Heptral dropper instructions for use. Heptral: ampoules and tablets, reviews, cheaper analogues

Latin name: Heptral
ATX code: A16A A02
Active substance: ademetionine
Manufacturer: ABBOTT Lab., (Germany),
AbbVie, Hospira (Italy)
Vacation from the pharmacy: on prescription
Storage conditions: at temperatures up to 25°C
Best before date: 3 y.

Heptral is a hepatoprotective medication with an antidepressant effect.

Indications for use are pathological conditions liver:

• Intrahepatic cholestasis (including during pregnancy)
• Toxic damage to the liver (due to intoxication with alcohol, drugs, viral and other infections)
• Acalculous cholecystitis in chronic form
• cirrhosis
• Cholangitis
• Encephalopathy
• Manifestations of depression.

The composition of the drug

Heptral tablets

• Active: 400 or 500 mg of ademetionine
• Additional: aerosil, CMK, sodium KMK (t. A), E 572
• Enteric coating: copolymer of methacrylic acid and ethyl acrylate, macrogol-6000, polysorbate, simethicone emulsion, sodium hydroxide, talc.

Ellipsopod tablets, food-grade, white to pale yellow. Packed in 10 pieces in blisters. In the box - 1-2 plates, an accompanying description.

Heptral injections

• In 1 vial: 400 mg ademetionine
• In 1 amp. solvent: L-lysine, sodium hydroxide, water.

Medicines in the form of a concentrate for reconstitution of injection solution: lyophilisate without foreign inclusions and suspensions, white or yellowish tint. The solvent is a translucent clear liquid. May be uncolored or pale yellow. The reconstituted injection liquid is clear, uncolored or slightly yellowish, without suspensions. The concentrate is packaged in bottles of uncolored glass (vol. 1) of 5 ml, the solvent - 5 ml in ampoules. Both funds are invested in cell packs of 5 pcs. The box contains 5 vials and ampoules, an accompanying annotation.

Medicinal properties

Price: 400 mg (10 pcs) - 1626 rubles, (20 pcs) - 1552 rubles, 500 mg (20 pcs) - 2003 rubles.

The therapeutic effect of Heptral is explained by the properties of the main component - ademetionine. The substance exhibits the qualities of a hepatoprotector: it has detoxifying, antioxidant, neuroprotective and regenerating effects.

After penetration, it eliminates the lack of ademetionine in the body and activates internal processes for its synthesis. Accelerates metabolic processes and increases the level of glutamine in the liver, plasma amino acids, reduces the serum concentration of methionine.

The choleretic effect is achieved by increasing motility and improving the membranes of hepatocytes, activating the synthesis of enzymes. This enhances transport fatty acids and their excretion into the bile ducts.

The beneficial effect of the drug for the liver lies in the fact that with cirrhosis and hepatitis it reduces the intensity of skin itching, changes the activity of alkaline phosphatase, bilirubin, etc.

After ingestion, the drug forms a peak plasma concentration level after 2-6 hours. Bioavailability after parenteral administration is 95%, after oral forms - 5%. The substance passes through the BBB, forms a strong concentration in spinal cord. Biotransformed in the liver, excreted from the body by the kidneys. The half-life is about one and a half hours.

Mode of application

Therapy can begin at the discretion of the doctor - with the use of the drug Heptral in ampoules, followed by transfer of the patient to oral form or immediately after taking the pills. The instructions for use recommend dividing the total daily dosage into several doses (usually 2-3 times).

Tablets

The medicine is taken orally as a whole, without chewing, preferably before lunchtime in the interval between meals. Pills should be taken out of the package immediately before use, while it is important to pay attention to the condition of the shell - if the coating differs in shade from that declared by the manufacturer (white or pale yellow), then the tablets are considered spoiled.

• With intrahepatic cholestasis, depression therapy, the daily amount is 800-1600 mg.

