Hepadif

Pharmacological properties

Hepadif is a combined drug whose pharmacological effects are due to the complex action of its components. It stimulates the metabolism of fats - components of the β-oxidative conversion of free fatty acids in hepatocyte mitochondria, biosynthetic processes, prevents hepatocyte necrosis, normalizes hepatocyte proliferation processes, the system of liver enzymes and helps restore normal liver function. the presence of adenosine, which is a component of coenzymes, nucleic acids, ensures the regulation of hematopoiesis. B vitamins (cyanocobalamin, riboflavin, pyridoxine) regulate redox processes in the body, participate in protein, fat and carbohydrate metabolism, in the exchange of amino acids - tryptophan, methionine, cysteine, glutamic acid and other amino acids. pyridoxine contributes to the normalization of lipid metabolism, the functioning of the central and peripheral nervous system. cyanocobalamin is involved in the process of transmethylation, hydrogen transfer, synthesis of methionine, nucleic acids, choline, creatine, helps to normalize impaired functions of the liver, nervous system, blood formation, increases the ability of tissues to regenerate. cyanocobalamin and pyridoxine reduce fatty liver, reduce hyperhomocysteinemia. riboflavin is part of the enzymes involved in the transport of oxygen and the formation of atph in mitochondria.

Carnitine regulates the metabolism of fats, promotes the breakdown of long chain fatty acids and the replacement of a fatty acid metabolic shunt with a carbohydrate, reduces the indicators of fatty degeneration of the liver, and improves the absorption of food.

The antitoxic fraction of the liver extract is an indispensable and interchangeable amino acids that participate in the synthesis of proteins, are donors of sulfhydryl and methyl groups, have antitoxic and antioxidant effects.

Hepadif stimulates the digestion and secretion of bile, facilitates the absorption of carbohydrates in the small intestine, is necessary for the functioning of the normal intestinal microflora. Helps increase the glycogen-fixing, synthetic, antitoxic function of the liver, increases the sensitivity of cells to insulin, and promotes the increase of insulin.

Pharmacokinetics Capsules After oral administration, a complex of active substances is released in the duodenum. The absorption of water-soluble B vitamins (cyanocobalamin, riboflavin, pyridoxine), carnitine orotate, the antitoxic fraction of the liver extract, adenine hydrochloride occurs along the entire length of the small intestine. Cyanocobalamin is deposited mainly in the liver, as well as in the kidneys, intestinal wall. Re-absorbed in the lumen of the intestine, where it is excreted along with bile. Riboflavin is distributed unevenly in the body: the largest amount is detected in the myocardium, liver, and kidneys. Pyridoxine is metabolized in the liver with the formation of pharmacologically active metabolites (pyridoxalphosphate, pyridoxaminophosphate); distributed in muscles, liver, central nervous system. Excretion is carried out mainly by the kidneys.

Rr. After iv drip, the distribution of the active components of the drug - water-soluble B vitamins (cyanocobalamin, pyridoxine), carnitine, the antitoxic fraction of the liver extract, adenosine - occurs mainly in the liver and kidneys. Pyridoxine is metabolized in the liver with the formation of pharmacologically active metabolites (pyridoxalphosphate, pyridoxaminophosphate), distributed in the muscles, liver, and central nervous system. It is allocated mainly by kidneys.

Indications

As part of complex therapy: acute and chronic hepatitis, cirrhosis; fatty liver (liver steatosis); alcoholic liver damage; intoxication due to prolonged use of antitumor and anti-tuberculosis drugs.

Application

Hepadif capsules. taken orally. adult patients - 2 capsules 2-3 times a day, regardless of food intake.

Usually, capsules are taken whole, washed down with water. If swallowing is difficult, the contents of the capsule can be dissolved in 50 ml of juice or water. Do not dissolve in milk!

The dosage can be adjusted by the doctor.

Elderly people do not need dose adjustment.

The duration of treatment depends on the course of the underlying disease and is determined in each case individually.

Dr. Hepadif. Apply iv drip 1 time per day. The average daily dose for adults is 8.625 mg / kg body weight, which corresponds to the contents of 1 bottle of the drug, dissolved in 400-500 ml of 5% glucose solution. The maximum daily dose is 17.25 mg / kg body weight, which corresponds to the contents of 2 vials of the drug, dissolved in 400-500 ml of 5% glucose solution.

Elderly people do not need dose adjustment.

Children aged 7-14 years: the daily dose of the drug is similar to that for adult patients. The dosage may be adjusted by the doctor.

The duration of treatment depends on the course of the underlying disease and is determined in each case individually.

Contraindications

Individual hypersensitivity to the components of the drug. nephrolithiasis, erythremia, erythrocytosis, thromboembolism, peptic ulcer of the stomach and duodenum in the acute stage.

Side effects

Usually the drug is well tolerated.

On the part of the blood: hypercoagulation.

From the cardiovascular system: tachycardia, pain in the heart.

From the nervous system: headache, dizziness, nervous excitement, drowsiness, impaired coordination, paresthesia, numbness in the extremities, the appearance of symptoms of “stocking” and “gloves”, loss of consciousness and the development of seizures with rapid administration.

From the respiratory system: shortness of breath.

From the side of metabolism: acne, bullous rash, nausea, sweating, impaired purine metabolism, decreased folic acid level.

On the part of the immune system: hypersensitivity reactions, including skin manifestations (hyperemia, urticaria, rash, itching, dermatitis, photosensitivity, etc.), edema (Quinckes edema), respiratory failure (suffocation, anaphylactic shock, angioedema, anaphylactoid reactions).

