Hepasol-Neo (Solution) Instructions for Use

Marketing Authorization Holder

Hemofarm, A.D. (Serbia)

ATC Code

B05BA01 (Amino acids)

Dosage Form

Hepasol-Neo

Infusion solution 8%: fl. 500 ml 1 or 10 pcs. in a set with holders

Dosage Form, Packaging, and Composition

Infusion solution 8% transparent, from colorless to pale yellow.

Excipients : glacial acetic acid – 4.42 g/L, water for injections – up to 1 L.

500 ml – glass bottles (1) in a set with a plastic holder – cardboard packs.
500 ml – glass bottles (10) in a set with plastic holders (10 pcs.) – cardboard boxes

Clinical-Pharmacological Group

Agent for parenteral nutrition (amino acid solution), used for hepatic insufficiency

Pharmacotherapeutic Group

Parenteral nutrition agent, amino acid

Pharmacological Action

A combined preparation for parenteral nutrition. It has a hepatoprotective and detoxifying effect and participates in metabolic processes.

The preparation contains all 8 essential amino acids, 2 conditionally essential amino acids (L-arginine and L-histidine), which are synthesized in insufficient quantities in certain pathophysiological conditions, and 5 non-essential amino acids that provide adequate metabolism in patients with liver diseases. The amino acids are in the L-form, which allows for their direct participation in protein biosynthesis (nitrogen content – total 12.9 g/L).

L-arginine promotes the conversion of ammonia into urea and binds toxic ammonium ions formed during protein catabolism in the liver.

L-alanine and L-proline reduce the body’s need for glycine (this amino acid is poorly absorbed in the body, and its replacement makes the development of hyperammonemia impossible).

L-Isoleucine, L-leucine and L-valine (essential branched-chain amino acids) are directly absorbed by peripheral tissues (their metabolism does not depend on the degree of liver damage), reduce the absorption and entry of aromatic amino acids into the CNS, reducing the manifestations of hepatic encephalopathy, and normalize the energy and nitrogen balance in the body.

Hepasol-Neo allows for the correction of amino acid imbalances in hepatic insufficiency, as well as significantly improves protein tolerance in patients with liver cirrhosis and hepatitis and reduces the severity of symptoms of hepatic encephalopathy.

The preparation does not contain carbohydrates or electrolytes.

Pharmacokinetics

Amino acids administered by infusion follow one of two possible metabolic pathways: an anabolic pathway, in which amino acids are bound by peptide bonds and form specific proteins, and a catabolic pathway, in which amino acids undergo transamination.

When administered as part of total parenteral nutrition together with glucose and fats (carbohydrate to fat ratio 70:30) at a rate of 10.5 mg nitrogen/kg/h, amino acids reach a balanced concentration in the blood after 3 hours.

Amino acid metabolism occurs in all tissues of the body. The degree of their breakdown depends on the severity of the stress to which the body is subjected. Stress accelerates amino acid metabolism and enhances liver dysfunction, which in turn reduces amino acid metabolism. Sepsis also accelerates their metabolism, while decreased kidney function suppresses it.

Amino acids can be excreted unchanged with a rapid increase in their blood concentration. The T_1/2 of amino acids (in healthy people) is 5-15 minutes (during this short period, amino acids must be used for protein synthesis). The residues of amino acids not used in the protein synthesis process are subject to deamination, which produces urea excreted from the body. During the infusion of Hepasol-Neo, the absorption percentage of essential acids is 99%, and that of non-essential acids is 97%. At the same time, the total and renal clearance of essential amino acids is 0.5 L/min, i.e., 1.5 ml/min, and for most non-essential amino acids – 0.6 L/min, i.e., 3 ml/min. Arginine is almost completely reabsorbed in the renal tubules.

Indications

• Therapy and parenteral nutrition (partial or complete – with the addition of carbohydrate solutions and fat emulsions) for impaired liver function (hepatic insufficiency) with impaired brain function (hepatic encephalopathy) and without it;
• Therapy of hepatic coma and precomatous states.

ICD codes

Dosage Regimen

It is established individually, taking into account the blood ammonia concentration and the severity of the disease.

Hepasol-Neo is administered intravenously by drip at a rate of 1.0-1.25 ml/kg body weight/h (30-35 drops/min), which corresponds to 0.08-0.1 g of amino acids/kg/h. The maximum rate of administration is 1.25 ml/kg/h (respectively 0.1 g of amino acids/kg/h).

The maximum daily dose is 18.75 ml/kg body weight (1.5 g of amino acids/kg/day), i.e., 1300 ml for patients weighing 70 kg.

The duration of therapy is established individually until the complete disappearance of neurological symptoms.

Adverse Reactions

When used according to the indications in the recommended doses, side effects of this preparation are unknown.

Contraindications

• Disorders of amino acid metabolism;
• Hyperhydration;
• Hyponatremia;
• Hypokalemia;
• Renal failure (in hepatic coma in patients with renal failure, it is necessary to consider which of the two conditions threatens the patient’s life);
• Heart failure (in the stage of decompensation);
• Pregnancy;
• Lactation period;
• Children and adolescents under 18 years of age (efficacy and safety have not been established);
• Hypersensitivity to the components of the preparation.

Use in Pregnancy and Lactation

The efficacy and safety of Hepasol-Neo use during pregnancy and lactation have not been established. The use of the preparation in this category of patients is contraindicated.

Use in Hepatic Impairment

The preparation can be used according to the indications

Use in Renal Impairment

The preparation is contraindicated for use in renal failure (in hepatic coma in patients with renal failure, it is necessary to consider which of the two conditions threatens the patient’s life).

Pediatric Use

Contraindication: children and adolescents under 18 years of age (efficacy and safety have not been established).

Special Precautions

The use of Hepasol-Neo solution is advisable only for the listed indications.

During the use of this preparation, periodic monitoring of electrolyte and acid-base status, the degree of body hydration, and the state of kidney function is necessary.

Only a transparent solution from an undamaged bottle should be used!

Use in pediatrics

The efficacy and safety of Hepasol-Neo use in children and adolescents under 18 years of age have not been established.

Overdose

Symptoms nausea, vomiting, sweating, fever, tachycardia, increased activity of liver enzymes and concentration of residual nitrogen. An increased rate of administration can lead to hyperhydration and the appearance of peripheral edema, and the development of pulmonary edema.

Treatment : it is recommended to stop the infusion of the preparation and start symptomatic therapy. There is no specific antidote.

Drug Interactions

There are data on the in vivo interaction of Hepasol-Neo components with theophylline, leading to an increase in clearance.

Numerous data on in vitro interactions are known, so it is not recommended to add other medicinal products to the Hepasol-Neo solution.

Pharmaceutical interaction

Hepasol-Neo solution is compatible with antibiotics – amikacin, ampicillin, cefotaxime, ceftriaxone, doxycycline, erythromycin, gentamicin, chloramphenicol, clindamycin, netilmicin, penicillin, piperacillin, tetracycline, tobramycin and vancomycin, as well as with aminophylline, cyclophosphamide, cimetidine, cytarabine, digoxin, dopamine, famotidine, phytomenadione, fluorouracil, folic acid, furosemide, heparin, chlorpromazine, insulin, calcium gluconate, lidocaine, methyldopa, methylprednisolone, metoclopramide, methotrexate, morphine, nizatidine, norepinephrine, propranolol, ranitidine and riboflavin.

Storage Conditions

The preparation should be stored out of the reach of children, protected from light, at a temperature from 15°C (59°F) to 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Dispensing Status

The preparation is dispensed by prescription. The preparation should be used only in inpatient medical institutions.

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.