Heptral injection

Initial treatment: the method of application is determined by the doctor, since Heptral is used intravenously or injected intravenously. The recommended starting dosage per day is 400 mg. The solution is prepared immediately before administration. It is highly undesirable to restore the medication in advance, since the drug may lose its medicinal properties.

The duration of the course Heptral intramuscularly (or intramuscularly) is determined on an individual basis. Manufacturers recommend using drugs for the treatment of depression from 15 to 20 days, liver pathologies - about two weeks. After completing the course of injections, the patient, if necessary, is transferred to tablets.

To prepare the medicine for injections, the contents of the vial are combined with the solvent from the ampoule, making sure that the containers with the lyophilizate and the solvent are intact. Then the desired dosage of the drug is mixed with saline or glucose (5%) solution. Droppers are recommended to be placed for 1-2 hours. The remaining liquid must be disposed of.

The reconstituted Heptral solution cannot be combined with alkaline preparations and liquids containing calcium ions.

At-risk groups

Clinical studies of the effect of the drug on the body of aged patients did not reveal significant differences compared to younger patients. Nevertheless, it is recommended to approach dosing with the utmost care. At the beginning of the course, it is desirable to assign minimum medicinal dosages the drug Heptral, and it is possible to increase the daily amount only after an analysis of tolerability.

If the patient suffers from liver / kidney dysfunctions, then drugs should also be used with increased caution.

Children

The drug is not used in pediatrics due to the lack of sufficient experience in treatment.

Special instructions for use

Some patients may experience dizziness after taking ademetionine. In such cases, you need to be careful when driving a car, complex devices, and also refrain from any type of activity in which there is a risk to health and life.

Since Heptral has tonic properties, the medicine should be used in the first part of the day.

If Heptral is prescribed to a patient with liver diseases (especially with cirrhosis), then during the course it is necessary to regularly check the level of nitrogen concentration in the body, with a long course - the saturation of serum with urea and creatinine.

It is undesirable to prescribe the drug to patients suffering from bipolar disorders, since there is a high risk of depression with its subsequent transition to a manic state.

Patients receiving Heptral in the treatment of depression are particularly susceptible to suicide. For this reason, such patients should be under close medical supervision. In addition, patients should immediately inform doctors if the medication does not reduce the manifestations of depression, or if the disease progresses.

AT clinical practice there are reports that the drug can provoke increased anxiety. Usually, discontinuation of treatment is not required, since side effects stopped after dosage reduction.

Because with a lack of vit. B12 and folic acid in patients at risk may decrease the level of ademetionine, then at the time of therapy it is necessary to constantly monitor the content of vitamins in the body. If the analyzes revealed their deficiency, then before the start of the treatment course and during it, an additional course of vitamin therapy is required.

When conducting laboratory tests, it must be taken into account that ademetionine can distort their results.

During pregnancy and HB

The use of high dosages of Heptral 400 mg in the 3rd trimester of gestation did not provoke a negative reaction of the body. For more early dates(1 and 2 tr.) the use of Heptral during pregnancy is allowed after a detailed study of the ratio of benefits for the pregnant woman and the threat of complications in the fetus.

The combination of treatment and lactation should be considered by the attending physician.

Contraindications and precautions

Average price: 1678 rubles.

Heptral in any pharmaceutical form is prohibited for use with:

• Individual hypersensitivity to any of the constituent ingredients of the drug
• Genetic pathologies that affect the methionine cycle or contribute to the occurrence of a lack of cystathionine β-synthase in the body, a disorder of metabolic processes vit. AT 12
• Under the age of 18 years (due to limited experience in patients of this category).

Conditions in which the use of the drug requires high precautions:

• Bipolar disorders
• 1st trimester of pregnancy, GV
• Therapy with SSRIs, TCAs, herbal drugs and medicines with tryptophan
• Elderly age
• Kidney dysfunction.

Drug Interactions

No clinically significant reactions with other medications have been recorded.

