the medication, the detoxification of bile acids is enhanced.
- The work of the transport systems of bile acids improves and the output of bile into the bile excretory system is normalized. The provision of choleretic and hepatoprotective action persists for 12 weeks after the termination of the use of the drug Heptral.
- Antidepressant activity manifests itself gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. Has the ability to interrupt relapses of depression.
- Effective in recurrent endogenous and neurotic depression resistant to amitriptyline.
- Prescription for osteoarthritis reduces the severity of pain, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.
- Long-term use of the drug increases plasma cysteine \u200b\u200band taurine, as well as glutamine in the liver. Methionine decreases, and metabolic processes in the liver are normalized, and the functioning of the organ normalizes.
The active component of the drug helps not only restore ademetionine, but also stimulate its production in the liver, brain and spinal cord, as well as in other organs.
Indications for use
What does it help from? The indications for the appointment of Heptral are:
- Cholangitis.
- chronic course.
- Expressed.
- Signs of severe depression.
- Chronic stoneless.
- Intrahepatic cholestasis in pregnant women (impaired synthesis and outflow of bile).
- Encephalopathy, including those caused by liver failure (including alcoholic).
- Intrahepatic cholestasis against the background of cirrhotic and pre-cirrhotic conditions (including fatty degeneration of the liver).
- Toxic liver damage of various origins, including viral, alcoholic, medicinal (oral contraceptives, tricyclic antidepressants, antibiotics, anti-tuberculosis, antineoplastic and antiviral drugs).
Contraindications
Despite the numerous positive qualities of this drug, there are a number of restrictions on its intake, which just act as contraindications. These include individual intolerance to one of the components of Heptral, due to the increased sensitivity of the body.
The drug is prescribed with caution to patients with bipolar disorders.
Application during pregnancy and lactation
The use is contraindicated in women in the I and II trimester of pregnancy.
The drug can be prescribed in the last trimester of pregnancy if the effectiveness of the drug for the mother is higher than the potential risk to the child. In many reviews about Heptral, it is recommended to stop breastfeeding while taking the drug.
Instructions for use
The instructions for use indicate that Heptral is available in the form of tablets and solution for injection.
- Heptral tablets enteric coated and intended for oral administration, they should be swallowed whole, without chewing, washed down with water (in a small amount). The recommended single dose, corresponding to 1 tablet of Heprala, should be taken 3-4 times a day. The duration of treatment is usually 3-4 weeks. It is advisable to take Geptral tablets between meals in the morning.
- Lyophilizate Heptral in ampoules attached solvent L-lysine. Intravenous drip or intramuscular injection, the drug is prescribed in a daily dose of 400-800 mg. Intensive therapy with Heptral in ampoules is carried out in the first 2-3 weeks of treatment, supporting therapy for the next 2-4 weeks (800-1600 mg / day).
Side effects
Most often, diarrhea, abdominal pain and nausea occurred during treatment with the drug. Sometimes the use of Heptral (i / v, i / m or in tablets) can cause:
- anxiety, insomnia, headache, confusion, paresthesia, dizziness;
- disturbances in the activity of blood vessels and heart, inflammation of the walls of superficial veins, hot flashes;
- digestive tract, liver cirrhosis;
- muscle spasm, joint pain;
- hypersensitivity reactions, laryngeal edema;
- skin manifestations of allergies, itching, rash, sweating, Quincke's edema;
- UTI (urinary tract infections);
- malaise, fever, flu-like syndrome, chills, asthenia, peripheral edema;
- dry mouth, bloating, esophagitis, abdominal pain, dyspepsia, diarrhea, flatulence, vomiting, hepatic colic, nausea, bleeding from different parts of the gastrointestinal tract, functional disorders.
Overdose
If the dose indicated by the doctor is exceeded or if the patient is used for a long time, an overdose may develop, which manifests itself in the form of an increase in the above-described side effects. There is no antidote to the drug. In case of an overdose with Heptral, the patient must be given to take enterosorbents and sent to a doctor.
special instructions
- Patients with depression need close supervision and constant psychiatric care during treatment with ademetionine in order to monitor the effectiveness of treatment.
