Heptral, 400 mg 20 pcs

Pharmacotherapeutic group Other drugs for gastrointestinal tract and metabolism, amino acids and their derivatives

ATC code A16AA02

Pharmacological properties.

Pharmacodynamic

Ademetionine belongs to the group of hepatoprotectors, also has antidepressant activity. It has choleretic and cholokinetic effect, has detoxifying, regenerating, antioxidant, antifibrotic and neuroprotective properties.

It replenishes the S-adenosyl-L-methionine (ademetionine) deficiency and stimulates its production in the body, contained in all body fluids. The highest concentration of ademetionine is found in the liver and brain. Ademetionine plays a key role in the metabolic processes of the body and takes part in major biochemical reactions: transmethylation, transsulfurization and transamination.

In transmethylation reactions ademetionine donates methyl groups for the synthesis of cell membrane phospholipids, neurotransmitters, nucleic acids, proteins, hormones and others. In transsulfurization reactions ademetionine is a precursor of cysteine, taurine, glutathione (providing redox mechanism of cellular detoxification), coenzyme A (is included into biochemical reactions of tricarboxylic acid cycle and fills the cell energy potential).

Increases glutamine content in the liver, plasma cysteine and taurine, decreases methionine content in the serum, normalizing metabolic reactions in the liver. After decarboxylation it participates in aminopropylation reactions as a precursor of polyamines – putrescine (promoter of cell regeneration and hepatocyte proliferation), spermidine and spermin, included in the structure of ribosomes, which reduces the risk of fibrosis.

It has choleretic action. Ademetionine normalizes the synthesis of endogenous phosphatidylcholine in hepatocytes, which increases membrane fluidity and polarization. This improves the function of bile acid transport systems associated with membranes of hepatocytes and contributes to bile acid passage to biliary tracts.

Effective with intradolocular variant of cholestasis (disorders of bile synthesis and flow). Ademetionine reduces the toxicity of bile acids in the hepatocyte by performing their conjugation and sulfation. Conjugation with taurine increases solubility of bile acids and their excretion from the hepatocyte. The process of sulfation of bile acids promotes 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 liver cell membranes from toxic effects of nonsulfated bile acids (in high concentrations present in hepatocytes with intrahepatic cholestasis).

In patients with diffuse liver diseases (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome, ademetionine reduces the severity of skin itching and changes of biochemical parameters, including the concentration of direct bilirubin, alkaline phosphatase activity, aminotransferases and others. Choleretic and hepatoprotective effect persists up to 3 months after discontinuation of treatment. It is shown to be effective in hepatopathies caused by various hepatotoxic drugs. Antidepressant activity appears gradually from the end of the first week of treatment and stabilizes during 2 weeks of treatment.

Several studies have confirmed the effectiveness of ademetionine in treatment of increased fatigability in patients with chronic liver disease. A pooled analysis of data from patients with pre-treatment symptoms of fatigue proved the effect of ademetionine treatment in reducing symptoms of increased fatigue in conjunction with a number of other symptoms, such as depression, hiccuria of the skin and mucous membranes, malaise and skin itching.

Ademetionine treatment significantly improved mood in patients with alcoholic liver disease who had a simultaneous positive response from symptoms of increased fatigue. In addition, in patients with alcoholic liver disease and nonalcoholic fatty liver disease with achieved response to ademetionine treatment on the side of fatigue symptoms there was also observed a significant reduction in such symptoms as acidity of the skin and mucous membranes, malaise and skin itching.

Indications

Alcoholism, Hepatitis, liver damage, liver cirrhosis, cholecystitis

• Auxiliary therapy for established chronic liver disease, to improve and maintain its function.
• Elevated fatigue in established chronic liver disease.

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Active ingredient

Ademetionine

Composition

Each tablet contains:

Active ingredient:

Ademetionine (Active ingredient dosage: 400 mg)

Excipients: colloidal silica – 4.4 mg, microcrystalline cellulose – 93.6 mg, sodium carboxymethyl starch (type A) – 17.6 mg, magnesium stearate – 4.4 mg;

Tablet shell: methacrylic acid and ethyl acrylate copolymer (1:1) – 27.6 mg, macrogol-6000 – 8.07 mg, polysorbate-80 – 0.44 mg, simethicone (emulsion 30%) – 0.13 mg, sodium hydroxide – 0.36 mg, talc – 18.4 mg, water – Q.S.

How to take, the dosage

– The recommended dose is 10-25 mg of ademetionine per 1 kg of body weight per day. Usually the daily dose is 1-2 tablets per day (from 400-800 mg of ademetionine per day) and may be increased to 4 tablets per day (up to 1600 mg of ademetionine per day).

– Heptral tablets^® 400 mg should be taken whole, without chewing, preferably in the morning between meals. Heptral tablets ^{® 400 mg should be taken out of the blister immediately before drinking because ademetionine, the active ingredient of Heptral ®, is sensitive to light.}

Age for use: From 18 years of age.