There is evidence of the development of serotonin intoxication after patients took ademetionine simultaneously with clomipramine.

Care should be taken when complex treatment with SSRIs, TCAs, herbal remedies and drugs with tryptophan.

Side effects and overdose

The introduction of Heptral, like any drug, can provoke a negative reaction of the body in the form of adverse reactions. Most often, patients complain of headaches, diarrhea and nausea. But during therapy, there may be other undesirable phenomena:

• Gastrointestinal tract: abdominal pain, diarrhea, nausea (with or without vomiting), dryness of the mucous tissues of the mouth, dyspeptic conditions, flatulence, GI bleeding, indigestion, bloating, inflammation of the esophagus.
• General phenomena and reactions at the site of infusion: asthenia, swelling, heat, fever, local disorders, tissue necrosis in the injection area, general lethargy.
• Immune system: hypersensitivity reactions, anaphylaxis (fever, bronchospasm, apnea, chest tightness, hypo- or hypertension), increased heart rate.
• Urinary tract infections.
• Musculoskeletal system: joint pain, muscle cramps.
• Psyche: increased anxiety, sleep disorders, insomnia, in some patients - agitation, clouding of consciousness, suicidal manifestations, depression.
• Respiratory organs: swelling of the tissues of the larynx.
• Dermis and s / c layers: itching, severe sweating, Quincke's edema, rashes.
• Vessels: flushing, hypotension, inflammation of the veins.
• NS: dizziness, loss of sensation in certain parts of the body.

An overdose of Heptral is not expected. In clinical practice, reports of cases of intoxication with ademetioinine are rare. In the case of the development of pathological conditions after taking large doses of the drug, the patient should be hospitalized. Treatment is determined based on the condition of the victim - as a rule, symptomatic and supportive therapy is carried out.

Analogues

Possible substitutes for Heptral and analogues are allowed to be used only after visiting a doctor.

Veropharm (RF)

Price: tab. (20 pieces) - 986 rubles, (40 pieces) - 1758 rubles, liof. (5 vials + 5 amp. R-la) - 1268 rubles.

Drugs based on ademetionine, an analogue of Heptral in tablets and lyophilisate for injections. It is used for liver diseases and manifestations of depression.

The duration of the therapeutic course, the choice of pharmaceutical forms and dosage are determined separately in each case.

Pros:

• Heals the liver
• Accelerates the flow of bile
• It costs less than Heptral.

Flaws:

• Side effects.

Active substance: ademetionine 1,4-butanedisulfonate 760 mg (corresponding to 400 mg of ademetionine ion) in 1 ampoule

Release form

Lyophilisate in a colorless glass vial. Solvent 5 ml in glass ampoules. 5 bottles and 5 ampoules in a carton box.

pharmachologic effect

Ademetionine belongs to the group of hepatoprotectors, it also has antidepressant activity.

It has a choleretic and cholekinetic effect, has detoxifying, regenerating, antioxidant, antifibrosing and neuroprotective properties.

Indication for use

• Intrahepatic cholestasis in precirrhotic and cirrhotic conditions, which can be observed with the following diseases:
  • fatty degeneration of the liver;
  • 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;
  • cirrhosis of the liver;
  • encephalopathy, incl. associated with liver failure (alcoholic, etc.).
• Intrahepatic cholestasis in pregnant women.
• Symptoms of depression.

Methods of application and doses

Intravenously and intramuscularly.

The lyophilizate must be dissolved in a specially supplied solvent immediately before administration. The rest of the drug must be disposed of.

The drug must not be mixed with alkaline solutions and solutions containing calcium ions.

If the lyophilisate has a color other than almost white to white with a yellowish tinge (due to a crack in the vial or exposure to heat), the use of Heptral is not recommended.

The drug Heptral with intravenous use injected very slowly.

Therapy with Heptral can be started with intravenous or intramuscular injection followed by the use of the drug Heptral in the form of tablets or immediately after the use of the drug Heptral in the form of tablets.

