Regepaton^® (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Diamed-Pharma, LLC (Russia)

Manufactured By

Deko Company, LLC (Russia)

ATC Code

A16AA02 (Ademetionine)

Active Substance

Ademetionine (Rec.INN registered by WHO)

Dosage Form

Regepaton®

Lyophilizate for preparation of solution for intravenous and intramuscular administration 400 mg

Dosage Form, Packaging, and Composition

Lyophilizate for preparation of solution for intravenous and intramuscular administration

760 mg – vials (30 pcs.) – cardboard packs /in a kit with solvent (ampoules) 5 ml -30 pcs./ – By prescription
760 mg – vials (5 pcs.) – cardboard packs /in a kit with solvent (ampoules 5 ml) – 5 pcs./ – By prescription
760 mg – vials (50 pcs.) – cardboard packs /in a kit with solvent (ampoules) 5 ml -50 pcs./ – By prescription

Clinical-Pharmacological Group

Hepatoprotective agent. Drug with antidepressant activity

Pharmacotherapeutic Group

Other preparations for the gastrointestinal tract and metabolism, amino acids and their derivatives

Pharmacological Action

Hepatoprotector, has antidepressant activity. It has a choleretic and cholekinetic effect. It possesses detoxifying, regenerating, antioxidant, antifibrotic and neuroprotective properties.

It replenishes the deficiency of ademetionine and stimulates its production in the body, primarily in the liver and brain. It participates in biological transmethylation reactions (methyl group donor) – the molecule of S-adenosyl-L-methionine (Ademetionine) is a methyl group donor in the methylation reactions of phospholipids of cell membranes, proteins, hormones, neurotransmitters; it participates in transsulfuration reactions as a precursor of cysteine, taurine, glutathione (provides the redox mechanism of cellular detoxification), coenzyme of acetylation. It increases the content of glutamine in the liver, cysteine and taurine in plasma; it reduces the content of methionine in serum, normalizing metabolic reactions in the liver. In addition to 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, resulting from the stimulation of phosphatidylcholine synthesis in them. This improves the function of the bile acid transport systems associated with hepatocyte membranes and promotes the passage of bile acids into the biliary system. It is effective in the intralobular variant of cholestasis (impaired synthesis and flow of bile). It promotes the 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 makes possible their elimination by the kidneys, facilitates passage through the hepatocyte membrane and excretion with bile. In addition, sulfated bile acids protect liver cell membranes from the toxic effects of non-sulfated bile acids (present in high concentrations in hepatocytes in intrahepatic cholestasis). In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, it reduces the severity of skin itching and changes in biochemical parameters, including the level of direct bilirubin, activity of alkaline phosphatase, aminotransferases.

Pharmacokinetics

After a single oral dose of 400 mg, the C_max of ademetionine in plasma is reached after 2-6 hours and is 0.7 mg/l. The bioavailability of the drug when taken orally is 5%, with intramuscular administration – 95%.

Binding to serum proteins is insignificant.

It penetrates the blood-brain barrier. Regardless of the route of administration, a significant increase in the concentration of ademetionine in the cerebrospinal fluid is noted. It is metabolized in the liver. T_1/2 – 1.5 hours. It is excreted by the kidneys.

Indications

Intrahepatic cholestasis in precirrhotic and cirrhotic conditions, including: fatty liver dystrophy; chronic hepatitis; toxic liver lesions of various etiologies, including alcoholic, viral, drug-induced (antibiotics, antitumor, antituberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives); chronic acalculous cholecystitis; cholangitis; liver cirrhosis; encephalopathy, including that associated with hepatic insufficiency (including alcoholic).

Intrahepatic cholestasis in pregnant women.

Symptoms of depression.

ICD codes

Dosage Regimen

It is used orally, intramuscularly or intravenously (very slowly).

When taken orally, the daily dose is 800-1600 mg.

With intravenous or intramuscular administration, the daily dose is 400-800 mg.

The duration of treatment is set individually depending on the severity and course of the disease.

In elderly patients, treatment is recommended to start with the lowest recommended dose, taking into account the reduction in liver, kidney or heart function, the presence of concomitant pathological conditions and the use of other drugs.

Adverse Reactions

From the digestive system frequently – nausea, abdominal pain, diarrhea; rarely – vomiting, dry mouth, esophagitis, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, hepatic colic.

From the nervous system rarely – confusion, insomnia, dizziness, headache, paresthesia.

From the musculoskeletal system rarely – arthralgia, muscle cramps.

From the urinary system rarely – urinary tract infections.

From the skin rarely – hyperhidrosis, itching, skin rash.

Local reactions rarely – reactions at the injection site; very rarely – reactions at the injection site, skin necrosis at the injection site.

Allergic reactions rarely – anaphylactic reactions; very rarely – Quincke’s edema, laryngeal edema.

Other: rarely – hot flashes, superficial phlebitis, asthenia, chills, flu-like symptoms, weakness, peripheral edema, hyperthermia.

Contraindications

Genetic disorders affecting the methionine cycle, and/or causing homocystinuria and/or hyperhomocysteinemia (cystathionine beta-synthase deficiency, cyanocobalamin metabolism disorder); age under 18 years, hypersensitivity to ademetionine.

Use in Pregnancy and Lactation

In the I and II trimesters of pregnancy, Ademetionine is used only in case of extreme necessity, when the expected benefit to the mother outweighs the potential risk to the fetus. The use of ademetionine in high doses in the III trimester of pregnancy did not cause any adverse effects.

The use of ademetionine during breastfeeding is possible only if the expected benefit to the mother outweighs the potential risk to the child.

Use in Hepatic Impairment

The drug is approved for use in liver dysfunction

Pediatric Use

Contraindication: children and adolescents under 18 years of age.

Special Precautions

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.

Deficiency of vitamin B₁₂ and folic acid can lead to a decrease in ademetionine concentrations, so their concomitant use in usual doses is recommended.

Patients with depression require careful monitoring and constant psychiatric care when treated with ademetionine in order to control the effectiveness of treatment.

When used in patients with liver cirrhosis against the background of hyperazotemia, systematic monitoring of blood nitrogen levels is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.

Effect on the ability to drive vehicles and mechanisms

When using ademetionine, dizziness is possible. Patients should not drive vehicles or work with other mechanisms until the symptoms that may affect the speed of reaction in these activities have completely disappeared.

Drug Interactions

There is a report of the development of serotonin syndrome in a patient using Ademetionine and clomipramine.

Ademetionine should be used with caution simultaneously with selective serotonin reuptake inhibitors, tricyclic antidepressants, drugs and herbal remedies containing tryptophan.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.