- Deficiency of vitamin B12 and folic acid can lead to a decrease in ademetionine concentrations, therefore, their concomitant use in normal doses is recommended.
- When used in patients with cirrhosis of the liver against the background of hyperazotemia, systematic monitoring of the level of nitrogen in the blood is required. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.
- Use ademetionine with caution in patients with renal failure, with bipolar disorders, simultaneously with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine); herbal preparations and preparations containing tryptophan; in elderly patients.
When using ademetionine, dizziness is possible. Patients should not drive vehicles or work with other mechanisms until the symptoms disappear completely, which may affect the reaction rate during these activities.
Drug interactions
There is a report on the development of serotonin syndrome in a patient who used ademetionine and clomipramine.
Ademetionine should be used with caution in conjunction with selective serotonin reuptake inhibitors, tricyclic antidepressants, drugs and herbal remedies containing tryptophan.
Hepatoprotector
Active substance
Release form, composition and packaging
Lyophilisate for preparation of solution for intravenous and intramuscular administration from almost white to white with a yellowish tinge; solvent - a clear solution from colorless to light yellow; the reconstituted solution is a clear solution from colorless to yellow.
Solvent: L-lysine - 324.4 mg, sodium hydroxide - 11.5 mg, water d / i - up to 5 ml.
Vials of colorless glass type I (5) complete with solvent (amp. 5 ml 5 pcs.) - cardboard packs.
Vials of colorless glass type I (5) complete with solvent (amp. 5 ml 5 pcs.) - contoured plastic cell packs (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, anti-fibrosing and neuroprotective properties.
Replenishes the deficiency of S-adenosyl-L-methionine (ademetionine) and stimulates its production in the body, is contained in all environments of the body. The highest concentration of ademetionine was found in the liver and brain. Plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transsulfurization, transamination. In transmethylation reactions ademetionine gives up a methyl group for the synthesis of phospholipids of cell membranes, neurotransmitters, nucleic acids, proteins, hormones, etc. In the reactions of transsulfation, ademetionine is a precursor of cysteine, taurine, glutathione (providing the redox mechanism of cellular detoxification), coenzyme A (involved in the biochemical reactions of the tricarboxylic acid cycle and replenishes the energy potential of the cell).
Increases the content of glutamine in the liver, cysteine \u200b\u200band taurine; reduces the content of methionine in serum, normalizing metabolic reactions in the liver. After decarboxylation, it participates in aminopropylation processes 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.
It has a choleretic effect. Ademetionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases the fluidity and polarization of membranes. This improves the function of hepatocyte membrane-associated bile acid transport systems and facilitates the passage of bile acids into the bile ducts. Effective for intralobular cholestasis (violation of the synthesis and flow of bile). Ademetionine reduces the toxicity of bile acids in the hepatocyte, carrying out their conjugation and sulfation. Conjugation with increases the solubility of bile acids and their excretion from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates the passage through the hepatocyte membrane and excretion with bile. In addition, sulfated bile acids themselves additionally protect the membranes of liver cells from the toxic effect 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 itching and changes in biochemical parameters, incl. concentration of direct bilirubin, activity of alkaline phosphatase, aminotransferases, etc. The choleretic and hepatoprotective effect persists up to 3 months after stopping treatment.
It has been shown to be effective in hepatopathies caused by various hepatotoxic drugs.
Antidepressant activity manifests itself gradually, starting at the end of the first week of treatment, and stabilizes within 2 weeks of treatment.
Pharmacokinetics
Suction
Bioavailability for parenteral administration is 96%, plasma concentration reaches maximum values \u200b\u200bafter 45 minutes.
Distribution
The connection with blood plasma proteins is insignificant, is ≤ 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. At the first stage of this cycle, ademetionine-dependent methylases use ademetionine as a substrate for the production of S-adenosyl homocysteine, which is then hydrolyzed to homocysteine \u200b\u200band adenosine by S-adenosyl homocysteine \u200b\u200bhydralase. Homocysteine, in turn, undergoes reverse transformation to by methyl group transfer from 5-methyltetrahydrofolate. Eventually, methionine can be converted to ademetionine, completing the cycle.
