Ademetionine
Ademetionine: 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. Use in the elderly
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Ademetionine
ATX code: A16AA02
Active ingredient: ademetionine (Ademetionine)
Manufacturer: Biochemist, JSC (Russia)
Description and photo update: 2020-14-05
Ademetionine is a hepatoprotective drug with antidepressant activity.
Release form and composition
Dosage form - lyophilisate for the preparation of a solution for intravenous (i / v) and intramuscular (i / m) administration: almost white or white porous mass; complete with the drug there is a transparent colorless or yellowish solvent [in a cardboard box, instructions for use of Ademetionine, 5 vials of 400 mg of lyophilisate in each, equipped with 5 ampoules (5 ml) of solvent and a scarifier; for ampoules with a notch, dot or break ring, the scarifier is not included in the kit].
1 vial with lyophilisate contains an active substance - ademetionine, in an amount of 760 mg (corresponds to the content of ademetionine ion - 400 mg).
Composition of 1 ml of solvent: water for injection, 1 M sodium hydroxide solution, L-lysine monohydrate (in terms of L-lysine).
Pharmacological properties
Pharmacodynamics
Ademetionine is one of the hepatoprotective agents. It has a neuroprotective, antifibrosing, antioxidant, regenerating and detoxifying effect, has antidepressant activity, cholekinetic and choleretic properties.
The substance is present in all environments of the body, stimulates the production of ademetionine (S-adenosyl-L-methionine) and compensates for its deficiency. Its greatest content is found in the brain and liver.
Ademetionine plays a key role in the metabolic processes of the body, is involved in transamination, transsulfurization and transmethylation. In transmethylation reactions, it donates a methyl group, which leads to the synthesis of hormones, proteins, neurotransmitters of nucleic acids, phospholipids of cell membranes, etc. provides the redox mechanism of cellular detoxification), taurine and cysteine. It increases the concentration of taurine and cysteine in plasma, glutamine in the liver, lowers the content of methionine in the serum, thereby normalizing metabolic reactions in the liver.
Following decarboxylation, the drug participates in aminopropylation reactions as a precursor of putrescine (a polyamine that stimulates cell regeneration and hepatocyte proliferation), spermidine and spermine, which make up the ribosome structure. This reduces the likelihood of fibrosis.
Ademetionine has choleretic properties, helps to normalize the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases the polarization and fluidity of membranes. This, in turn, leads to an improvement in the function of the transport systems of bile acids associated with the membranes of hepatocytes, and facilitates the passage of bile acids into the biliary system. Shows efficiency in intrahepatic cholestasis, both intralobular and interlobular, reduces the toxicity of bile acids in the hepatocyte, carrying out their sulfation and conjugation. The combination with taurine increases the solubility of bile acids and their excretion from the hepatocyte. Sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates the passage through the hepatocyte membrane and excretion in the bile. At the same time, sulfated bile acids themselves are an additional protection of liver cell membranes from the toxic effects of non-sulfated bile acids, which are present in hepatocytes in increased concentrations with intrahepatic cholestasis.
In diffuse liver pathologies (hepatitis, cirrhosis) with intrahepatic cholestasis syndrome, the drug reduces the severity of pruritus and changes in biochemical parameters, including the activity of aminotransferases, alkaline phosphatase, direct bilirubin levels, etc. Within 3 months after discontinuation of therapy, hepatoprotective and choleretic effects. Ademetionine is indicated for the treatment of hepatopathies caused by various hepatotoxic agents.
Against the background of opioid addiction, accompanied by liver damage, ademetionine causes regression of clinical signs of withdrawal, improvement of the functional state of the liver and microsomal oxidation processes. Its antidepressant activity manifests itself gradually, starting from the end of the first week of therapy, and stabilizes over 14 days of use. Shows effectiveness in recurrent endogenous and neurotic depression resistant to amitriptyline.
Ademetionine may prevent relapse of depression. Application against the background of osteoarthritis promotes partial regeneration of cartilage tissue, an increase in the synthesis of proteoglycans, and a decrease in the severity of pain.
