Heptrazan
Heptrazan: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Heptrasan
ATX code: A16AA02
Active ingredient: ademetionine (Ademetionine)
Manufacturer: National Medical Research Center of Cardiology of the Federal State Budgetary Institution of the Ministry of Health of the Russian Federation (Russia), ZiO-Zdorovie CJSC (Russia)
Description and photo update: 2019-11-07
Heptrazan is a hepatoprotective drug that has an antidepressant, antioxidant, hepatoprotective, detoxifying, neuroprotective effect.
Release form and composition
Dosage forms of Heptrazan:
- lyophilisate for preparing a solution for intravenous (i / v) and intramuscular (i / m) administration: freeze-dried mass from almost white to white; solvent - a colorless liquid, transparent or light yellow, after recovery, a clear solution is formed from colorless to yellowish ampoules without color with or without a break point), in a cardboard box 1 package or in a cardboard box 6 or 10 packages (for hospitals); 5 vials in blister packs and 5 ampoules with solvent in blister packs, in a cardboard box, 1 pack with bottles and ampoules,for hospitals - in a cardboard box of 6 or 10 packages with bottles and ampoules with a solvent];
- enteric tablets: film-coated white or almost white, oval, biconvex, core - from almost white to white (10 pcs. in blisters, in a cardboard box 1 or 2 packs; 20, 40 or 50 pcs. in polypropylene or polyethylene cans, in a cardboard box 1 can).
Each pack also contains instructions for the use of Heptrazan.
1 vial with lyophilizate contains the active ingredient - ademetionine 1,4-butanedisulfonate - in an amount of 760 mg, which is 400 mg in terms of ademetionine ion.
Solvent composition: L-lysine monohydrate, sodium hydroxide, water for injection.
1 tablet contains:
- active substance: ademetionine 1,4-butanedisulfonate - 760 mg, which corresponds to 400 mg of ademetionine ion;
- auxiliary components: microcrystalline cellulose, sodium carboxymethyl starch, colloidal silicon dioxide, magnesium stearate;
- composition of the film shell: copolymer of methacrylic acid and ethyl acrylate (1: 1), colloidal silicon dioxide, sodium lauryl sulfate, sodium bicarbonate, macrogol, simethicone emulsion 30%, talc.
Pharmacological properties
Pharmacodynamics
Heptrazan is a hepatoprotective drug with antidepressant activity, has a cholekinetic and choleretic effect. Its active substance - ademetionine - exhibits detoxifying, antioxidant, antifibrosing, regenerating and neuroprotective properties.
The use of Heptrazan helps to replenish the deficiency and stimulate the production of ademetionine in the body, primarily in the brain and liver. Ademetionine (a molecule of S-adenosyl-L-methionine) is a donor of the methyl group in the reactions of methylation of cell membrane phospholipids, proteins, hormones, neurotransmitters. Along with biological reactions of transmethylation, ademetionine, being a precursor of cysteine, taurine, glutathione, acetylation coenzyme, takes part in transsulfation reactions. Promotes an increase in the content of cysteine and taurine in plasma, glutamine - in the liver. Normalizes metabolic reactions in the liver, reducing serum methionine.
After decarboxylation, as a precursor of polyamines, it participates in the processes of aminopropylation of putrescine (stimulator of hepatocyte proliferation and cell regeneration), spermidine and spermine, which are part of the structure of ribosomes.
The choleretic effect of Heptrazan is a consequence of stimulating the synthesis of phosphatidylcholine in hepatocytes, which contributes to an increase in the mobility of hepatocytes and the polarization of their membranes. The function of the transport systems of bile acids improves, which facilitates the passage of bile acids into the bile excretory system. Effective for intralobular disorders of the synthesis and flow of bile. Potentiates the detoxification of bile acids, increases the content of conjugated and sulfated bile acids in hepatocytes. Against the background of conjugation of ademetionine with taurine, the solubility of bile acids and their excretion from the hepatocyte increase. Sulfation of bile acids makes it possible for their elimination through the kidneys, facilitates overcoming the hepatocyte membrane and excretion in the bile. Along with the,sulfated bile acids protect the membrane of liver cells from the toxic effects of non-sulfated bile acids. In intrahepatic cholestasis, unsulfated bile acids are present in high concentrations in hepatocytes.
In patients with intrahepatic cholestasis syndrome in patients with liver cirrhosis or hepatitis, ademetionine helps to reduce the severity of itching and changes in biochemical parameters such as direct bilirubin level, alkaline phosphatase activity, aminotransferases.
The effectiveness in hepatopathies, which are caused by the intake of various hepatotoxic drugs, has been confirmed.
The hepatoprotective and choleretic effects of Heptrazan persist for three months after the termination of its use.
Pharmacokinetics
After parenteral administration of Heptrazan, the maximum plasma concentration (C max) is reached within 3/4 hours, the bioavailability is 96%.
