Heptral-pharmex

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT HEPTROR-PHARMEKS

Composition:

Active substance: L-ornithine-L-aspartate;

One sachet contains 3 g of L-ornithine-L-aspartate;

Excipients: fructose, anhydrous citric acid, povidone K25, sodium saccharin (E 954), sodium cyclamate (E 952), orange flavor, lemon flavor, Sunset Yellow coloring (E 110).

Pharmaceutical form. Granules.

Main physicochemical characteristics: granules ranging from white-orange to orange in color, with a citrus odor.

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 mediated by the amino acids ornithine and aspartate and occurs through two key mechanisms of ammonia detoxification: urea synthesis and glutamine synthesis.

Urea synthesis takes place in periportal hepatocytes, where ornithine acts as an activator of two enzymes: ornithine carbamoyltransferase 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 to bind ammonia in the form of glutamine.

Glutamate is the amino acid that binds ammonia under both physiological and pathological conditions. The resulting amino acid, glutamine, represents not only a non-toxic form for ammonia elimination but also stimulates 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 individual clinical studies, this improvement has been demonstrated regarding the ratio of branched-chain amino acids to aromatic amino acids.

L-ornithine-L-aspartate is rapidly absorbed and metabolized into ornithine and aspartate.

Pharmacokinetics.

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

Clinical characteristics.

Indications.

Treatment of concomitant diseases and complications caused by impaired hepatic detoxification function (e.g., in liver cirrhosis) associated with symptoms of latent or overt hepatic encephalopathy.

Contraindications.

Hypersensitivity to L-ornithine-L-aspartate, the colorant "Sunset Yellow" (E 110), or to any of the excipients of the medicinal product.

Severe renal impairment (renal failure) when creatinine levels exceed 3 mg/100 ml.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted. Data are lacking.

Special precautions for use

HEPTOR-PHARMEKS granules contain 1.135 g of fructose per sachet (equivalent to 0.11 carbohydrate exchange units), which should be taken into account for patients with diabetes mellitus.

Do not use in patients with hereditary fructose intolerance.

Prolonged use of the drug may be harmful to teeth (development of dental caries).

The colouring agent Sunset Yellow (E 110) may cause allergic reactions.

Prolonged use of high doses of the drug may increase plasma uric acid levels; therefore, monitoring of plasma and urinary urea levels is necessary. Do not use in patients with phenylketonuria.

Use during pregnancy or breastfeeding

There are no data available on the use of HEPTOR-PHARMEKS granules during pregnancy. Animal studies with L-ornithine-L-aspartate to evaluate its toxic effects on reproductive function have not been conducted. Therefore, use of HEPTOR-PHARMEKS granules during pregnancy should be avoided.

However, if administration of the medicinal product during pregnancy is considered necessary due to life-threatening indications, the physician should carefully weigh the potential risk to the fetus (child) against the expected benefit to the mother.

It is unknown whether L-ornithine-L-aspartate passes into breast milk. Therefore, use of HEPTOR-PHARMEKS should be avoided during breastfeeding.

Ability to influence reaction rate while driving or operating machinery

Due to the underlying disease, the ability to drive or operate machinery may be impaired during treatment with L-ornithine-L-aspartate; therefore, such activities should be avoided during treatment.

Administration and Dosage.

Dissolve the contents of 1–2 packets of HEPTRAL-PHARMEKS in a large amount of liquid (for example, in a glass of water or juice) and take during or after meals. Administer up to 3 times daily.

The duration of treatment is determined by the physician depending on the patient's clinical condition.

Children.

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

Overdose.

In case of overdose, an increase in blood urea and urea in urine may be observed, along with intensification of adverse reactions.

Signs of intoxication caused by overdose of L-ornithine-L-aspartate have not been observed to date.

Treatment. No specific antidote is known. Gastric lavage and symptomatic treatment are recommended.

Side effects.

The frequency of adverse reactions is specified as follows:

very common (≥ 1/10);

common (≥ 1/100, < 1/10);

uncommon (≥ 1/1000, < 1/100);

rare (≥ 1/10000, < 1/1000);

very rare (< 1/10000);

frequency not known: cannot be estimated based on available data.

Gastrointestinal disorders:

uncommon: nausea, vomiting, stomach pain, flatulence, diarrhea, constipation.

Musculoskeletal system disorders:

very rare: joint pain, muscle pain.

Skin and subcutaneous tissue disorders: skin rash, redness of the skin, itching, urticaria.

Neurological disorders: dizziness.

Immune system disorders: hypersensitivity reactions, including angioneurotic edema, anaphylactic shock, sneezing, lacrimation.

Metabolic and nutritional disorders: with high-dose administration, increased plasma uric acid levels are possible.

These adverse reactions are usually transient and do not require discontinuation of the drug.

The dye "Sunset Yellow" (E 110) may cause allergic reactions.

Reporting of adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Do not use after the expiry date stated on the packaging.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging. 5 g of granules in a sachet, 30 sachets in a cardboard box.

Availability. Over-the-counter.

Manufacturer.

PHARMEKS GROUP LLC.

LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Manufacturer's address and place of business.

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

(PHARMEKS GROUP LLC)

22, Shevchenka Street, Kharkiv, Kharkiv region, 61013, Ukraine.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")