Latent and manifest hepatic encephalopathy.

Unless otherwise indicated, patients may be given up to 4 ampoules per day.
With incipient clouding of consciousness (precoma) or clouding of consciousness (coma), up to 8
ampoules may be given in 24 hours, depending on the severity of the condition.
The ampoules are added to an infusion solution before use, and infused in this form.
Hepa-Merz concentrate for solution for infusion can be mixed with the usual infusion solutions. So far no
peculiarities have been observed with regard to miscibility. However, the ampoules should be admixed
to the infusion solution only immediately before application. For venous tolerability, however, no more
than 6 ampoules should be dissolved per 500 ml infusion.
The maximum infusion rate is 5 g L-ornithine L-aspartate (corresponding to the content of 1 ampoule)
per hour.
Hepa-Merz concentrate for solution for infusion must not be administered into an artery.
Paediatric population
Experience in children is limited (see section 4.4).

At high doses of Hepa-Merz concentrate for solution for infusion, 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.
Paediatric population
No data are so far available on the use of the drug in children.

No interaction studies have been performed. Up to now interactions are not known.

There are no clinical data available on the use of Hepa-Merz concentrate for solution for infusion in
pregnancy.
L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in
experimental animal studies (see section 5.3). The administration of Hepa-Merz concentrate for solution
for infusion in pregnancy should therefore be avoided. If treatment with Hepa-Merz 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 Hepa-Merz
should therefore be avoided during lactation. If treatment with Hepa-Merz is nevertheless thought to be
necessary, the benefits and risks should be carefully assessed.
No data are available on the influence on fertility.

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

Based on clinical and post-marketing experience the information on the frequency of adverse reactions
is stated below. The frequency categories are defined 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
Not known: cannot be estimated from the available data
Immune system disorders
Not known: Hypersensitivity, anaphylactic reaction
Gastrointestinal disorders

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

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

Pharmacotherapeutic group : Liver therapy, ATC code: A05BA
In vivo, 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 animals point to increased glutamine synthesis as a mechanism of the
ammonia-lowering effect. Some clinical studies have shown an improvement in the ratio of branchedchain
to aromatic amino acids.

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.

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.

Water for injections

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

Do not store above 30ºC.

The concentrate to be made up into solution for infusion is presented in amber-coloured glass
ampoules.
Original packs containing 5, 10, 25 and 30 ampoules of 10 ml concentrate for solution for infusion.
Not all pack sizes may be marketed.

No special requirements.