Pharmacokinetics
The biological availability of ademetionine for parenteral administration is 96%. The maximum concentration in blood plasma is reached 45 minutes after administration. It binds to blood plasma proteins to a small extent, at a level of less than 5%. Penetrates the blood-brain barrier. A significant increase in the content of the substance is noted in the cerebrospinal fluid. The metabolic process is carried out in the liver.
The period of formation, consumption and re-formation of the drug is called the ademetionine cycle. During the first stage of this cycle, ademetionine-dependent methylases use the substance as a substrate for the production of S-adenosyl homocysteine, which is then hydrolyzed to adenosine and homocysteine using S-adenosyl homocysteine hydralase. The latter, in turn, undergoes a reverse transformation to methionine by transfer of a methyl group from 5-methyl-tetrahydrofolate. As a result, methionine can be converted to ademetionine, completing the cycle.
The half-life of plasma is 1.5 hours. Excretion is mainly carried out by the kidneys.
Indications for use
Lyophilisate for the preparation of a solution for intravenous and intramuscular administration Ademetionine is prescribed for intrahepatic cholestasis and liver lesions of various origins:
- pre-cirrhotic and cirrhotic conditions - toxic, including alcoholic, viral, medicinal (during therapy with antibacterial agents, tricyclic antidepressants, antiviral, anti-tuberculosis and anticancer drugs, oral contraceptives);
- secondary encephalopathy;
- depressive syndrome, including secondary;
- withdrawal syndrome.
Contraindications
Absolute:
- bipolar disorder;
- age up to 18 years;
- I and II trimesters of pregnancy;
- lactation period;
- established hypersensitivity to the components of the drug.
Relative (taking Ademetionine requires special care and careful medical supervision):
- renal failure;
- combined treatment with herbal preparations, drugs containing tryptophan, tricyclic antidepressants (clomipramine), selective serotonin reuptake inhibitors;
- III trimester of pregnancy;
- elderly age.
Ademetionine, instructions for use: method and dosage
The solution prepared from the lyophilisate is intended for intravenous and intramuscular administration.
The drug is dissolved immediately before use in a specially supplied solvent. The rest of the lyophilisate is disposed of. It cannot be mixed with solutions containing calcium ions and alkaline solutions. If the porous mass is different from white with a yellowish tinge or almost white (due to heat or cracks in the vial), its use is not recommended.
When used intravenously, the solution is administered very slowly.
Therapy begins with intravenous or intramuscular injection based on the calculation of 5 to 12 mg per 1 kg of the patient's body weight per day.
Recommended dosage regimen:
- intrahepatic cholestasis: 400–800 mg per day (1–2 bottles) for 14 days;
- depression: 400–800 mg per day (1–2 bottles) for 15–20 days. If supportive treatment is needed, the drug continues to be used in tablet form at a dose of 800 to 1600 mg per day for 14–28 days.
The use of Ademetionine can be started both with i / v and i / m administration with further use in the form of tablets or immediately with the use of this dosage form.
No differences in the effectiveness of the drug in elderly patients compared with younger patients were found in clinical studies. However, taking into account the high risk of existing dysfunctions of the heart, liver or kidneys, other concomitant diseases or combined therapy with other drugs, the dose of the drug in the elderly is selected with caution, starting the use of the lyophilisate from the lower limit of the dose range.
Clinical data on the use of the substance in renal failure are limited, which is why medical supervision is required for its appointment in these cases.
Pharmacokinetic parameters of ademetionine in healthy individuals and in patients with chronic liver pathologies are similar.
Side effects
Diarrhea, nausea and headache were the most common adverse reactions in clinical trials of Ademetionine with more than 2,100 volunteers.
