HEPARD [Ademetionine] 500 mg Powder for solution for IV, IM administration
instructions
for the medical use of the medicinal product
HEPARD
Tradename Hepard, Хепард
International non-proprietary name
or generic name
Ademethionine, Адеметионин
Состав
Each
vial of powder contains: ademetionine 1,4-butanedisulfonate 500 mg
Each ampoule of solvent contains: lysine
hydrochloride 425 mg, sodium hydrochloride, water for injection.
Dosage form
Powder
for preparation of solution with solvent.
Pharmacotherapeutic
group
Metabolic
agent, Hepatoprotector, Vitamins.
Pharmacological properties
Pharmacodynamics
Ademetionine belongs to the
group of hepatoprotectors, and also has antidepressant activity. It has a
choleretic and cholekinetic effect. It has detoxifying, regenerating,
antioxidant, antifibrotic and neuroprotective properties. It replenishes the
deficiency of S-adenosyl-L-methionine (ademetionine) and stimulates its
production in the body, it is found in all body environments. The highest
concentration of ademetionine is noted in the liver and brain. It plays a key
role in the metabolic processes of the body, participates in important
biochemical reactions: transmethylation, transsulfuration, 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 transsulfuration reactions of ademetionine, it is a precursor
of cysteine, taurine, glutathione (ensuring the oxidation-reduction mechanism
of cellular detoxification), coenzyme A (included in biochemical reactions of
the tricarboxylic acid cycle and replenishes the energy potential of the cell).
Increases the content of
glutamine in the liver, cysteine and taurine in plasma; reduces
the content of methionine in serum, normalizing metabolic reactions in the
liver. After decarboxylation, it participates in aminopropylation processes as
a precursor of polyamines - putrescine (a stimulator of cell regeneration and
proliferation of hepatocytes), spermidine and spermine, which are part of the
structure of ribosomes, which reduces the risk of fibrosis.
Has a choleretic effect.
Ademetionine normalizes the synthesis of endogenous phosphatidylcholine in
hepatocytes, which increases 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. It is
effective in intralobular cholestasis (impaired synthesis and flow of bile).
Ademetionine reduces the toxicity of bile acids in the hepatocyte by
conjugating and sulfating them. Conjugation with taurine increases the
solubility of bile acids and their excretion from the hepatocyte. The process
of bile acid sulfation facilitates their elimination by the kidneys,
facilitates their passage through the hepatocyte membrane and excretion with
bile. In addition, sulfated bile acids themselves additionally protect liver
cell membranes from the toxic effect 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, ademetionine reduces the severity of skin itching and changes in
biochemical parameters, including the concentration of direct bilirubin,
alkaline phosphatase activity, aminotransferases, etc. The choleretic and
hepatoprotective effect lasts up to 3 months after stopping treatment.
Efficiency has been shown in
hepatopathies caused by various hepatotoxic drugs.
Antidepressant activity
appears gradually, starting from the end of the 1st week of treatment, and
stabilizes within 2 weeks of treatment.
Pharmacokinetics
Parenteral bioavailability is
96%, Cmax in plasma is achieved after 45 minutes.
Plasma protein binding is
insignificant, ≤ 5%. Penetrates the BBB. A significant increase in the
concentration of ademetionine in the cerebrospinal fluid is noted.
Metabolized in the liver. The
process of formation, consumption and re-formation of ademetionine is called
the ademetionine cycle. In the first stage of this cycle,
ademetionine-dependent methylases use ademetionine as a substrate for the production
of S-adenosylhomocysteine, which is then hydrolyzed to homocysteine and adenosine by S-adenosylhomocysteine hydrolase. Homocysteine, in turn, undergoes reverse
transformation to methionine by transferring a methyl group from
5-methyltetrahydrofolate. As a result, methionine can be converted to
ademetionine, completing the cycle. T1/2 - 1.5 h. Excreted by the kidneys.