After taking an enteric tablet, the release of ademetionine due to the film shell occurs in the duodenum. After single oral doses of 400 to 1000 mg C max ademetionine plasma achieved after 3-5 hours and 0.5-1 ml / l. Plasma concentration is dose dependent. Bioavailability - 5%, when taken on an empty stomach increases. Within 24 hours C max ademetionine plasma acquires the initial level.
Plasma protein binding is less than 5%.
It overcomes the blood-brain barrier, a significant increase in concentration is noted in the cerebrospinal fluid.
The drug is metabolized in the liver. The ademetionine cycle includes the following three stages: formation, consumption and re-formation of ademetionine. At the first stage, it is used by ademetionine-dependent methylases as a substrate for the synthesis of S-adenosyl homocysteine, which is then hydrolyzed to homocysteine and adenosine using S-adenosyl homocysteine hydralase. The reverse biotransformation of homocysteine to methionine occurs as a result of the transfer of a methyl group from 5-methyltetrahydrofolate. The cycle is completed by the conversion of methionine to ademetionine.
The half-life (T 1/2) is 1.5 hours. It is excreted through the kidneys.
In chronic liver diseases, the pharmacokinetic parameters of Heptrazan are not violated.
Indications for use
The use of Heptrazan is indicated for cirrhotic and pre-cirrhotic conditions for the treatment of intrahepatic cholestasis, observed in diseases such as:
- chronic hepatitis;
- fatty degeneration of the liver;
- cirrhosis of the liver;
- toxic liver damage of various etiologies, including alcoholic, viral, drug (while taking antiviral, antineoplastic and / or anti-tuberculosis drugs, tricyclic antidepressants, antibiotics, oral contraceptives);
- cholangitis;
- encephalopathy, including those associated with liver failure (including alcoholic);
- chronic acalculous cholecystitis.
In addition, Heptrazan is prescribed for the symptomatic treatment of depression and for intrahepatic cholestasis in pregnant women.
Contraindications
Absolute:
- bipolar disorder;
- the presence of genetic abnormalities that affect the methionine cycle, causing homocystinuria and / or hyperhomocysteinemia (including impaired cyanocobalamin metabolism, cystathionine beta synthase deficiency);
- age up to 18 years;
- hypersensitivity to drug components.
With caution, Heptrazan should be prescribed for renal failure, concomitant use of selective serotonin reuptake inhibitors, tricyclic antidepressants (including clomipramine), herbal preparations or drugs containing tryptophan in old age.
The use of Heptrazan in the I-II trimesters of pregnancy and lactation is allowed only in exceptional cases, when the potential benefit of therapy to the mother is higher than the possible risk to the fetus or child.
Heptrazan, instructions for use: method and dosage
Lyophilisate for preparing a solution for intravenous and intramuscular administration
The ready-made lyophilisate solution is intended for intramuscular and intravenous administration.
Dissolution of the lyophilisate should be carried out immediately before administration using a special solvent supplied in the kit. The rest of the drug must be disposed of.
Do not mix Heptrazan with calcium ions and alkaline solutions!
It is not recommended to use the drug if, upon visual inspection of the contents of the vial, it is found that the color of the lyophilisate does not correspond to the one declared by the manufacturer in the instructions.
IV Heptrazan should be administered very slowly.
The dose of initial therapy is determined at the rate of 5–12 mg per 1 kg of the patient's body weight per day.
Recommended daily dosage:
- intrahepatic cholestasis: 400 to 800 mg (1-2 bottles) per day. Duration of treatment is 14 days;
- depression: 400 to 800 mg daily for 15–20 days.
If necessary, it is recommended to continue taking Heptrazan tablets in a dose of 2–4 pieces as maintenance therapy. a day for 14-28 days.
In elderly patients, the use of a lyophilisate solution should be started with the minimum recommended dose of 5 mg / kg.
Enteric tablets
Heptrazan tablets are taken orally, swallowing whole (without violating the integrity of the film shell), taking them out of the blister before taking them directly, preferably during the break between meals in the morning.
If the color of the tablet differs from that described in the instructions (from white to white with a yellow tinge), it cannot be taken.
The dose of initial therapy is determined at the rate of 10-25 mg per 1 kg of the patient's body weight per day.
For intrahepatic cholestasis and depression, the recommended daily dose is 800 to 1600 mg. The doctor prescribes the duration of the course of treatment individually.
In elderly patients, Heptrazan should be started with a daily dose of 10 mg / kg. It is necessary to take into account the high probability of the presence of concomitant pathologies in this category of patients, including age-related disorders of the kidney, liver or heart function, as well as simultaneous therapy with other drugs.
