Lornit Infusion

L-Ornithine L -Aspartate Infusion Concentrate

Each ml contains:

L-Ornithine L-Aspartate 0.5 gm

Water for Injections IP q.s.

Concentrate for solution for infusion.

One ampoule of 10 ml contains 5 g L-Ornithine-L-Aspartate.

4.1 Therapeutic indications

• Latent and manifest hepatic encephalopathy.
• For pre coma & coma due to conditions (like cirrhosis) leading to impaired hepatic detoxification.

4.2 Posology and method of administration

The recommended dose is up to 4 ampoules (20 gram) per day. In case of pre-coma or coma up to 8 ampoules (40 gram) within 24 hours, depending on the severity of the condition.

The ampoules are added to an infusion solution before use, and infused in this form:

• Maximum Infusion Rate: 5 grams of L-ornithine L-aspartate (corresponding to the content of 1 ampoule) per hour.
• Maximum concentration: 6 ampoules per 500 ml of infusion solution.
• Infusion solutions: Normal saline, Dextrose, Ringer Lactate etc.

Lornit infusion concentrate must not be administered into an artery. Experience in children is limited.

4.3 Contraindications

• Hypersensitivity to L-ornithine L-aspartate.
• Severely impaired renal function (renal insufficiency- A serum creatinine > 3 mg/100 ml can be used as a guidance value.

4.4 Special warnings and precautions for use

At high doses of Lornit infusion concentrate, serum and urine urea levels should be monitored.

If liver function is substantially impaired, the infusion rate must be adjusted to the individual patient in order to prevent nausea and vomiting.

No data are so far available on the use of the drug in children.

4.5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed. Up to now interactions are not known.

4.6 Pregnancy and lactation

There are no clinical data available on the use of Lornit infusion concentrate in pregnancy.

L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies. The administration of Lornit infusion concentrate in pregnancy should therefore be avoided. If treatment with Lornit is nevertheless thought to be necessary, the benefits and risks should be carefully assessed.

It is not known whether L-ornithine L-aspartate passes into breast milk. Administration of Lornit should therefore be avoided during lactation. If treatment with Lornit is nevertheless thought to be necessary, the benefits and risks should be carefully assessed.

4.7 Effects on ability to drive and use machines

Depending on the underlying disease, the ability to drive and operate machines may also be impaired on treatment with L-ornithine L-aspartate.

4.8 Undesirable effects

Gastrointestinal disorders

Uncommon: Nausea

Rare: Vomiting

Generally, however, these symptoms are transient, and do not necessitate discontinuation of treatment with this medicinal product. They disappear on reduction of the dose or infusion rate.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to: medico@zuventus.com

Website: https://www.zuventus.com/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

So far signs of intoxication have not been observed following an overdose of L-ornithine L-aspartate. Cases of overdose require symptomatic treatment.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Liver therapy, ATC code: A05BA

In human body, L-ornithine L-aspartate acts on two key ammonia detoxification pathways – urea synthesis and glutamine synthesis – via the amino acids ornithine and aspartate. Urea synthesis takes place in the periportal hepatocytes, in which ornithine serves both as an activator of the two enzymes ornithine carbamoyl

transferase and carbamoyl phosphate synthetase and as a substrate for urea synthesis. Glutamine synthesis is localised in the perivenous hepatocytes. Under pathological conditions in particular, aspartate and other dicarboxylates – including metabolic products of ornithine – are taken up into the cells where they are used in the form of glutamine to bind ammonia.

Both physiologically and pathophysiologically glutamate serves as an ammonia-binding amino acid. The resulting amino acid glutamine not only provides a non-toxic form for the excretion of ammonia but also activates the important urea cycle (intercellular glutamine exchange).

Under physiological conditions ornithine and aspartate are not limiting for urea synthesis. Experimental studies in animal’s point to increased glutamine synthesis as a mechanism of the ammonia- lowering effect. Some clinical studies have shown an improvement in the ratio of branched chain to aromatic amino acids.

5.2 Pharmacokinetic properties

Ornithine and aspartate have a short elimination half-life of 0.3–0.4 hours. Some of the aspartate is excreted unchanged in the urine.

5.3 Preclinical safety data

Based on pharmacological safety studies, preclinical data show that with correct use there is no particular risk of toxicity following repeated administration or mutagenicity in humans. No studies on carcinogenic potential have been carried out. In a dose discovery study, L-ornithine L-aspartate was investigated for reproduction toxicity only to a limited extent.

None stated

L-Ornithine-L-Aspartate is a stable salt of the amino acids ornithine and aspartic acid. Reduces blood ammonia concentrations and improves mental function when administered IV in patients with hepatic encephalopathy.

Molecular Formula: C₉H₁₉N₃O₆

Molecular Weight: 265.26 g/mol

8.1 List of excipients

Water for injections

8.2 Incompatibilities

As no compatibility studies have been performed the medicinal product must not be mixed with other medicinal products.

8.3 Shelf life

Refer on pack

8.4 Special precautions for storage

Do not store above 25ºC.

Store in a cool & dark place.

Keep out of reach of children.

8.5 Packaging information

The concentrate to be made up into solution for infusion is presented in amber-coloured glass ampoules. An ampoule of 10 ml.

8.6 Special precautions for disposal

No special requirements.