Contraindications

• Genetic disorders affecting the methionine cycle and / or causing homocystinuria and / or hyperhomocysteinemia (deficiency of cystathionine beta synthase, impaired metabolism of cyanocobalamin);
• hypersensitivity to any of the components of the drug;
• under 18 years of age (experience medical use limited in children)

special instructions

Given the tonic effect of the drug, it is not recommended to take it at bedtime.

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

Patients with depression have an increased risk of suicide and other serious adverse events, therefore, during treatment with ademetionine, these 11 patients should be under constant medical supervision to assess and treat symptoms of depression. Patients should inform the doctor if their symptoms of depression do not decrease or worsen during ademetionine therapy.

There are also reports of a sudden onset or increase in anxiety in patients taking ademetionine. In most cases, discontinuation of therapy is not required; in a few cases, anxiety disappeared after dose reduction or discontinuation of the drug.

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 blood plasma should be monitored. If deficiency is detected, it is recommended to take cyanocobalamin and folic acid before starting treatment with ademetionine or concomitantly with ademetionine. In immunological analysis, the use of ademetionine can contribute to the false determination of an indicator of high blood homocysteine.

For patients taking ademetionine, it is recommended to use non- immunological methods analysis to determine the content of homocysteine. One bottle of the drug Heptral lyophilisate for the preparation of a solution for intravenous and intramuscular injection, 400 mg / 5 ml contains 6.61 mg of sodium, which is equivalent to the amount of sodium in 16.8 mg of table salt and is 0.3% of the recommended maximum daily intake of sodium for adult.

Some patients may experience dizziness when taking Heptral. It is not recommended to drive a car and work with mechanisms while taking the drug until patients are sure that the therapy does not affect the ability to engage in this type of activity.

Storage conditions

In a place protected from light at a temperature of 15 ° C to 25 ° C. Keep out of the reach of children.

Description of the dosage form

Release form, composition and packaging

Enteric coated tablets , filmy, from white to white with a yellowish tint, oval, biconvex.

Excipients: colloidal silicon dioxide - 4.4 mg, microcrystalline cellulose - 93.6 mg, sodium carboxymethyl starch (type A) - 17.6 mg, magnesium stearate - 4.4 mg.

Shell composition: copolymer of methacrylic acid and ethyl acrylate (1:1) - 27.6 mg, macrogol 6000 - 8.07 mg, polysorbate 80 - 440 mcg, simethicone (30% emulsion) - 130 mcg, sodium hydroxide - 360 mcg, talc - 18.4 mg, water - q.s.

10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.

Lyophilizate for the preparation of a solution for intravenous and intramuscular administration in the form of a mass from almost white to white with a yellowish tint, without foreign inclusions.

Solvent: L-lysine, sodium hydroxide, water for injections.

Vials (5) complete with a solvent (5 ml - amp. 5 pcs.) - packs of cardboard.

Clinical and pharmacological group

pharmachologic effect

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

Compensates for the deficiency of ademetionine and stimulates its production in the body, primarily in the liver and brain. Participates in biological transmethylation reactions (methyl group donator) - S-adenosyl-L-methionine molecule (ademetionine) donates a methyl group in methylation reactions of phospholipids of cell membranes, proteins, hormones, neurotransmitters; transsulfation - a precursor of cysteine, taurine, glutathione (provides a redox mechanism for cellular detoxification), acetylation coenzyme. 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 hepatocyte proliferation), spermidine and spermine, which are part of the structure of ribosomes.