Withdrawal
The half-life (T 1/2) is 1.5 hours. It is excreted by the kidneys.
Indications
- intrahepatic cholestasis in pre-cirrhotic and cirrhotic conditions, which can be observed in the following diseases:
Fatty degeneration of the liver;
Chronic hepatitis;
Toxic liver damage of various etiologies, including alcoholic, viral, medicinal (antibiotics, antitumor, anti-tuberculosis and 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 (deficiency of cystathionine beta-synthase, metabolic disorder);
- bipolar disorder;
- age up to 18 years (experience of medical use in children is limited);
- hypersensitivity to any component of the drug.
Carefully
Pregnancy (I trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child).
Concomitant use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), as well as herbal preparations and preparations containing tryptophan (see section "Drug Interactions").
Elderly age.
Renal failure
Dosage
Apply i / v and i / m.
Before use, the lyophilisate for intramuscular and intravenous administration should be dissolved using the supplied solvent. The rest of the drug must be disposed of. The corresponding dose of the drug for intravenous administration should be further 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 different from almost white to white with a yellowish tinge (due to a crack in the bottle or exposure to heat), the drug is not recommended to be used.
Depression
The drug is administered at a dose of 400 mg / day to 800 mg / day (1-2 bottles / day) for 15-20 days.
Intrahepatic cholestasis
The drug is administered at a dose of 400 mg / day to 800 mg / day (1-2 bottles / day) for 2 weeks.
If necessary, maintenance therapy is recommended to continue taking the drug Heptral in the form of tablets at a dose of 800-1600 mg / day for 2-4 weeks.
Therapy with Heptral can be started with intravenous or intramuscular injection, followed by the use of Heptral in the form of tablets or immediately with the use of the drug in the form of tablets.
Elderly patients
Clinical experience with the use of the drug Heptral did not reveal any differences in its effectiveness in elderly patients and younger patients. However, given the high likelihood of existing liver, kidney or cardiac dysfunction, other concomitant pathology or simultaneous therapy with other drugs, the dose of Heptral for elderly patients should be selected with caution, starting with the lower limit of the dose range.
Renal failure
There are limited clinical data on the use of the drug Heptral in patients with renal insufficiency, in this regard, it is recommended to be careful when using the drug Heptral in this group of patients.
Liver failure
Pharmacokinetic parameters of ademetionine are similar in healthy volunteers and in patients with chronic liver disease.
Children
The use of the drug Heptral in children is contraindicated (efficacy and safety have not been established).
Side effects
Among the most common adverse reactions identified in clinical trials involving more than 2,100 patients were headache, nausea and diarrhea. Below are data on adverse reactions observed in clinical trials (n \u003d 2115) and with 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 | Unwanted effects |
| From the immune system | |
| Infrequently | Hypersensitivity reactions Anaphylactoid or anaphylactic reactions (including skin hyperemia, shortness of breath, bronchospasm, back pain, chest discomfort, changes in blood pressure (arterial hypotension, arterial hypertension) or pulse rate (tachycardia, bradycardia)) * |
| Mental disorders | |
| Often | Anxiety Insomnia |
| Infrequently | Agitation Confusion of consciousness |
| From the nervous system | |
| Often | Headache |
| Infrequently | Dizziness Paresthesia Dysgeusia * |
| From the side of the vessels | |
| Infrequently | "Tides" Arterial hypotension Phlebitis |
| From the respiratory system, chest and mediastinal organs | |
| Infrequently | Laryngeal edema * |
| From the digestive tract | |
| Often | Abdominal pain Diarrhea Nausea |
| Infrequently | Dry mouth Dyspepsia Flatulence Gastrointestinal pain Gastrointestinal bleeding Gastrointestinal Disorders Vomiting |
| Seldom | Bloating Esophagitis |
| From the skin and subcutaneous tissues | |
| Often | Itchy skin |
| Infrequently | Increased sweating Angioedema * Skin and allergic reactions (including rash, pruritus, urticaria, erythema) * |
| From the musculoskeletal system and connective tissue | |
| Infrequently | Arthralgia Muscle spasms |
| General disorders and disorders at the injection site | |
| Infrequently | Asthenia Edema Fever Chills* Injection site reactions * Skin necrosis at the injection site * |
| Seldom | Malaise |
* Adverse events identified with post-marketing use of ademetionine ("spontaneous" messages) that were not observed in clinical trials were classified as adverse effects with a frequency of occurrence of "infrequent" on the basis that the upper limit of the 95% confidence interval for the assessment of occurrence did not exceed 3 / X, where X \u003d 2115 (total number of subjects observed in clinical trials).