Interaction

No known interactions with other drugs have been observed.

There is a report of serotonin excess syndrome in a patient taking ademetionine and clomipramine. It is believed that this interaction is possible and ademetionine should be prescribed with caution together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), and herbs and drugs containing tryptophan.

Special Instructions

Taking into account the tonic effect of the drug, it is not recommended to take it before going to bed. When using Heptral® by patients with liver cirrhosis against hyperazotemia background, systematic monitoring of blood nitrogen content is required. During long-term therapy it is necessary to determine the serum urea and creatinine content.

There are reports about the conversion of depression into hypomania or mania in patients taking Ademetionine.

Patients with depression have an increased risk of suicide and other serious adverse events, so such patients should be under constant medical supervision during ademetionine treatment for evaluation and treatment of depression symptoms. Patients should inform the doctor if their symptoms of depression do not decrease or worsen during ademetionine therapy.

There are also reports of the sudden appearance or increase in anxiety in patients taking ademetionine. In most cases it is not required to cancel the therapy, in a few cases the anxiety disappeared after reducing the dose or canceling the drug.

Since cyanocobalamin and folic acid deficiency may decrease the content of ademetionine in patients at risk (with anemia, liver disease, pregnancy or the possibility of vitamin deficiency due to other diseases or diet, such as vegetarians), the plasma vitamin content should be controlled.

If insufficiency is detected, cyanocobalamin and folic acid administration prior to ademetionine treatment or concomitant administration with ademetionine is recommended.

In immunological testing, the use of ademetionine may contribute to the false detection of high blood homocysteine.

For patients taking ademetionine, it is recommended to use non-immunological testing methods to determine homocysteine content.

Influence on the ability to drive and operate machinery

In some patients dizziness may occur while taking Heptral®. It is not recommended to drive a vehicle or operate machinery while taking this medicine until the patient is sure that the therapy does not affect the ability to perform this type of activity.

Synopsis

Intestine-soluble film-coated tablets, white to white with a yellowish tint, oval, biconvex.

Heptral^® is a source of active amino acid, which is involved in more than 100 vital reactions in the liver. Heptral^® triggers the process of natural liver cell repair from within, working in several ways at once:

– Restoring cell structure: participates in the synthesis of building components of the cell wall.

– Excretion of toxins: provides the redox mechanism of cellular detoxification as a precursor of glutathione, the most active antioxidant of the liver.

– Bile acid excretion: improves the function of transport channels and promotes the transport of bile acids into the biliary tract.

– Replenishment of cells energy potential: participates in the synthesis of energy molecules in the mitochondria of liver cells.

– Regeneration of liver cells: stimulates the “multiplication” of healthy liver cells, helping liver repair.

The intake of Heptral^® also helps reduce the increased fatigue that often accompanies patients with chronic liver disease. Already after the 1st week of use Heptral^® helps restore liver function, reducing fatigue signals and restoring vigor.

Heptral^® tablets 400 mg easy to take: can be taken once a day, between meals. The effects of taking Heptral^® can last for 3 months after the end of treatment.

Contraindications

Genetic disorders that affect the methionine cycle, and/or cause homocystinuria and/or hyperhomocysteinemia (cystathionine betasynthase deficiency, disorder of vitamin B12 metabolism).

Hypersensitivity to any of the drug components.

Age under 18 years (experience of medical use in children is limited).

Bipolar disorders.

With caution:

Pregnancy (first trimester) and the period of breastfeeding (use is possible only if the potential benefit to the mother exceeds the possible risk to the fetus or baby).

Simultaneous use with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (such as clomipramine), and herbal and tryptophan preparations.

Elderly age.

Renal insufficiency.

Side effects

The digestive system: frequently – nausea, abdominal pain, diarrhea; rarely – vomiting, dry mouth, esophagitis, dyspepsia, flatulence, gastrointestinal pain, gastrointestinal bleeding, liver colic.

Nervous system: rare – confusion, insomnia, dizziness, headache, paresthesia.

Musculoskeletal system: rare – arthralgia, muscle cramps.

Urinary system: rare – urinary tract infections.

Skin: rare – hyperhidrosis, itching, skin rash.

Local reactions: rare – reactions at the injection site, very rare – reactions at the injection site, necrosis of the skin at the injection site.

Allergic reactions: rare – anaphylactic reactions, very rare – Quincke’s edema, laryngeal edema.

Other: rare – flushes, superficial phlebitis, asthenia, chills, flu-like symptoms, weakness, peripheral edema, hyperthermia.

Overdose

Overdose of Heptral® is unlikely. In case of overdose, observation of the patient and symptomatic therapy are recommended.

Pregnancy use

It has been shown in clinical trials that the use of Ademetionine in the third trimester of pregnancy did not cause any undesirable effects. The use of Heptral® in pregnant women in the first trimester and during breastfeeding is possible only if the potential benefit to the mother exceeds the possible risk to the fetus or child

Similarities

Heptor, Samelix