Treatment of concomitant disease and sequelae due to impaired hepatic detoxification activity (e.g. in
cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy.

The dissolved contents of 1-2 sachets of Hepa-Merz granules are taken up to 3 times daily.
Hepa-Merz granules are dissolved in plenty of fluid (e.g. a glass of water, tea or juice) and taken with
or after meals.
The ready for use solution should be used immediately following preparation.
Paediatric population
The experiences on the use of the drug in children are limited (see chapter 4.4).

Hepa-Merz Granules contain fructose. Patients with rare hereditary problems of fructose intolerance
should not take this medicine.
Hepa-Merz granules contain 1.13 g fructose per sachet (equivalent to 0.11 CEU). This should be taken
into account in patients with diabetes mellitus.
Hepa-Merz granules may be harmful to the teeth (caries) in long-term use.
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.

No clinical data are available relating to intake of Hepa-Merz granules during pregnancy. No
exhaustive animal studies have been performed for L-ornithine-L-aspartate, to investigate its toxicity in
relation to reproduction. Administration of Hepa-Merz granules during pregnancy should therefore be
avoided. If, however, treatment with Hepa-Merz granules is considered necessary, careful
consideration should be given to the benefit versus risk ratio.
It is not known whether L-ornithine-L-aspartate is excreted into the breast milk. Administration of Hepa-
Merz granules should therefore be avoided during lactation. If, however, treatment with Hepa-Merz
granules is considered necessary, careful consideration should be given to the benefit versus risk ratio.
No data are available on the influence on fertility.

As a result of the disease, the ability to drive and use machines may be impaired during treatment with
L-ornithine-L-aspartate.

The frequency categories of undesirable effects 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
Gastrointestinal disorders
Uncommon: Nausea, vomiting, stomach ache, flatulence, diarrhoea.
Musculoskeletal and connective tissue disorders
Very rare: pain in the limbs
These undesirable effects are usually transient and do not require withdrawal of the medicine.
Orange yellow S (E 110) can trigger allergic reactions.

So far signs of intoxication have not been observed following an overdose of L-ornithine L-aspartate.
Symptomatic treatment is recommended if overdose occurs.

Pharmacotherapeutic group: Liver therapy, ATC code: A05BA
In vivo, L-ornithine-L-aspartate exerts its effects through the amino acids, ornithine and aspartate, via
two key methods of ammonia detoxification: urea synthesis and glutamine synthesis.
Urea synthesis takes place in the periportal hepatocytes. In these cells, ornithine serves both as an
activator of the enzymes ornithine-carbamoyltransferase and carbamoyl phosphate synthetase and
also as the substrate of urea synthesis.
Glutamine synthesis is localised in the perivenous hepatocytes. Particularly under pathological
conditions, aspartate and other dicarboxylates, including the metabolic products of ornithine, are
absorbed into the cells and used there to bind ammonia in the form of glutamine.
Glutamate is an amino acid that binds ammonia under both physiological and pathophysiological
conditions. The resulting amino acid glutamine not only represents 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.
Animal studies suggest that the ammonia-reducing effect of L-ornithine-L-aspartate is caused by
enhanced glutamine synthesis. Individual clinical studies have shown an improved branched-chain
amino acid/aromatic amino acid quotient.

L-ornithine-L-aspartate is rapidly absorbed and cleaved to form ornithine and aspartate. Both amino
acids have a short elimination half-life of 0.3 – 0.4 hours. A fraction of the aspartate is recovered in
unmetabolised form in the urine.

Preclinical data, based on safety pharmacological studies and chronic toxicity and mutagenicity
studies, do not suggest any particular risk to humans following correct administration.
No studies into any carcinogenic potential have been performed.
In a dose-finding study, L-ornithine-L-aspartate was insufficiently investigated in terms of its toxicity in
relation to reproduction.

Citric acid,
Saccharin sodium,
Sodium cyclamate,
Povidone 25,
Fructose,
lFavourings,
Orange yellow S (E 110).

Not applicable.

Do not store above 25ºC.
[For climatic zones III/IV: Do not store above 30ºC.]

Original packs are available containing 10, 30, 50, 100 and 250 sachets of granules for oral solution.
Not all pack sizes may be marketed.

No special requirements.