Overdose
An overdose of the drug Heptral is unlikely. In case of overdose, it is recommended to monitor the patient and conduct symptomatic therapy.
Drug interactions
No known drug interaction of the drug Heptral with other drugs was observed.
There is a report of the serotonin excess syndrome in a patient taking ademetionine and clomipramine. It is believed that such an interaction is possible and should be used with caution in prescribing ademetionine together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbal medicines 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 cirrhosis of the liver against the background of hyperazotemia, systematic monitoring of the nitrogen content in the blood is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.
There are reports of the transition of depression to hypomania or mania in patients taking ademetionine.
Patients with depression have an increased risk of suicide and other serious adverse events, therefore, during treatment with ademetionine, such patients should be under constant medical supervision to assess and treat symptoms of depression. Patients should inform the doctor if their symptoms of depression do not decrease or worsen with ademetionine therapy.
There are also reports of a sudden onset or increase in anxiety in patients taking ademetionine. In most cases, withdrawal of therapy is not required, in several cases the state of anxiety disappeared after dose reduction or drug withdrawal.
Since the deficiency of cyanocobalamin and can reduce the content of ademetionine in patients at risk (with anemia, liver disease, during pregnancy or the likelihood of vitamin deficiency, due to other diseases or diet, for example, in vegetarians), the content of vitamins in the blood plasma should be monitored. If a deficiency is found, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademetionine or concurrently with ademetionine.
In an immunological analysis, the use of ademetionine can contribute to a false determination of an indicator of a high level of homocysteine \u200b\u200bin the blood. For patients taking ademetionine, it is recommended to use non-immunological assays to determine the level of homocysteine.
One vial of the drug 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 sodium chloride and is 0.3% of the recommended maximum daily intake of sodium for an adult.
Influence on the ability to drive and operate machinery
Some patients may experience dizziness while taking Geptral. It is not recommended to drive a car and work with mechanisms while taking the drug until the patient is sure that the therapy does not affect the ability to engage in this type of activity.
Pregnancy and lactation
In clinical studies, it was shown that the use of ademetionine in the third trimester of pregnancy did not cause any undesirable effects.
The use of the drug 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.
With impaired renal function
Shelf life 3 years. Do not use the drug after the expiration date.
One bottle contains
active substance - ademetionine 1,4-butanedisulfonate 760 mg (equivalent to 400 mg of ademetionine cation)
excipients:water for injection, nitrogen.
One ampoule of solvent contains
active substances: L-lysine 342.4 mg,
sodium hydroxide 11.5 mg,
excipients - water for injections.
Description
Lyophilized powder - lyophilized mass from white to slightly yellow, free from foreign particles.
Solvent - a clear liquid from colorless to slightly yellowish, free from foreign particles, with a characteristic amine odor.
Prepared drug solution - clear solution from light yellow to yellow.
Pharmacotherapeutic group
Other drugs for the treatment of gastrointestinal diseases and metabolic disorders. Amino acids and their derivatives. Ademetionine.
ATX code А16А А02
Pharmacological properties
Pharmacokinetics
Absorption
In humans, after intravenous administration, the pharmacokinetic profile of ademetionine is biexponential with a rapid phase of distribution in tissues and clearance with a half-life of about 1.5 hours. Absorption with intramuscular administration is 96%, maximum plasma concentrations are reached after 45 minutes. after application. After oral administration of enteric tablets of ademetionine (400-1000 mg), the maximum plasma concentrations achieved are dose-dependent and amount to 0.5-1 mg / l after 3 to 5 hours. Bioavailability after oral administration is increased if ademetionine is used between meals. Plasma concentrations decline to baseline values \u200b\u200bwithin 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. Serum protein binding is insignificant and is ≤ 5%.
