Hepa-Merz

Granules: Each sachet contains: 3 g L-Ornithine-L-Aspartate.
Infusion: L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate is a clear solution.
One ampoule of 10 mL contains 5 g L-Ornithine-L-Aspartate.
Excipients/Inactive Ingredients: Granules: Citric acid, saccharin sodium, sodium cyclamate, povidone 25, flavourings, fructose, yellow orange S (E 110).
Infusion: Water for injection.

Pharmacotherapeutic group: Liver therapy. ATC code: A05BA.
Pharmacology: Pharmacodynamics: Granules: 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 localized 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.
Infusion: 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 localized in the perivenous hepatocytes. Under pathological conditions in particular, aspartate and other dicarboxylates - including metabolic products of ornithine - are taken up into 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 branched-chain to aromatic acids.
Pharmacokinetics: Granules: 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.
Infusion: 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.
Toxicology: Preclinical safety data: Granules: 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.
Infusion: 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.

Granules: For the 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.
Infusion: For the treatment of hyperammonemia as a result of acute and chronic liver disease such as liver cirrhosis, fatty liver, hepatitis, especially for the treatment of incipient disturbances of consciousness (precoma) or neurological complications (hepatic encephalopathy).

Granules: The dissolved contents of 1-2 sachets of L-Ornithine-L-Aspartate (Hepa-Merz) granules are taken up to 3 times daily. L-Ornithine-L-Aspartate (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 experience on the use of the drug in children are limited.
Infusion: 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. L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate 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. L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate must not be administered into an artery. Experience in children is limited (see Precautions).

So far signs of intoxication have not been observed following an overdose of L-Ornithine-L-Aspartate.
Granules: Symptomatic treatment is recommended if overdose occurs.
Infusion: Cases of overdose require symptomatic treatment.

Hypersensitivity to L-Ornithine-L-Aspartate.
Severely impaired renal function (renal insufficiency). A serum creatinine value over 3 mg/100 mL can be used as a guideline value.
Granules: Hypersensitivity to orange yellow S or any of the excipients.

Granules: L-Ornithine-L-Aspartate (Hepa-Merz) granules contain fructose. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
L-Ornithine-L-Aspartate (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.
L-Ornithine-L-Aspartate (Hepa-Merz) granules may be harmful to the teeth (caries) in long-term use.
Infusion: At high doses of L-Ornithine-L-Aspartate (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.
Effects on the 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.
Use in Children: No data are so far available on the use of the drug in children.

Granules: No clinical data are available relating to intake of L-Ornithine-L-Aspartate (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 L-Ornithine-L-Aspartate (Hepa-Merz) granules during pregnancy should therefore be avoided. If, however, treatment with L-Ornithine-L-Aspartate (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 breastmilk. Administration of L-Ornithine-L-Aspartate (Hepa-Merz) granules should therefore be avoided during lactation. If, however, treatment with L-Ornithine-L-Aspartate (Hepa-Merz) granules is considered necessary, careful consideration should be given to the benefit versus risk ratio.
Infusion: There are no clinical data available on the use of L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate in pregnancy. L-Ornithine-L-Aspartate has been investigated for reproduction toxicity only to a limited extent in experimental animal studies (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). The administration of L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate in pregnancy should therefore be avoided. If treatment with L-Ornithine-L-Aspartate (Hepa-Merz) infusion concentrate 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 breastmilk. Administration of L-Ornithine-L-Aspartate (Hepa-Merz) should therefore be avoided during lactation. If treatment with L-Ornithine-L-Aspartate (Hepa-Merz) is nevertheless thought to be necessary, the benefits and risks should be carefully assessed.

Granules: See Table 1.

Click on icon to see table/diagram/image

Gastrointestinal disorders: Uncommon: Nausea, vomiting, stomachache, flatulence, diarrhea.
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.
Infusion: Based on clinical and post-marketing experience the information on the frequency of adverse reactions is stated as follows. The frequency categories are defined as follows. (See Table 2.)

Click on icon to see table/diagram/image

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.

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

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

Store at temperatures not exceeding 30°C.
Shelf-life: Granules: 3 years.
Infusion: 36 months.

Cholagogues, Cholelitholytics & Hepatic Protectors

A05BA06 - ornithine oxoglurate ; Belongs to the class of drugs used in liver therapy.

Rx