It has a choleretic effect due to an increase in the mobility and polarization of hepatocyte membranes, due to stimulation of the synthesis of phosphatidylcholine in them. It improves the function of membrane-associated hepatocyte transport systems bile acids 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). Promotes 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 removal from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates passage through the membrane of the hepatocyte and excretion with bile. In addition, sulfated bile acids protect the membranes of liver cells from the toxic effects of non-sulfated bile acids (in high concentrations present in hepatocytes in intrahepatic cholestasis). In patients with diffuse diseases liver (cirrhosis, hepatitis) with intrahepatic cholestasis syndrome reduces the severity of skin itching and changes biochemical parameters, incl. level of direct bilirubin, activity of alkaline phosphatase, aminotransferases.

Choleretic and hepatoprotective effect persists up to 3 months after discontinuation of treatment.

Efficacy has been shown in hepatopathy caused by hepatotoxic drugs.

Prescribing the drug to patients with opioid addiction accompanied by liver damage leads to regression clinical manifestations abstinence, improvement of the functional state of the liver and processes of microsomal oxidation.

Antidepressant activity appears gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. The drug is effective in recurrent endogenous and neurotic depression resistant to amitriptyline. It has the ability to interrupt relapses of depression.

The purpose of the drug in osteoarthritis reduces the severity of pain, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.

Pharmacokinetics

Suction

The tablets are coated with a special coating that dissolves only in the intestine, due to which ademetionine is released into duodenum. After a single oral administration of 400 mg of the drug, Cmax 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 a / m administration - 95%.

Distribution

Serum protein binding is negligible.

Penetrates through the BBB. Regardless of the route of administration, there is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.

Metabolism

Biotransformed in the liver.

breeding

T 1/2 - 1.5 hours. Excreted with the kidneys.

Indications for the use of the drug

- chronic acalculous cholecystitis;

- cholangitis;

- intrahepatic cholestasis;

- toxic liver damage of various etiologies (including alcoholic, viral, drug / antibiotics, antitumor drugs, anti-tuberculosis and antiviral drugs, tricyclic antidepressants, oral contraceptives /);

- fatty degeneration of the liver;

- chronic hepatitis;

- cirrhosis of the liver;

- encephalopathy, incl. associated with liver failure (including alcohol);

- depression (including secondary);

- withdrawal syndrome (including alcohol).

Dosing regimen

Apply inside, in / m or in / in drip.

At intensive care in the first 2-3 weeks, the drug is prescribed intravenously (very slowly) or intramuscularly in a daily dose of 400-800 mg.

The lyophilized powder is dissolved only in the special supplied solvent (L-lysine solution).

At maintenance therapy the drug is prescribed orally in a daily dose of 800-1600 mg. The duration of maintenance therapy can average 2-4 weeks.

Tablets should be swallowed whole, without chewing, it is advisable to take them in the morning, between meals.

Side effect

From the side digestive system: gastralgia, dyspepsia, heartburn.

Others: allergic reactions.

Contraindications to the use of the drug

- I and II trimester of pregnancy;

- lactation period breastfeeding);

- age up to 18 years;

— hypersensitivity to the components of the drug.

The use of the drug during pregnancy and lactation

Application for violations of liver function

Used according to indications

Application for violations of kidney function

special instructions

Given the tonic effect of Heptral, it is not recommended to use it at bedtime.

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

The solution is prepared immediately before use; if the color of the lyophilized powder differs from the proper one - white, it is necessary to refrain from using it.

Overdose

There were no clinical cases of overdose.

drug interaction

famous drug interaction drug Heptral ® with others medicines was not observed.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life - 3 years.