Metabolism
The metabolic process of ademetionine is cyclic and is called the ademetionine cycle. At the first stage of this cycle, ademetionine-dependent methylase uses ademetionine as a substrate for the production of S-adenosyl-homocysteine, which is then hydrolyzed to homocysteine \u200b\u200band adenosine by S-adenosyl-homocysteine \u200b\u200bhydralase. 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.
Withdrawal
Approximately 60% of the total number of healthy volunteers who participated in studies on the ingestion of radioactive (methyl 14C) ademetionine, renal excretion was 15.5 ± 1.5% after 48 hours, excretion with feces - 23.5 ± 3.5% after 78 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 the brain tissue, due to the 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 essential for liver detoxification. Heptral increases glutathione levels in patients with liver damage, both alcoholic and non-alcoholic. Folic acid and vitamin B12 are essential co-nutrients in the metabolism and accumulation of Heptral (ademetionine).
Intrahepatic cholestasis
The drug is effective in the treatment of intrahepatic cholestasis in liver diseases, during pregnancy and other chronic hepatic diseases.
Intrahepatic cholestasis is a complication of chronic liver disease and causes damage to liver cells.
In chronic liver diseases, hepatocyte functions such as clearance and regulation of bile acid production are impaired, which leads to the development of intrahepatic cholestasis.
The use of ademetionine has been studied in patients with chronic liver diseases, often accompanied by intrahepatic cholestasis: primary biliary cirrhosis, primary sclerosing cholangitis, drug-induced liver damage, viral hepatitis; cholestasis induced by parenteral nutrition, liver damage of alcoholic and non-alcoholic genesis.
Depression
Heptral (ademetionine) has been used parenterally and orally to treat depression. The antidepressant effect appeared on the 5-7th day of treatment in the absence of side effects, including anticholinergic reactions.
Intrahepatic cholestasis of pregnancy
Treatment with ademetionine (i / v, i / m, orally in the form of tablets) is effective for intrahepatic cholestasis of pregnant women and is manifested in the form of a decrease in pruritus and an improvement in biochemical parameters.
Indications for use
Intrahepatic cholestasis in pre-cirrhotic conditions and liver cirrhosis
Intrahepatic cholestasis in pregnant women in the third trimester
Depressive syndrome
Method of administration and dosage
Treatment can be started with parenteral administration of the drug (intravenously slowly or intramuscularly) followed by the use of the drug in the form of tablets or immediately with the use of tablets.
The lyophilized powder is dissolved in a special solvent immediately before use. Discard any unused residue.
Heptral should not be mixed with alkaline solutions, or with solutions containing calcium ions. Do not use the powder if its color changes from the original from white to yellowish (due to damage to the bottle or heating). Intravenous administration is very slow
Adults
Initial therapy (parenteral administration):The recommended dose is 5-12 mg / kg / day intravenously or intramuscularly for the first 2 weeks. The usual starting dose is 400 mg per day. The daily dose should not exceed 800 mg. The duration of initial therapy is 15-20 days for the treatment of depressive syndrome, 14 days for the treatment of intrahepatic cholestasis in pre-cirrhotic conditions and liver cirrhosis, intrahepatic cholestasis in pregnant women in the third trimester.
When conducting initial therapy with Heptral in the form of tablets (oral administration): The recommended dose is 10-25 mg / kg / day. The usual starting dose is 400 mg 1–2 times a day. The daily dose should not exceed 1600 mg.
Supportive therapy: 2 - 3 tablets per day, by mouth (800 - 1600 mg / day).
The duration of therapy depends on the severity and course of the disease and is determined by the doctor individually.
Elderly patients.
It is recommended to start treatment with the lowest recommended dose, taking into account the decrease in hepatic, renal or cardiac function, the presence of concomitant pathological conditions and the use of other drugs.
Use in patients with renal impairment
Studies have not been conducted in patients with renal failure. Therefore, ademetionine in such patients is recommended to be used with caution.
Use in patients with hepatic impairment Pharmacokinetic parameters in healthy volunteers and patients with hepatic insufficiency are the same.