Indications for use
• intrahepatic cholestasis in
precirrhotic and cirrhotic conditions, which can be observed in the following
diseases:
• fatty liver disease;
• chronic hepatitis;
• toxic liver damage of
various etiologies, including alcoholic, viral, medicinal (antibiotics,
antitumor, antituberculosis and antiviral drugs, tricyclic antidepressants,
oral contraceptives);
• chronic acalculous
cholecystitis;
• cholangitis;
• liver cirrhosis;
• encephalopathy, including
that associated with liver failure (including alcoholic);
• intrahepatic cholestasis in
pregnant women;
Contraindications
• hypersensitivity to any of
the components of the drug;
• genetic disorders affecting
the methionine cycle and/or causing homocystinuria and/or hyperhomocysteinemia
(cystathionine beta-synthase deficiency, cyanocobalamin metabolism disorder);
• bipolar disorders;
• age under 18 years.
With caution.
First trimester of pregnancy and breastfeeding period (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. Elderly age. Renal
failure.
Method of administration
and dosage
It is used intravenously and
intramuscularly. The dose and duration of treatment are determined individually
by the doctor, taking into account the patient's condition, age and other
diseases.
Before use, the lyophilisate
for intramuscular and intravenous administration should be dissolved using the
supplied solvent. The remainder of the drug should be disposed of. The
appropriate dose of the drug for intravenous administration should then be
dissolved in 250 ml of physiological solution or 5% glucose solution and
administered slowly over 1-2 hours.
The drug should not be mixed
with alkaline solutions and solutions containing calcium ions.
Initial therapy: The
recommended dose is 5-12 mg/kg/day IV or IM.
The
recommended daily dose is 500 to 1000 mg. The usual duration of therapy is 14
days.
If
maintenance therapy is necessary, it is recommended to continue taking the drug
in tablet form.
Special instructions and precautions
Before use, consult a doctor.
When using the drug in patients with
liver cirrhosis against the background of hyperazotemia, it is necessary to
systematically monitor the nitrogen content in the blood. During long-term
therapy, it is necessary to determine the content of urea and creatinine in the
blood serum.
Since a deficiency of cyanocobalamin
and folic acid 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 deficiency is
detected, it is recommended to take cyanocobalamin and folic acid before
starting treatment with ademetionine or simultaneously with ademetionine.
In immunological analysis, the use
of ademetionine can contribute to a false determination of the indicator of
high homocysteine in the blood. For patients taking
ademetionine, it is recommended to use non-immunological analysis methods to
determine the level of homocysteine.
Influence on the ability to drive
vehicles and mechanisms
Dizziness may occur. It is not recommended to drive a
car or operate machinery while taking the drug until the patient is sure that
the therapy does not affect the ability to engage in such activities.
Interaction with other medicinal
products
There are currently no known cases
of interaction.
There is a report of serotonin
excess syndrome in a patient taking ademetionine and clomipramine. It is
believed that such an interaction is possible and caution should be exercised
when prescribing ademetionine together with SSRIs, tricyclic antidepressants
(such as clomipramine), as well as herbal remedies and drugs containing
tryptophan.
Side effect
From the digestive system: nausea,
vomiting, diarrhea, abdominal pain.
From the nervous system: dizziness,
headache, anxiety, insomnia.
From the cardiovascular
system: decreased blood pressure, hot flashes, phlebitis.
Allergic reactions: rash,
itching, urticaria, increased sweating.
Other: excessive
salivation, fishy body odor.
If any of the side effects
listed in the instructions worsen, or you notice any other side effects not
listed in the instructions, tell your doctor.
An
overdose of Hepard is unlikely. In case of overdose, patient observation and
symptomatic therapy are recommended.
Storage conditions
Store in a dry place
at a temperature not exceeding 250C.
Keep out of reach of
children.
Shelf life
2 years. Do not use
after the expiration date stated on the package.
Vacation
conditions
Dispensed by
prescription.
Release
form
1 bottle with powder for solution preparation and 1 ampoule with 5 ml solvent. 5 bottles and 5 ampoules together with instructions for use in a cardboard box.