The drug Heptral, produced by the Italian branch of the American chemical-pharmaceutical corporation Abbott, belongs to the group of hepatoprotectors and is used mainly for certain hepatic pathologies. Why "mainly"? The fact is that active substance heptral - ademetionine - also has antidepressant activity, therefore, among the indications for prescribing this drug, there is also depressive disorders. But still, the main therapeutic "path" of heptral is to protect the liver. And for this, the drug is provided with everything necessary, such as: choleretic, cholekinetic, regenerating, detoxifying, antifibrosing, antioxidant and neuroprotective properties. Ademetionine is a natural substance synthesized in the liver. It is widely present in all biological environments of the body (its highest content is noted in the liver and brain) and is involved in many metabolic processes, including the three most important: transmethylation, transsulfuration and aminopropylation. In transmethylation (remethylation) reactions, ademetionine "donates" its methyl group for the synthesis of membrane phospholipids, neurotransmitters, proteins, hormones, etc. In transsulfation reactions, it is a substrate for the formation of glutathione, cysteine, taurine, and acetylation coenzyme. Heptral, in turn, compensates for the lack of natural ademetionine and activates its reproduction in the body, increases the content of L-glutamine in the liver, cysteine ​​and taurine in the blood plasma, and normalizes hepatic metabolism. The drug increases the production of bile in the liver: it normalizes the formation of endogenous phosphatidylcholine in the liver cells, which increases the fluidity (mobility) and polarization of cell membranes. This favorably affects the transport systems of bile acids associated with the membranes of the liver cells and promotes the movement of the latter through the biliary system.

For this reason, heptral is successfully used for intrahepatic bile stasis. Ademetionine, along with ursodeoxycholic acid, is considered the most promising drug in terms of influencing key links in the pathogenesis of intrahepatic (intralobular and interlobular) cholestasis. Heptral has exhaustively proven its effectiveness in the treatment and prevention of hepatopathy associated with the use of hepatotoxic drugs. This has a special importance in the treatment of cancer patients, when discontinuation of the hepatotoxic drug significantly reduces the effectiveness of chemotherapy and, as a result, worsens the prognosis of life. The appointment of Heptral to opioid addicts with hepatopathy leads to a decrease in withdrawal symptoms, improved liver function and normalization of microsomal oxidation processes. Another unique hepatoprotector property of heptral is antidepressant. It begins to appear from the end of the first week of taking the drug, fully stabilizing within 2 weeks of pharmacotherapy. Heptral is effective in recurrent endogenous and neurotic depression resistant to amitriptyline.

Heptral is available in two dosage forms: tablets and lyophilisate for solution for intravenous and intramuscular administration. Tablets are recommended to be taken in the morning between meals. An important nuance: the tablets should be taken out of the package immediately before taking. The tightness of the package is a prerequisite for maintaining the quality of the medicinal product: if the color of the tablet differs from white (a slight yellowness is allowed), then the tightness has been broken and the drug can no longer be used for its intended purpose. A solution of heptral for intravenous and intramuscular administration is prepared immediately before administration using the solvent enclosed in the package. The rest of the drug must be disposed of.

Pharmacology

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

Compensates for the deficiency of ademetionine and stimulates its production in the body, is found in all environments of the body. The highest concentration of ademetionine was found in the liver and brain. It plays a key role in the metabolic processes of the body, takes part in important biochemical reactions: transmethylation, transsulfuration, transamination. In transmethylation reactions, ademetionine donates a methyl group for the synthesis of cell membrane phospholipids, neurotransmitters, nucleic acids, proteins, hormones, etc. 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 hepatocyte proliferation), spermidine and spermine, which are part of the ribosome structure, which reduces the risk of fibrosis.

It 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 bile acid transport systems associated with hepatocyte membranes and promotes the passage of bile acids into the biliary system. It is effective in intrahepatic (intralobular and interlobular) variant of 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 removal from the hepatocyte. The process of sulfation of bile acids contributes to the possibility of their elimination by the kidneys, facilitates passage through the membrane of the hepatocyte and excretion with bile. In addition, sulfated bile acids themselves additionally protect the membranes of liver cells from the toxic effects of non-sulfated 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 pruritus and changes in biochemical parameters, incl. level of direct bilirubin, activity of alkaline phosphatase, aminotransferases. Choleretic and hepatoprotective effect persists up to 3 months after discontinuation of treatment.

Efficacy has been shown in hepatopathy caused by hepatotoxic drugs.