Side effects
Side effects from clinical studies
Often (≥1 / 100,<1/10)
Nausea, abdominal pain, diarrhea
Headache
Anxiety, insomnia
Itchy skin
Uncommon (≥ 1/1000,<1/100)
Dry mouth, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, gastrointestinal upset, vomiting
Asthenia, edema, fever, chills *, injection site reactions *, injection site necrosis *
Hypersensitivity, anaphylactoid reactions, or anaphylactic reactions (eg, flushing of the skin, shortness of breath, bronchospasm, back pain, chest discomfort, changes in blood pressure (hypotension, hypertension) or pulse rate (tachycardia, bradycardia)) *
Urinary tract infections
Arthralgia, muscle cramps
Dizziness, paresthesia
Agitation, confusion
Laryngeal edema *
Increased sweating, angioedema *, allergic skin reactions (eg, rash, pruritus, urticaria, erythema) *
- "hot flashes", hypotension, phlebitis
Rarely (≥ 1/10000,<1/1000)
Bloating, esophagitis
Malaise
* Adverse effects of post-marketing use ("spontaneous" messages) not observed in clinical trials were classified as infrequent effects, based on the fact that the upper limit of the 95% confidence interval for the assessment of occurrence does not exceed 3 / X, where X \u003d 2115 (total number of subjects observed in clinical trials).
Contraindications
Hypersensitivity to any component of the drug
Patients with a genetic defect affecting methionine metabolism and / or homocystinuria and / or hyperhomocysteinemia (eg, deficiency of the enzyme cystathione beta synthetase, defect in vitamin B12 metabolism)
Drug interactions
There was a report on the development of serotonin syndrome in a patient who used ademetionine and clomipramine. Heptral should be used with caution at the same time as selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), drugs and herbal remedies containing tryptophan.
special instructions
Intravenous administration is very slow.
Vitamin B12 and folic acid deficiencies can lead to decreased ademetionine concentrations, so patients at risk (anemia, liver failure, pregnancy, or the potential for vitamin deficiency due to other diseases or eating habits such as strict vegetarians) need to have daily blood tests. to check plasma levels. If a deficiency is found, treatment with vitamin B12 and folic acid is recommended simultaneously with the use of ademetionine.
Dizziness may occur in some patients during ademetionine therapy. You should not drive vehicles or work with other mechanisms until the symptoms disappear completely, which may affect the reaction rate during these activities.
Patients should be warned about the need to inform the doctor if, during therapy with Heptral, the symptoms of their disease (depression) persist or worsen. Patients with depression require close supervision and constant psychiatric care during treatment with ademetionine in order to monitor the effectiveness of treatment.
One literature report has been received on serotonin syndrome in a patient receiving ademetionine and clomipramine. Since the possibility of drug interactions is not ruled out, Heptral should be used with caution simultaneously with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), drugs and herbal remedies containing tryptophan.
There have been reports of transient or increasing anxiety in patients treated with Heptral (ademetionine). In most cases, no discontinuation of treatment was required. In some cases, the anxiety ceased after dose reduction or discontinuation of therapy.
(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 ademetionine in one bottle of lyophilisate - 400 mg. An ampoule with a solvent contains: L-lysine, Na hydroxide, water d / i.
Release form
- Tablets in a to / r shell; packing No. 10 and No. 20. Heptral tablets are oval, biconvex, white (yellowish tint is possible).
- Lyophilisate for preparation of solution for intramuscular and intravenous administration; 400 mg vial with solvent in ampoules 5 ml, packing No. 5. Lyophilized mass of white (yellowish-white) color, no foreign inclusions. Both the solvent and the reconstituted solution appear as a clear, colorless (slightly yellowish) liquid.
pharmachologic effect
Choleretic , detoxifying , hepato- and neuroprotective , cholekinetic , antioxidant , antidepressant .
Pharmacodynamics and pharmacokinetics
Pharmacodynamics
Substance ademetionine possesses hepatoprotective and antidepressant activity , as well as regenerating , detoxifying , neuroprotective , anti-fibrosing , antioxidant properties .
