Hepa-Merz (Granules, Concentrate) Instructions for Use

ATC Code

A05BA (Drugs for the treatment of liver diseases)

Active Substance

Ornithine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Drug for the treatment of liver diseases

Pharmacotherapeutic Group

Drugs for the treatment of liver diseases

Pharmacological Action

Under in vivo conditions, L-Ornithine-L-aspartate exerts its effect through the amino acids ornithine and aspartate, which are involved in two key processes of ammonia detoxification: urea synthesis and glutamine synthesis.

Urea synthesis takes place in periportal hepatocytes. In these cells, ornithine acts both as an activator of the enzymes ornithine carbamoyltransferase and carbamoyl phosphate synthetase and as a substrate for urea synthesis. Glutamine synthesis takes place in perivenous hepatocytes. Aspartate and other dicarboxylates, including metabolic products of ornithine, are taken up by the cells and used to bind ammonia to form glutamine, especially under pathological conditions. Glutamate is an amino acid that binds ammonia under both physiological and pathophysiological conditions.

The resulting amino acid glutamine is not only a non-toxic form of ammonia excretion but also activates an important urea formation cycle (glutamine exchange).

Under physiological conditions, the role of ornithine and aspartate is not limited to participation in urea synthesis. Animal studies have shown that the ability of L-ornithine-L-aspartate to reduce ammonia levels is due to increased glutamine synthesis. Clinical studies have demonstrated an improvement in the branched-chain amino acids/aromatic amino acids ratio.

Furthermore, L-Ornithine-L-aspartate promotes the production of insulin and somatotropic hormone. It improves protein metabolism in diseases requiring parenteral nutrition. It helps reduce asthenic, dyspeptic, and pain syndromes, as well as normalize increased body weight (in steatosis and steatohepatitis).

Pharmacokinetics

L-Ornithine-L-aspartate is rapidly absorbed and broken down into ornithine and aspartate. Both amino acids have a short T_1/2 of 0.3-0.4 hours. A fraction of aspartate is excreted in the urine in an unmetabolized form.

Indications

• Acute and chronic liver diseases accompanied by hyperammonemia;
• Hepatic encephalopathy (latent or manifest);
• Steatosis and steatohepatitis (of various origins).

ICD codes

Dosage Regimen

Granules

The drug is taken orally.

The contents of 1-2 sachets are dissolved in a sufficient volume of liquid (e.g., a glass of water, tea, or juice) and taken during or after meals up to 3 times/day. The course of administration depends on the severity of the disease.

The ready-to-use solution should be consumed immediately after preparation.

Children

Experience with the use of the drug in children is limited.

Concentrate

Administer IV up to 4 ampoules/day, dissolving the contents of the ampoules in 500 ml of infusion solution.

In cases of early clouding of consciousness (pre-coma) or clouding of consciousness (coma), depending on the severity of the condition, administer up to 8 ampoules/day.

Before use, the contents of the ampoule are added to the infusion solution, and the infusion is performed in this form.

The drug can be mixed with conventional infusion solutions. To date, no peculiarities regarding miscibility have been observed. However, the contents of the ampoule should be added to the infusion solution only immediately before use. To ensure venous tolerance, no more than 6 ampoules should be dissolved in 500 ml of infusion solution.

The duration of infusion, frequency, and duration of treatment are determined individually.

The maximum rate of IV administration is 5 g (1 ampoule) per hour.

The drug must not be administered into an artery.

Children

Experience with the use of the drug in children is limited.

Adverse Reactions

Adverse reactions are classified by frequency of occurrence

From the digestive system uncommon – nausea, vomiting, abdominal pain, flatulence, diarrhea.

From the musculoskeletal system and connective tissue very rare – pain in the extremities.

The listed side effects are usually short-lived and do not require discontinuation of the drug.

The dye sunset yellow may cause allergic reactions.

Contraindications

• Hypersensitivity to L-ornithine-L-aspartate or to any of the excipients;
• Severe renal impairment, for which a serum creatinine level greater than 3 mg/100 ml may be used as a marker.

With caution during pregnancy.

Use in Pregnancy and Lactation

Pregnancy

There are no clinical data on the use of the drug during pregnancy. Comprehensive animal reproduction toxicity studies have not been conducted with L-ornithine-L-aspartate. Therefore, the drug should not be used during pregnancy. However, if therapy with the drug is considered necessary, a thorough benefit-risk assessment should be performed.

Breastfeeding period

There are no data on the ability of L-ornithine-L-aspartate to pass into breast milk. Therefore, the drug should not be used during breastfeeding. However, if therapy with the drug is considered necessary, a thorough benefit-risk assessment should be performed.

Fertility

There are no data on the effect of the drug on fertility.

Use in Hepatic Impairment

The drug is used according to the indications.

Use in Renal Impairment

The drug is contraindicated in severe renal failure (serum creatinine level >3 mg/100 ml).

Pediatric Use

Experience with the use of the drug in children is limited.

Special Precautions

The drug contains fructose. Patients with rare hereditary fructose intolerance should not take this drug. The drug contains 1.13 g of fructose in one sachet (equivalent to 0.11 XE). This should be taken into account by patients suffering from diabetes mellitus. The drug may have an adverse effect on the teeth (caries) with long-term use.

Children

Currently, there are no data on the use of the drug in children.

Effect on ability to drive vehicles and operate machinery

Due to hepatic encephalopathy, the ability to drive vehicles and operate machinery may be impaired even during treatment with L-ornithine-L-aspartate.

Overdose

Symptoms to date, no signs of intoxication due to overdose of L-ornithine-L-aspartate have been identified.

Treatment symptomatic therapy.

Drug Interactions

Drug interaction studies have not been conducted. To date, no interactions have been described.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years.

Dispensing Status

The drug is available without a prescription.

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.