Heptral-pharmex

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT HEPTOR-PHARMEX (HEPTOR-PHARMEX)

Composition:

Active substance: L-ornithine-L-aspartate;

1 ml of concentrate contains L-ornithine-L-aspartate 500 mg (calculated as 100 % anhydrous substance);

Excipient: water for injections.

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical properties: clear colorless or slightly yellow solution.

Pharmacotherapeutic group.

Drugs used in liver diseases, lipotropic agents. Hepatotropic agents. ATC code A05BA.

Pharmacological Properties

Pharmacodynamics

In vivo, the action of L-ornithine-L-aspartate is due to the amino acids ornithine and aspartate and consists of detoxification of ammonia through the synthesis of urea and glutamine.

Urea synthesis occurs in periportal hepatocytes, where ornithine acts as an activator of two enzymes: ornithine carbamoyl transferase and carbamoyl phosphate synthetase, as well as a substrate for urea synthesis.

Glutamine synthesis occurs in perivenous hepatocytes. In particular, under pathological conditions, aspartate and dicarboxylates, including metabolites of ornithine, are taken up by cells and used there for binding ammonia into glutamine.

Glutamate is the amino acid that binds ammonia under both physiological and pathophysiological conditions. The resulting amino acid, glutamine, is not only a non-toxic form for ammonia elimination, but also activates the important urea cycle (intracellular glutamine metabolism).

Under physiological conditions, ornithine and aspartate do not limit urea synthesis.

Animal experimental studies have shown that the ability of L-ornithine-L-aspartate to reduce ammonia levels is due to accelerated glutamine synthesis. In some clinical studies, this improvement has been demonstrated with respect to branched-chain amino acids/aromatic amino acids.

Pharmacokinetics

The elimination half-life of both ornithine and aspartate is short—0.3–0.4 hours. A small portion of aspartate is excreted unchanged in urine.

Clinical characteristics.

Indications.

Symptomatic treatment of latent and overt hepatic encephalopathy.

Contraindications.

Hypersensitivity to L-ornithine-L-aspartate or to any of the excipients.

Severe renal impairment (renal failure) with creatinine levels above 3 mg/100 ml (considered as an approximate threshold).

Interaction with other medicinal products and other forms of interaction.

No interaction studies have been conducted. No interactions are currently known.

Special precautions for use

The medicinal product Heptral-Farmeks, concentrate for solution for infusion, must not be administered intra-arterially.

When high doses of Heptral-Farmeks are administered, plasma and urine urea levels should be monitored.

In patients with impaired liver function, the infusion rate should be adjusted according to the individual patient's condition in order to prevent nausea and vomiting.

Use during pregnancy or breastfeeding

Data on the use of L-ornithine-L-aspartate during pregnancy are lacking. Studies in animals to evaluate the toxic effects of L-ornithine-L-aspartate on reproductive function have not been conducted. Therefore, the use of L-ornithine-L-aspartate during pregnancy should be avoided.

However, if treatment with L-ornithine-L-aspartate during pregnancy is considered necessary based on life-threatening indications, the physician should carefully weigh the potential risk to the fetus/child against the expected benefit to the woman.

It is unknown whether L-ornithine-L-aspartate is excreted in human breast milk. Therefore, the use of L-ornithine-L-aspartate should be avoided during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

The ability to drive or operate machinery may be impaired during treatment with the medicinal product Heptral-Farmeks; therefore, such activities should be avoided during therapy.

Method of administration and dosage.

Administer intravenously.

The usual dose is up to 4 vials (40 ml) per day.

In cases of precoma or coma, administer up to 8 vials (80 ml) within 24 hours, depending on the severity of the condition.

Heptral-Farmeks concentrate for infusion solution may be mixed with standard infusion solutions.

The contents of the vial with Heptral-Farmeks concentrate should be mixed with infusion solution only immediately before use. Before administration, add the contents of the vials to 500 ml of infusion solution; however, do not dissolve more than 6 vials in 500 ml of infusion solution.

The maximum infusion rate is 5 g/hour (corresponding to the contents of 1 vial).

The duration of treatment is determined by the physician according to the patient's clinical condition.

Children. Experience with use in children is limited; therefore, the drug should not be used in pediatric practice.

Overdose.

To date, there have been no reported signs of intoxication due to overdose of L-ornithine-L-aspartate. However, adverse effects may be intensified. In case of overdose, symptomatic treatment is recommended.

Side effects.

The adverse reactions listed below are classified by system organ class and frequency of occurrence. The following frequency classification is used: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from available data).

Immune system disorders

Not known: hypersensitivity, anaphylactic reactions.

Gastrointestinal disorders

Uncommon: nausea.

Rare: vomiting.

Gastrointestinal symptoms are generally transient and do not require discontinuation of treatment. They resolve with dose reduction or slower administration rate.

Shelf life. 3 years.

Storage conditions.

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

Keep out of the reach of children.

Incompatibility.

Since compatibility studies have not been conducted, this medicinal product must not be mixed with other medicinal products.

Geptror-Farmeks can be mixed with standard infusion solutions. However, no more than 6 vials should be dissolved in 500 ml of infusion solution.

Packaging.

10 ml in a vial. 5 vials in a blister pack. 1 or 2 blister packs in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

LLC "FARMEKS GROUP".

Manufacturer's address and location of operations.

100, Shevchenka Street, Boryspil, Kyiv Oblast, 08301, Ukraine.