Hepatoprotective and choleretic effects after stopping treatment with Heptral, they persist up to three months.
Proven to be effective ademetionine at hepatopathies caused by the use of hepatotoxic drugs.
The appointment of Heptral to patients with opium addiction, which is accompanied by liver damage, improves liver function and monooxygenase oxidation processes, and also causes a regression of the clinical manifestations of drug withdrawal.
Antidepressant action develops gradually, from the end of the first week of the course of drug use. The effect stabilizes within 2 weeks of treatment.
The medicine is effective for recurrent depression (neurotic or endogenous) that are resistant to ... One of the properties of SAM is the ability to interrupt recurrent depression .
Contraindications
The use of ademetionine is contraindicated in genetic disorders that:
- affect the SAM cycle;
- cause hyperhomocysteinemia
- cause homocystinuria.
Other contraindications are children's age (Heptral is prescribed only to persons over 18 years of age) and intolerance to tablets / solution.
With caution, the drug should be used in patients with bipolar disorder (bipolar disorder), in the early stages (first 13 weeks) and during the period.
Side effects
Most often, during treatment with the drug, abdominal pain and nausea occurred.
Sometimes the use of Heptral (i / v, i / m or pills) can cause:
- hypersensitivity reactions, larynx;
- skin manifestations , itching, rash, ;
- IMP ( urinary tract infections );
- anxiety, confusion, paresthesias , ;
- disturbances in the activity of blood vessels and heart, inflammation of the walls of superficial veins, hot flashes;
- dry mouth, bloating, esophagitis , abdominal pain, dyspepsia, diarrhea, vomiting, hepatic colic , nausea, bleeding from different parts of the digestive tract, functional disorders of the digestive tract, ;
- muscle spasm, joint pain;
- malaise, flu-like syndrome, chills, asthenia, peripheral edema.
Instructions for the use of Heptral
How do I take the pills?
Following the recommendations in the instructions for use, Heptral tablets should be taken orally between meals in the morning, without chewing or crushing. The tablet is taken out of the package just before taking it.
The daily dose is 2-4 tablets of 400 mg. The duration of treatment depends on the indications.
Ampoules of Heptral: instructions for use
Heptral in ampoules is administered intravenously or intramuscularly. Intravenous injections are performed very slowly.
The solution is prepared just before the injection is made, using a solvent specially attached to it to dilute the lyophilized mass.
After the injection, the remaining medication should be discarded.
The injectable form of Heptral is incompatible with preparations containing calcium ions and alkaline solutions.
The daily dose of the drug for VPH is 1-2 ampoules (400-800 mg ademetionine per day). The treatment lasts for 2 weeks.
When depression the drug is used in a similar dosage. The injections should be given within 15-20 days.
If necessary, supportive treatment, the patient is transferred to a tablet form ademetioniina ... Tablets are taken 2-4 pcs / day. for 2-4 weeks.
Overdose
Overdose cases with the introduction of the drug intravenously, into the muscle and when taken orally were not observed.
Interaction
No known drug interactions have been observed.
There are reports of serotonin intoxication in a patient who took and Ademetionine .
Since this interaction is considered potentially possible, the drugs ademetionine should be administered with great care with tricyclic antidepressants , SSRIs and containing herbs.
Terms of sale
On prescription.
Storage conditions
Both the lyophilisate and the tablets must be stored at 15-25 ° C.
Shelf life
Three years.
special instructions
Ademetionine renders tonic effect , because of which the drug is not recommended to be taken in the afternoon and especially before bedtime.
If the medicine is used in patients with liver cirrhosis against the background of an increased content of nitrogen derivatives in the blood, it is necessary to systematically monitor the level of residual nitrogen.
Serum concentration monitoring is necessary during long-term treatment creatinine and urea .
Ademetionine should not be used to treat patients with bipolar disorder due to the possibility of transition depression in hypomania or mania .
Cases of sudden onset or escalation of anxiety are known to occur during therapy ademetionine ... As a rule, to normalize the patient's condition, it was enough to reduce the dose of the drug.
