Larnamin®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LARNAMIN® (LARNAMIN)

Composition:

Active substance: L-ornithine-L-aspartate;

1 ml of the preparation contains 500 mg of L-ornithine-L-aspartate calculated as 100 % substance;

Excipient: water for injections.

Pharmaceutical form. Concentrate for solution for infusion.

Main physicochemical properties: clear solution, colorless to slightly yellow.

Pharmacotherapeutic group.

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

Pharmacological Properties

Pharmacodynamics

The in vivo action of L-ornithine-L-aspartate is mediated by the amino acids ornithine and aspartate through two key mechanisms of ammonia detoxification: urea synthesis and glutamine synthesis.

Urea synthesis occurs 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 utilized there for ammonia binding in the form of glutamine.

Glutamate is an amino acid that binds ammonia under both physiological and pathological 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 individual clinical studies, this improvement has been demonstrated regarding the ratio of branched-chain amino acids to 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.

Treatment of concomitant diseases and complications caused by impaired hepatic detoxification function (e.g., in liver cirrhosis) associated with symptoms of latent or manifest hepatic encephalopathy, particularly disturbances of consciousness (precoma, coma).

Contraindications.

Hypersensitivity to L-ornithine-L-aspartate or to any of the other components of the medicinal product.

Severe renal insufficiency (serum creatinine level above 3 mg/100 ml is considered an approximate threshold).

Interaction with other medicinal products and other forms of interaction.

No interaction studies have been conducted. Interactions are currently unknown.

Special precautions for use.

Larnamin®, concentrate for solution for infusion, must not be administered intra-arterially.

When high doses of Larnamin® are administered, plasma and urinary urea levels should be monitored.

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

Use during pregnancy or breastfeeding.

There are no data available on the use of Larnamin® during pregnancy. Animal studies to evaluate the reproductive toxicity of Larnamin® have not been conducted. Therefore, the use of Larnamin® during pregnancy should be avoided.

However, if treatment with Larnamin® during pregnancy is considered necessary based on life-threatening indications, the physician should carefully weigh the potential risk to the fetus/infant against the expected benefit to the mother.

It is unknown whether Larnamin® is excreted in human breast milk; therefore, use of the drug should be avoided during breastfeeding.

Ability to affect 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 Larnamin®; therefore, such activities should be avoided during therapy.

Dosage and Administration

Administer intravenously.

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

In cases of precoma or coma, up to 8 ampoules (80 ml) may be administered within 24 hours, depending on the severity of the condition.

Before administration, the contents of the ampoules should be added to 500 ml of infusion solution; however, no more than 6 ampoules should be dissolved in 500 ml of infusion solution.

The maximum infusion rate of Larnamin® is 5 g/hour (equivalent to the contents of 1 ampoule).

The duration of treatment should be 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.

Signs of intoxication due to Larnamin® overdose have not been observed to date. Overdose may enhance adverse effects. In case of overdose, symptomatic treatment is recommended.

Side effects.

Gastrointestinal tract

Very rare (<1/10,000): nausea.

Rare (>1/10,000, <1/1,000): vomiting.

Generally, these symptoms are transient and do not require mandatory discontinuation of the drug. They resolve with dose reduction or slower administration rate.

Allergic reactions are possible.

Shelf life. 2 years.

Do not use the drug after the expiry date stated on the package.

Storage conditions.

Store at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility.

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

Larnamin® can be mixed with standard infusion solutions. However, no more than 6 ampoules should be dissolved in 500 ml of infusion solution.

Packaging.

10 ml in an ampoule.

5 or 10 ampoules per pack.

5 ampoules in a blister. 1 or 2 blisters per pack.

Prescription status.

Prescription only.

Manufacturer.

JSC "Farmak".

Manufacturer's name and address of the place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.