Appointment to patients with opioid addiction, accompanied by liver damage, leads to a regression of the clinical manifestations of withdrawal, an improvement in the functional state of the liver and microsomal oxidation processes.

Antidepressant activity appears gradually, starting from the end of the first week of treatment, and stabilizes within 2 weeks of treatment. The drug is effective in recurrent endogenous and neurotic depression resistant to amitriptyline. It has the ability to interrupt relapses of depression.

The purpose of the drug in osteoarthritis reduces the severity of pain, increases the synthesis of proteoglycans and leads to partial regeneration of cartilage tissue.

Pharmacokinetics

The tablets are film-coated, which dissolves only in the intestine, due to which ademetionine is released in the duodenum.

Suction

The bioavailability of the drug when taken orally is 5%, increases when taken on an empty stomach. C max ademetionine in plasma are dose-dependent and amount to 0.5-1 ml / l 3-5 hours after a single oral dose of 400 to 1000 mg. Cmax of ademetionine in plasma decreases to baseline within 24 hours.

Distribution

Plasma protein binding is negligible, ≤ 5%. Penetrates through the BBB. There is a significant increase in the concentration of ademetionine in the cerebrospinal fluid.

Metabolism

Biotransformed in the liver. The process of formation, consumption and re-formation of ademetionine is called the ademetionine cycle. In the first step of this cycle, ademethionine-dependent methylases use ademethionine 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 a reverse transformation to methionine by transferring a methyl group from 5-methyltetrahydrofolate. As a result, methionine can be converted to ademetionine, completing the cycle.

breeding

T 1/2 - 1.5 hours Excreted by the kidneys. In studies in healthy volunteers, oral administration of labeled (methyl 14 C) S-adenosyl-L-methionine in the urine revealed 15.5 ± 1.5% radioactivity after 48 hours, and in feces - 23.5 ± 3.5% radioactivity after 72 hours. Thus, about 60% was deposited.

Release form

Tablets, enteric-coated, film-coated, from white to white with a yellowish tint, oval, biconvex.

Excipients: colloidal silicon dioxide - 4.4 mg, microcrystalline cellulose - 93.6 mg, sodium carboxymethyl starch (type A) - 17.6 mg, magnesium stearate - 4.4 mg.

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

10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.

Dosage

The drug is prescribed inside. Tablets should be swallowed whole without chewing, it is advisable to take them in the morning between meals.

Tablets of the drug Heptral ® should be removed from the blister immediately before ingestion. If the tablets have a color other than white to white with a yellowish tint (due to leakage of aluminum foil), the use of Heptral® is not recommended.

Intrahepatic cholestasis

Depression

The dose ranges from 800 mg/day to 1600 mg/day.

The duration of therapy is determined by the doctor.

Elderly patients

Clinical experience with the use of the drug Heptral ® did not reveal any differences in its effectiveness in elderly patients and younger patients. However, given the high probability of existing violations of the liver, kidneys or heart, other comorbidities or concomitant therapy with other drugs, the dose of Heptral® in elderly patients should be selected with caution, starting the use of the drug from the lower end of the dose range.

Patients with kidney failure

Studies in patients with renal insufficiency have not been conducted, therefore, it is recommended to be careful when using the drug Heptral ® in such patients.

Patients with liver failure

Overdose

An overdose of the drug Heptral ® is unlikely. In case of overdose, it is recommended to monitor the patient and conduct symptomatic therapy.

Interaction

No known drug interaction of the drug Heptral ® with other drugs was observed.

There is a report of excess serotonin syndrome in a patient taking ademetionine and clomipramine. It is believed that such an interaction is possible and caution should be given to ademetionine together with selective serotonin reuptake inhibitors, tricyclic antidepressants (such as clomipramine), as well as herbal remedies and preparations containing tryptophan.

Side effects

Among the most frequent adverse reactions noted: nausea, abdominal pain and diarrhea. The following is a summary of the adverse reactions that were identified during clinical research and in post-marketing use of ademetionine both in tablets and injectable dosage form.

