Aminoleban

Each 500 mL of AMINOLEBAN contains the following ingredients: see table.

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Etiologically the onset of hepatic encephalopathy has been related to excess ammonia, short-chain fatty acids and mercaptans. Recent studies have emphasized the importance of other contributory factors involved in severe hepatic impairment: disturbance of the free amino acid pattern in plasma characterized by an increase of L-Phenylalanine, L-Tryptophan, L-Tyrosine and L-Methionine and a decrease of branched-chain amino acids such as L-Leucine, L-Isoleucine and L-Valine.
The disturbance of the free plasma amino acid pattern causes disturbances in the transport of amino acid across the blood-brain barrier, blocks synthesis of false neurotransmitters in the brain, resulting in the disturbance of the overall cerebral amine metabolism. This disturbance of cerebral amine metabolism is suspected to be the major cause of hepatic encephalopathy.
With these findings as background information, Fischer et al developed a special formula of amino acids, containing high concentrations of branched-chain amino acids and low concentrations of L-Phenylalanine, L-Tryptophan and L-Methionine, without L-Tyrosine, to correct the disturbance of the plasma free amino acid pattern. They have conducted experimental and clinical studies of the special formula for the treatment of hepatic encephalopathy and demonstrated that the normalization of the plasma free amino acid pattern is effective in improving hepatic encephalopathy.
AMINOLEBAN is prepared with an amino acid composition identical to that of Fischer's formula. Clinical studies have shown that the injection is effective in correcting plasma amino acid concentrations and the clinical symptoms of hepatic encephalopathy.
pH: Approx 5.9 (mean obtained immediately after manufacture) and 5.5 - 6.5 (specification).
Specific gravity (20°C): 1.025.
Osmolarity: Approx. 768 mOsm/L.
Excipients/Inactive Ingredients: Sodium bisulfite 0.3 g/L is used as a stabilizer.

Pharmacology: AMINOLEBAN normalized the pattern of free amino acids in the plasma and brain, improved serotonin metabolism in the brain and corrected a sleep-wakefulness pattern in a rat model of chronic hepatic insufficiency which underwent a portacaval shunt operation.
When infused to portacaval-shunted rats loaded with ammonia, AMINOLEBAN improved EEG pattern and corrected amine metabolism in the brain as evidenced by correction of the free amino acid pattern in the plasma and brain and by suppression of an increase of the false neurotransmitter octopamine.

Treatment of hepatic encephalopathy in patients with chronic liver disease.

The usual adult dose of AMINOLEBAN is 500-1000 mL per dose by intravenous drip infusion. The usual peripheral infusion rate is 500 mL over 180-300 minutes in adults (approx. 25-40 drops per minute). For total parenteral nutrition, 500-1000 mL of the injection should be suitable combined with dextrose or other solutions and administered over 24 hours via the central vein. The dosage may be adjusted depending on the patient's age, symptoms and body weight.

Hyperammonemia has been reported after the administration of amino acid preparations, including this solution, in combination with oral intake of nitrogen (total nitrogen dose: 160 g). (See Clinically significant adverse reactions under Adverse Reactions).

This product is contraindicated in the following patients: Patients with severe renal disorder. (The amount of water tends to be excessive and the patient's clinical condition may be worsened. Urea and other amino acid metabolites may be retained, which may worsen the patient's clinical condition).
Patients with abnormal amino acid metabolism. (Since the infused amino acids are not adequately metabolized, the patient's clinical condition may be worsened).

This product should be administered with caution in the following patients: Patients with severe acidosis. (The patient's clinical condition may be worsened.)
Patients with congestive cardiac failure. (Any increase in the circulating blood volume may worsen the patient's clinical condition.)
Before administration: To prevent associated infection, carry out all procedures under aseptic conditions.
Use the solution after warming to near body temperature during cold environmental conditions.
Use the solution immediately after opening the package. After use, discard all unused solution.
During administration: The solution contains about 12 mEq/L of sodium and 94 mEq/L chloride. Concomitant use with an electrolyte solution or a large dose require careful monitoring of electrolyte balance.
Administer slowly via a peripheral vein.
When vascular pain occurs, use an alternate site or discontinue the administration.
Use in Children: Safety in children has not been established.
Use in the Elderly: Since elderly patients often have a reduced physiological function, it is advisable to take such measures as reducing the dose by decreasing the infusion rate.

(Rarely: < 0.1%, infrequently: 0.1% - < 5% no specific designation: 5% of frequency unknown.)
Clinically significant adverse reactions: Hypoglycemia: Hypoglycemia may occur. If the patient develops hypoglycemia, glucose should be administered promptly by intravenous infusion. In addition, appropriate nutrition management is required in such patients.
Hyperammonemia: Hyperammonemia has been reported. If the patient develops persistent hyperammonemia during the administration of AMINOLEBAN, discontinue administration and take measures to eliminate other nitrogen sources.
Other adverse reactions: Hypersensitivity: Symptoms such as skin rash may occur rarely. In the event of skin rash, discontinue the administration and institute appropriate treatment.
Gastrointestinal: Symptoms such as nausea and vomiting may occur infrequently.
Cardiovascular: Symptoms such as chest discomfort and palpitation may occur infrequently.
Metabolic: The nitrogen content of this preparation may induce a transient increase in blood ammonia concentrations.
Large dose and rapid administration: Acidosis may occur when large doses are administered rapidly.
Others: Chills, fever, headache and vascular pain may infrequently occur.

PRECAUTION FOR HANDLING: 1. A crystalline precipitate may form due to temperature changes during storage. Shake the solution at temperature of 15-25°C to dissolve precipitate before use and after cooling to near body temperature.
2. Do not use the product if the solution is discolored or a precipitate that cannot be dissolved by shaking has formed.
3. Open the outer wrap just before use.
4. Do not use if bag is leaking, solution cloudy or contains foreign matters.

Store below 30°C, protect from light.

Parenteral Nutritional Products

B05BA01 - amino acids ; Belongs to the class of solutions for parenteral nutrition used in I.V. solutions.

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