Side effects
Adverse events of Heptrazan (classified as follows: very often - ≥ 1/10, often - ≥ 1/100 and <1/10, infrequently - ≥ 1/1000 and <1/100, rarely - ≥ 1/10 000 and <1 / 1000, very rarely - <1/10 000, including isolated cases):
- from the gastrointestinal tract: often - dry mouth, abdominal pain, nausea, diarrhea; infrequently - vomiting, dyspepsia, gastrointestinal upset, flatulence, gastrointestinal pain and / or bleeding; rarely - esophagitis, bloating;
- from the nervous system: often - headache; infrequently - paresthesia, dizziness;
- from the immune system: infrequently - hypersensitivity reactions, shortness of breath, flushing of the skin, bronchospasm and other symptoms of anaphylactic or anaphylactoid reactions, including back pain, chest discomfort, arterial hypotension, arterial hypertension, changes in heart rate (tachycardia, bradycardia);
- from the respiratory system, chest and mediastinal organs: infrequently - laryngeal edema;
- from the side of the vessels: infrequently - arterial hypotension, hot flashes, phlebitis;
- from the musculoskeletal system: infrequently - muscle spasms, arthralgia;
- from the skin and subcutaneous tissues: often - itchy skin; infrequently - allergic reactions (including itching, rash, erythema, urticaria), angioneurotic edema, increased sweating;
- mental disorders: often - insomnia, anxiety; infrequently - confusion, agitation;
- infectious and parasitic pathologies: infrequently - urinary tract infections;
- general disorders and disorders at the injection site: infrequently - fever, chills, asthenia, reactions at the injection site, edema, skin necrosis at the injection site; rarely - malaise.
Overdose
Symptoms of an overdose of Heptrazan have not been established.
Treatment: careful monitoring of the patient's condition, if necessary, the appointment of symptomatic therapy.
special instructions
It is not recommended to take Heptrazan before bedtime.
Taking the drug for cirrhosis of the liver against the background of hyperazotemia should be accompanied by regular monitoring of the nitrogen content in the patient's blood, with prolonged therapy - by monitoring the level of creatinine and urea in the blood serum.
Treatment with ademetionine increases the risk of suicide and other serious adverse events in patients with depression, therefore, such patients should be under medical supervision to assess symptoms and treat depression.
When a feeling of anxiety appears or grows, the patient should inform the doctor, usually lowering the dose of ademetionine allows you to stop the undesirable phenomenon, otherwise Heptrazan should be canceled.
Deficiency of cyanocobalamin and folic acid in the blood plasma contributes to a decrease in the content of ademetionine during pregnancy, in patients with anemia, impaired liver function and other diseases, or on a diet (for example, vegetarians). It is necessary to control the level of vitamins, in case of its insufficiency, take measures to restore it.
It should be borne in mind that an immunological test can give a false indicator of the level of homocysteine in the blood, therefore, during the period of using Heptrazan, it is recommended to use other methods of analysis to determine the level of homocysteine.
Influence on the ability to drive vehicles and complex mechanisms
During the period of treatment with Heptrazan, patients are advised to be especially careful when performing potentially hazardous activities that require a high speed of psychomotor reactions and increased attention. It is possible to drive vehicles and mechanisms provided that the drug does not cause dizziness and other side effects in the patient.
Application during pregnancy and lactation
The use of Heptrazan in the I-II trimesters of the gestation period and during breastfeeding is possible only in cases where the potential benefit of therapy to the mother is higher than the possible risk to the fetus or child.
Pediatric use
The efficacy and safety of using ademetionine for the treatment of children and adolescents has not been established, therefore, the appointment of Heptrazan is contraindicated in patients under 18 years of age.
With impaired renal function
Patients with renal insufficiency should take Heptrazan with caution.
For violations of liver function
No dose adjustment is required for chronic liver disease.
Use in the elderly
It is recommended to prescribe Heptrazan with caution to elderly patients.
When selecting a dose, one should take into account the high probability of the patient having concomitant pathologies, as well as the need for regular use of other drugs. Therefore, the initial dose of Heptrazan should not exceed the lower limit of the dose range: when taken in the form of enteric tablets, the daily dose is 10 mg / kg, when using a lyophilisate solution, the minimum recommended dose is 5 mg / kg.
Drug interactions
There is a risk of a clinically significant interaction with the simultaneous use of ademetionine with selective serotonin reuptake inhibitors, clomipramine and similar tricyclic antidepressants, phytopreparations, drugs containing tryptophan.
Analogs
Analogues of Heptrazan are: Ademetionine, Ademetionine-Vial, Heparetta, Heptor, Heptral, Samelix, etc.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Heptrazan
There are currently no reviews of Heptrazan in social networks.
Price for Heptrazan in pharmacies
The price for Heptrazan for a package containing 20 tablets can be from 880 rubles, 5 vials of lyophilisate (complete with 5 ampoules of solvent) - from 1122 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
