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Hepa-Merz® increases the detoxification capacity of the liver for the neurotoxin ammonia and lowers pathologically elevated ammonia levels. At the same time, an improvement in the mental state in patients with hepatic encephalopathy results.

Please also read:
Hepa-Merz® Clinical Trials

A significant lost of liver function results with diseases of the liver (e.g., liver cirrhosis). This not only affects the synthesis of important endogenous substances, but the detoxification of neurotoxic metabolic preparations in particular. Notably, due to the disordered urea and glutamine synthesis, the neurotoxin ammonia can reach the systemic circulation before it has been detoxified and lead to disorders in brain function which are also summarized under the term “hepatic encephalopathy”. L-ornithine-L-aspartate is capable of promoting the detoxification of ammonia by stimulation of urea and glutamine synthesis.

Urea synthesis takes place in the periportal hepatocytes. The enzymes necessary for this process, carbamoyl phosphate synthetase and ornithine carbamoyltransferase are activated by the provision of L-ornithine-L-aspartate. At the same time, ornithine serves as starting material for urea synthesis and is consequently involved in a number of ways in the activation of the urea cycle and thereby in the ultimate ammonia detoxification. Approximately one-third of the ammonia is ultimately detoxified by urea synthesis in healthy individuals because urea represents the final form of excretion for ammonia.

Glutamine synthesis is localized to the perivenous hepatocytes, also called scavenger cells. These scavenger cells possess the enzyme glutamine synthetase which exhibits a high affinity to ammonia and converts glutamate into nontoxic glutamine by coupling with ammonia. 
L-ornithine-L-aspartate supplies starting material for the synthesis of glutamine to the perivenous cells by providing aspartate and ornithine after their conversion into dicarboxylate. The glutamine formed is not only a nontoxic form of transport for ammonia, but also necessary at the same time for the activation of the urea cycle. Aspartate and dicarboxylate act as activators for disordered glutamine synthesis in persons with cirrhotic livers.

Please also read:
Mechanism of action of Hepa-Merz®

The following carrier solutions are suitable:

Secondary infusion

Glucose 5 %: a / b / c
Glucose 10 %: a / b / c
Sterofundin: a / b / c
Tutofusin: a / b / c
Ringer’s solution: a / b / c
Isotonic NaCl: a / b / c
Aminosteril N-Hepa: a / b / c
Comafusin Hepar: a / b / c

For compatibility testing, six ampules of Hepa-Merz® infusion solution concentrate were mixed with 450 ml of a carrier solution. The following parameters were tested at the start and at 2h, 5h and 24 h:

  • a) Color, appearance, pH, toxicity unchanged
  • b) No significant change in amino acid content (ornithine, aspartates); no significant formation of a degradation product (ornithine lactam) – tested using thin layer chromatography.
  • c) Compatibility with regard to the active substance from Hepa-Merz®

Hepa-Merz® infusion concentrate is indicated for the treatment of concomitant diseases and sequelae conditions due to disordered detoxification capacity of the liver (e.g., liver cirrhosis) with the symptoms of latent and manifest hepatic encephalopathy, particularly for the treatment of incipient consciousness disorders (precoma) or clouding of consciousness (coma). Up to 4 ampules per day are given as long as not indicated otherwise. Up to 8 ampules within 24 hours for incipient consciousness disorder (precoma) and clouding of consciousness (coma), depending on the severity of the condition.

Prior to use, the ampules are added to an infusion solution and infused in this form. Hepa-Merz® Infusion concentrate is easily miscible with the standard infusion bases. However, due to vein tolerability, not more than six ampules should be dissolved per 500 ml infusion.

The infusion speed is a maximum of 5 g ornithine-aspartate (equivalent to the content of one ampule) per hour.

Severe renal insufficiency (reference value: serum creatinine value > 3 mg/100 ml) is considered to be a contraindication.

Of the large number of test procedures used for the diagnosis of hepatic encephalopathy, the psychometric tests in particular, such as number connection tests, the line tracing test and the digit symbol test have emerged as sensitive and simple to perform tests for the recognition of HE. Also easy to perform is a writing sample with which the psychomotor skills are tested.

Please also read:
Psychometric test procedures

Hepa-Merz® – Summary of prescribing information

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, aspartame (E951), povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and 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 regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings: Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Aspartame (E951): Contains a source of phenylalanine. May be harmful for people with phenylketonuria. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Granules. Composition: One sachet with 5 g of Granules contains: Active substance: 3 g L-ornithine- L-aspartate. Excipients: citric acid, saccharin sodium, sodium cyclamate, povidone 25, fructose, flavorings, orange yellow S (E110). Note for diabetics: One sachet of Hepa-Merz® Granules contains 1.13 g of fructose (corresponds to approx. 0.11 BU). Therapeutic indications: Treatment of concomitant disease and sequelae due to impaired detoxification activity (e.g. in cirrhosis of the liver) with the symptoms of latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate, orange yellow S or any of the other excipients. Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 ml can be used as a guideline value. Relative: Pregnancy and lactation: No clinical data are available relating to intake of Hepa-Merz® Granules in children and 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 regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea, vomiting, stomach ache, flatulence, diarrhea. Very rare (< 1/10,000): Pain in the limbs. These undesirable effects are usually transient and do not require withdrawal of the medicine. Orange yellow S (E110) can trigger allergic reactions. Warnings : Hepa-Merz® Granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Further precautions: As a result of the disease, the ability to drive and operate machinery may be impaired during treatment with L-ornithine-L-aspartate.

Hepa-Merz® Infusion concentrate. Composition: One ampoule of 10 ml contains: Active substance: 5 g L-ornithine-L-aspartate. Excipients: Water for injections. Therapeutic indications: Latent and manifest hepatic encephalopathy. Contraindications: Absolute: Hypersensitivity to L-ornithine-L-aspartate. Severe renal impairment (renal failure). A serum creatinine level in excess of 3 mg/100 ml can be taken as a guide. Relative: Pregnancy and lactation: There are no clinical data available on the use of Hepa-Merz® Infusion concentrate in children and during pregnancy. L-ornithine L-aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies. The administration of Hepa-Merz® Infusion concentrate 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 regarding fertility. Undesirable effects: Uncommon (³ 1/1,000 to < 1/100): Nausea. Rare (³ 1/10,000 to < 1/1,000): vomiting. Frequency not known (frequency cannot be estimated from the available data): hypersensitivity, anaphylactic reaction. Generally however, the gastrointestinal symptoms are transient, and do not necessitate discontinuation of treatment. They disappear on reduction of the dose or the infusion rate. Further precautions: 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. At high doses of Hepa-Merz® 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. Depending on the underlying disease, the ability to drive and operate machines may also be impaired on treatment with L-ornithine L-aspartate. Hepa-Merz® Infusion concentrate must not be injected into an artery. Status: January 2016. Merz Pharmaceuticals GmbH, 60048 Frankfurt.