From the gastrointestinal tract: dyspepsia, pain and discomfort in the abdomen, pain in the epigastric region, heartburn, increased gastric secretion, nausea, vomiting, diarrhea, constipation, weakening of the stool.

From the reproductive system and mammary glands: suppression of lactation in the lactogenic period.

Common disorders: malaise, weakness, fever.

Local reactions: changes at the injection site, including flushing, burning, itching, pain, swelling, induration and necrosis at the injection site.

The presence of methyl parahydroxybenzoate (E219), propyl parahydroxybenzoate (E217) in the preparation can cause allergic reactions (possibly delayed), and in some cases bronchospasm.

special instructions

Use with caution in patients with a history of gastric and duodenal ulcers (due to a possible increase in the acidity of gastric juice), in severe diseases of the heart and kidneys, and neoplasms.

The use of the drug can lead to a false positive test for urobilinogen using Ehrlich reagent.

Parenteral Administration of Vitamin B₁₂ may temporarily affect the diagnosis of funicular myelosis or pernicious anemia. It can not be used with drugs that increase blood coagulation.

For people with a tendency to thrombosis and patients with angina pectoris during treatment, care must be taken to monitor blood coagulation.

During treatment should not drink alcoholic beverages.

Use during pregnancy and lactation. There is no data on the negative effect of the drug in the indicated period, however, when prescribing Hepadif during pregnancy or breastfeeding, it is necessary to take into account the ratio of possible benefits for the mother and potential risk to the fetus / child.

Children. Due to the lack of clinical experience with the use of Hepadif, it can be prescribed to children over the age of 7 years.

Influence on the ability to drive vehicles and work with mechanisms. There was no negative impact on the ability to drive vehicles and work with mechanisms.

Interactions

Vitamin B6 weakens the effect of levodopa, prevents or reduces the severity of toxic manifestations that are noted with the use of isoniazid and other anti-TB drugs.

PASK, cimetidine, calcium preparations, ethanol reduce the absorption of vitamin B₁₂.

Riboflavin is incompatible with streptomycin and reduces the effectiveness of antibacterial drugs (oxytetracycline, doxycycline, erythromycin, tetracycline and lincomycin). Tricyclic antidepressants, imipramine and amitriptyline, inhibit the metabolism of riboflavin, especially in the heart tissue.

Interactions due to the presence of cyanocobalamin

Aminoglycosides, salicylates, antiepileptic drugs, colchicine, potassium preparations reduce the absorption of the drug, affect its kinetics.

With simultaneous use with kanamycin, neomycin, polymyxins, tetracyclines, the absorption of cyanocobalamin is reduced.

It is pharmaceutically incompatible with ascorbic acid, salts of heavy metals (inactivation of cyanocobalamin), thiamine bromide, pyridoxine, riboflavin (the cobalt ion contained in the molecule of cyanocobalamin destroys other vitamins).

Thiamine increases the risk of allergic reactions caused by thiamine.

Chloramphenicol reduces the hematopoietic response to the drug.

With simultaneous use, the effect of the combination of acetylsalicylic acid, caffeine, paracetamol is reduced.

Oral contraceptives reduce the concentration of cyanocobalamin in the blood.

Interactions due to the presence of pyridoxine hydrochloride

Diuretics: when combined with pyridoxine, the effect of diuretics is enhanced.

Hormonal contraceptives, cycloserine, penicillamine, isoniazid, dihydralazine sulfate, ethionamide, immunosuppressants - when combined with pyridoxine, the effect of the latter is weakened.

Sleeping pills and sedatives: when combined with pyridoxine, sleeping pills are reduced.

Anti-Parkinsonian drugs: when combined with pyridoxine, the effectiveness of drugs for the treatment of patients with Parkinsons disease decreases.

Phenytoin: when combined with pyridoxine, the effect of phenytoin is weakened.

GCS: when combined with pyridoxine, the amount of vitamin B decreases₆ in organism.

Glutamic acid, a combination of magnesium and potassium aspartate: when combined with pyridoxine, increased resistance to hypoxia.

Cardiac glycosides: when combined with pyridoxine, the synthesis of contractile proteins in the myocardium increases.

Tricyclic antidepressants: when combined with pyridoxine, the latter eliminates the side effects of tricyclic antidepressants associated with their anticholinergic activity (dry mouth, urinary retention).

Resorptive chloramphenicol preparations: when combined with pyridoxine, the latter prevents ophthalmic complications arising from prolonged use of resorptive chloramphenicol preparations (chloramphenicol).

Overdose

Symptoms: nausea, vomiting, diarrhea, increased severity of adverse reactions. with prolonged use in high doses, peripheral neuropathy is possible.

Pyridoxine hydrochloride. During prolonged use of vitamin B₆ (6–12 months) at a dose of 50 mg daily or at a dose of 1 g / day (2 months) reversible peripheral sensory neuropathy is possible. In the event of symptoms of peripheral sensory neuropathy (paresthesia), the dose of the drug must be corrected and treatment should be stopped if necessary.

Neuropathy with ataxia and sensitivity disorders, cerebral seizures with changes in the EEG, as well as in some cases hypochromic anemia and seborrheic dermatitis are described after administration of the drug at a dose of 2 g / day.

Cyanocobalamin. After parenteral administration (in rare cases, after oral administration) of the drug in doses higher than recommended, allergic reactions, eczematous skin disorders and a benign form of acne were noted.

With prolonged use in high doses, a violation of the activity of liver enzymes, pain in the heart, hypercoagulation is possible.

Treatment: gastric lavage, activated charcoal, hyperosmolar laxatives.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° C.