Possible adverse events (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare; the frequency cannot be determined from the available data - with unspecified frequency):
- infectious and parasitic pathologies: infrequently - urinary tract infections;
- immune system: infrequently - change in pulse rate (bradycardia, tachycardia) or blood pressure (arterial hypertension / hypotension), chest discomfort, back pain, bronchospasm, shortness of breath, anaphylactoid or anaphylactic reactions (including skin hyperemia), reactions increased sensitivity;
- psyche: often - insomnia, anxiety; infrequently - confusion, agitation;
- nervous system: often - headache; infrequently - dysgeusia, paresthesia, dizziness;
- vessels: infrequently - phlebitis, arterial hypotension, hot flashes;
- respiratory system, chest and mediastinal organs: infrequently - laryngeal edema;
- gastrointestinal tract: often - nausea, diarrhea, abdominal pain; infrequently - vomiting, gastrointestinal upset, gastrointestinal bleeding, pain in the gastrointestinal tract, flatulence, indigestion, dry mouth; rarely - esophagitis, bloating;
- skin and subcutaneous tissue: often - itchy skin; infrequently - skin-allergic reactions (including erythema, urticaria, skin rash and itching), angioedema, increased sweating;
- musculoskeletal and connective tissue: infrequently - muscle spasms, arthralgia;
- general disorders and disorders at the injection site: infrequently - chills, fever, edema, asthenia, reactions and skin necrosis at the injection site; rarely - malaise.
Overdose
There are no data on ademetionine overdose.
special instructions
Taking into account the tonic effect of the drug, it is not recommended to take it before bedtime. When it is prescribed to patients with cirrhosis of the liver against the background of hyperazotemia, it is important to systematically control the nitrogen content in the blood. Long-term therapy should be accompanied by periodic determination of serum creatinine and urea levels.
Ademetionine 400 mg is not recommended for patients with bipolar disorder. There are reports of the transition of depression to hypomania or mania against the background of its use. With depression, the likelihood of suicide and other serious side effects is increased, and therefore, during the period of therapy, such patients should be under constant medical supervision in order to assess and treat the manifestations of depression. Patients should be informed about the need to inform the doctor about the absence of improvement or worsening of the condition during the period of use of the lyophilisate. It has also been reported about the sudden onset or escalation of anxiety with its use. Usually, treatment withdrawal is not required, in several cases the anxiety disappeared after lowering the dose or stopping the use of the drug.
Since the content of the drug may decrease against the background of a deficiency of folic acid and cyanocobalamin, in patients at risk (during pregnancy, liver disease, anemia, or if there is a risk of vitamin deficiency due to pathology or adherence to a diet, for example, in vegetarians), the content should be monitored vitamins in blood plasma. If their deficiency is found before or during therapy with Ademetionine, it is recommended to take cyanocobalamin and folic acid.
It should be borne in mind that in an immunological analysis, the use of a solution may lead to a false determination of an indicator of a high homocysteine content in the blood. In this regard, it is recommended to use other methods of analysis to determine the concentration of homocysteine.
The composition of 1 dose of Ademetionine contains less than 23 mg (1 mmol) of sodium, that is, it practically does not contain this element.
Influence on the ability to drive vehicles and complex mechanisms
During the period of therapy with Ademetionine, dizziness may develop, and therefore driving vehicles, as well as performing other work related to increased attention, is prohibited until the patient is sure that therapy does not affect his ability to engage in this kind of activity.
Application during pregnancy and lactation
Ademetionine is not recommended for administration in the first and second trimesters of pregnancy. In the third trimester, caution is required when taking the drug.
If it is necessary to use the drug during lactation, breastfeeding is stopped.
Pediatric use
The use of Ademetionine in children and adolescents under the age of 18 is contraindicated, since the safety and efficacy profile of its use in patients of this age group has not been sufficiently studied.
With impaired renal function
Renal failure is a relative contraindication to the appointment of Ademetionine.
Use in the elderly
In elderly patients, treatment is recommended with caution.
Drug interactions
No interactions of ademetionine with other substances / preparations have been established. The development of serotonin excess syndrome has been reported against the background of combined treatment with Ademetionine and clomipramine (in such cases, it is recommended to be careful).
Analogs
Analogs of Ademetionine are Samelix, Ademetionine-Vial, Heptral, Heparetta, Heptrazan, Heptor, Heptor N, etc.
Terms and conditions of storage
Store at temperatures up to 25 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Ademetionine
There are few reviews about Ademetionine, indicating its effectiveness.
Price for Ademetionine in pharmacies
The price of Ademetionine 400 mg is unknown because it is not available in pharmacies. The approximate cost of drug analogues (all drugs contain 5 ampoules with 400 mg of lyophilisate in a package for preparing a solution for intravenous and intramuscular administration in each ampoule and a solvent): Heptral - 1560-1955 rubles, Samelix - 1309-1379 rub., Heptor - 1055-1566 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, 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!