Level ademetionine may decrease with deficiency vitamins and , therefore, during the period of treatment, the level should be kept under control, especially in vegetarians, patients forced to adhere to a certain, and pregnant women, as well as with liver pathologies , anemia and some other conditions in which the risk of developing vitamin deficiency .
With confirmed vitamin deficiency it is recommended to supplement the treatment with a prescription folic acid and vitamin B12 .
Ademetionine alters immunoassay results in the blood, due to which the plasma concentration indicators homocysteine may be falsely elevated.
In this regard, for the host ademetionine patients should use non-immunological research methods to determine the concentration homocysteine .
Drivers and persons working with mechanisms should remember that during the period of treatment with Heptral, dizziness may occur. Engage in activities that require speed of reactions and attention only after the patient is firmly convinced that the treatment does not interfere with this.
Veterinary use
In veterinary medicine for treatment pre-cirrhotic conditions and cirrhosis , as a rule, the injectable form of the drug is used.
For cats, the dose, depending on the indication, varies from 0.7 to 2.5 ml of reconstituted solution. The dose for dogs is selected depending on the weight of the animal, while exceeding the dose does not pose a threat.
Analogs of Heptral
Matching ATX level 4 code:Drugs with a similar mechanism of action: Glutamic acid , , , Epilapton .
The price of analogs in tablets is from 645 rubles.
What's better - Heptral or Heptor?
Like Heptral, Heptor belongs to a group of drugs that increase resistance and activate the activity of liver cells.
The medicine is available in the form of tablets and a lyophilisate for the preparation of an injection solution, which include as an active substance ademetionine ... Moreover, both in tablets and in solution, the substance is contained in the same concentration as in Heptral.
Thus, the drugs are interchangeable. If the price plays a decisive role in choosing a medicine, a significant advantage of Heptor is a significantly lower cost in comparison with its analogue.
Geptral or Essentiale - which is better?
Essentiale - this is hepatoprotector based on soybean phospholipids. The drug promotes recovery hepatocytes and the normalization of well-being by eliminating symptoms such as decreased appetite, fatigue, heaviness in the right hypochondrium.
Essentiale prescribed for cirrhosis , hepatitis , steatohepatosis , , toxicosis of pregnant women , necrosis of hepatocytes , hepatic precoma / coma , before and after surgical interventions in the hepatobiliary zone, liver intoxication , radiation syndrome .
The difference between Geptral is that this drug can be used not only as a hepatoprotector, but also for treatment encephalopathy and depression .
Definitely say which is better - Heptral or / Essentiale N - for a specific patient, only a doctor who knows the features of the course of the disease can.
Phosphogliv or Heptral - which is better?
it hepatoprotector with antiviral activity ... The active components of the drug are glycyrrhizic acid (HA) and phospholipids.
Phosphatidylcholine contained in it is a component of the phospholipid layer of biological membranes, its action is aimed at restoring the structure and function of damaged membranes of liver cells, as well as the detoxification function of the liver, preventing the loss of active substances by cells (and others), normalizing fat, lipid and protein metabolism, suppressing proliferation of connective tissue in the liver, prevention of fibrosis and cirrhosis of the liver.
Under the influence of HA, the penetration of active particles of viruses into hepatocytes is blocked, and the ability of viruses to form new structural components is impaired.
The suppression of viral reproduction is carried out due to the stimulating effect of GA on IFN production, increased phagocytosis, increased activity of NK cells, etc. Due to its detergent action, HA promotes the emulsification of phosphatidylcholine in the intestine.
Phosphogliv is used to treat hepatosis , hepatitis , liver intoxication , cirrhosis , after cholecystectomy , as well as in the complex therapy of skin diseases ( eczema , neurodermatitis , psoriasis ).
For children
It is not used in pediatrics.
Heptral and alcohol: drug compatibility with alcohol
Alcohol is incompatible with Heptral.
One of the factors affecting the positive result of the treatment of liver pathologies is adherence to a strict diet, which implies a complete refusal to drink alcohol.
Application during pregnancy
During pregnancy and lactation, Heptral is used if the expected therapeutic effect outweighs the potential risks to the fetus / child.
It has been proven that the use of high doses ademetionine in the last months of pregnancy does not lead to the development of adverse reactions.