From the side immune system: hypersensitivity reactions, anaphylactoid or anaphylactic reactions (including hyperemia skin, shortness of breath, bronchospasm, back pain, discomfort in the area chest, decreased blood pressure, increased blood pressure, tachycardia, bradycardia).

From the side respiratory system: swelling of the larynx.

On the part of the skin: reactions at the injection site (very rarely with skin necrosis), Quincke's edema, increased sweating, skin reactions, skin-allergic reactions (including rash, pruritus, urticaria, erythema).

Infections and infestations: urinary tract infections.

From the side nervous system: dizziness, headache, paresthesia, anxiety, confusion, insomnia.

From the side of cardio-vascular system: "hot flashes", phlebitis of superficial veins, cardiovascular disorders.

From the digestive system: bloating, abdominal pain, diarrhea, dry mouth, dyspepsia, esophagitis, flatulence, gastrointestinal disorders, gastrointestinal bleeding, nausea, vomiting, hepatic colic, liver cirrhosis.

From the musculoskeletal system: arthralgia, muscle spasms.

Other: asthenia, chills, flu-like syndrome, malaise, peripheral edema, fever.

Indications

Intrahepatic cholestasis in precirrhotic and cirrhotic conditions, which can be observed in the following diseases:

• fatty degeneration of the liver;
• 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;
• cirrhosis of the liver;
• encephalopathy, incl. associated with liver failure (including alcohol).

Intrahepatic cholestasis in pregnant women.

Symptoms of depression.

Contraindications

• genetic disorders affecting the methionine cycle and / or causing homocystinuria and / or hyperhomocysteinemia (deficiency of cystathionine beta synthase, impaired metabolism of vitamin B 12);
• age up to 18 years (experience with medical use in children is limited);
• hypersensitivity to the components of the drug.

With caution, the drug should be prescribed for bipolar disorders; in the first trimester of pregnancy and during breastfeeding (use is possible only if the potential benefit to the mother outweighs the possible risk to the fetus and child); simultaneously with selective serotonin reuptake inhibitors (SSRIs); tricyclic antidepressants (such as clomipramine); herbal preparations and preparations containing tryptophan; elderly patients with renal insufficiency.

Application features

Use during pregnancy and lactation

The use of ademetionine in high doses in the third trimester of pregnancy did not cause any undesirable effects.

The use of the drug Heptral ® in the first trimester of pregnancy and during breastfeeding is possible only if the potential benefit to the mother outweighs the possible risk to the fetus or child.

Application for violations of liver function

The pharmacokinetic parameters of ademetionine are similar in healthy volunteers and in patients with chronic diseases liver.

Application for violations of kidney function

Use in children

special instructions

Given the tonic effect of the drug, it is not recommended to use it at bedtime.

When using the drug Heptral ® in patients with cirrhosis of the liver on the background of hyperazotemia, systematic monitoring of the nitrogen content in the blood is necessary. During long-term therapy, it is necessary to determine the content of urea and creatinine in the blood serum.

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

There are also reports of a sudden onset or increase in anxiety in patients taking ademetionine. In most cases, discontinuation of therapy is not required; in a few cases, the state of anxiety disappeared after a dose reduction or discontinuation of the drug.

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 blood plasma should be monitored. If deficiency is found, cyanocobalamin and folic acid are recommended before treatment with ademetionine or a one-day intake with ademethionine.

In immunological analysis, the use of ademetionine can contribute to a false determination of the high content of homocysteine ​​in the blood. For patients taking ademetionine, it is recommended to use non-immunological methods of analysis to determine the content of homocysteine.

Influence on the ability to drive a car and work with mechanisms

Some patients may experience dizziness while taking the drug Heptral ®. It is not recommended to drive a car and work with mechanisms while taking the drug until the patient is sure that the therapy does not affect the ability to engage in this kind of activity.