HEPATASOL- leucine, isoleucine, valine, lysine, threonine, methionine, phenylalanine, tryptophan, glycine, proline, alanine, arginine, serine, histidine and cysteine hydrochloride injection
Baxter Healthcare Corporation
DESCRIPTION
8% HEPATASOL � sulfite-free (Amino Acid) Injection is a sterile, nonpyrogenic, hypertonic solution containing crystalline amino acids.
The VIAFLEX plastic container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). Exposure to temperatures above 25�C/77�F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period. The amount of water that can permeate from inside the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period (e.g., di-2-ethylhexyl phthalate, DEHP, at not more than 0.2 part per million); however, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by tissue culture toxicity studies.
Intravenous fat emulsion should not be administered in polyvinyl chloride (PVC) containers that use di-2-ethylhexyl phthalate (DEHP) as a plasticizer, because the fat emulsion facilitates the leaching of DEHP from these containers.
Each 100 mL contains:
Amino Acids 8 g
Total Nitrogen 1.22 g
Essential Amino Acids
Leucine � (CH3 )2 CHCH2 CH (NH2 ) COOH 1.10 g
Isoleucine � CH3 CH2 CH (CH3 ) CH (NH2 ) COOH 0.90 g
Valine � (CH3 )2 CHCH (NH2 ) COOH 0.84 g
Lysine � (added as lysine acetate) H2 N (CH2 )4 CH (NH2 ) COOH 0.61 g
Threonine � CH3 CH (OH) CH (NH2 ) COOH 0.45 g
Methionine � CH3 S (CH2 )2 CH (NH2 ) COOH 0.10 g
Phenylalanine � (C6 H5 ) CH2 CH (NH2 ) COOH 0.10 g
Tryptophan � (C8 H6 N) CH2 CH (NH2 ) COOH 0.066 g
Nonessential Amino Acids
Glycine � H2 NCH2 COOH 0.90 g
Proline � [(CH2 )3 NH CH] COOH 0.80 g
Alanine � CH3 CH (NH2 ) COOH 0.77 g
Arginine � H2 NC (NH) NH (CH2 )3 CH (NH2 ) COOH 0.60 g
Serine � HOCH2 CH (NH2 ) COOH 0.50 g
Histidine � (C3 H3 N2 ) CH2 CH (NH2 ) COOH 0.24 g
Cysteine Hydrochloride Monohydrate � [SHCH2 CHNH2 COOH]�HCl�H2 O less than 0.020 g
Phosphoric Acid NF 0.115 g
pH (pH adjusted with glacial acetic acid) 6.5 (6.0 to 6.8)
Electrolyte profile mEq per liter*
Chloride less than 3, Phosphate (as HPO4 =) 20 (10 mmoles/Liter), Acetate 68 (provided as glacial acetic acid and lysine acetate).
*Balanced by ions from amino acids.
Osmolarity (Calc.) 775 mOsmol/L
CLINICAL PHARMACOLOGY
8% HEPATASOL � sulfite-free (Amino Acid) Injection provides a mixture of essential and nonessential amino acids with high concentrations of the branched chain amino acids isoleucine, leucine, and valine, and low concentrations of methionine and the aromatic amino acids phenylalanine and tryptophan, relative to general purpose amino acid injections. This amino acid composition has been specifically formulated to provide a well tolerated nitrogen source for nutritional support and therapy of patients with liver disease who have hepatic encephalopathy.
The precise mechanisms which produce the therapeutic effects of this amino acid formulation are not known, The etiopathology of hepatic encephalopathy is also unknown and is thought to be of multifactorial origin. The rationale for this amino acid formulation is based on observations of plasma amino acid imbalances in patients with liver disease and on theories which postulate that these abnormal patterns are causally related to the development of hepatic encephalopathy.
Clinical studies in patients with hepatic encephalopathy showed that the infusion of this amino acid formulation reversed the abnormal plasma amino acid pattern characterized by decreased levels of branched chain amino acids and elevated levels of aromatic amino acids and methionine. The trend toward normalization of these amino acids was generally associated with an improvement in mental status and EEG patterns. This clinical response was observed in the majority of patients studied. Nitrogen balance was significantly improved and mortality reduced in these typically protein-intolerant patients who received substantial amounts of protein equivalent as this amino acid injection.
When infused with hypertonic dextrose as a calorie source, supplemented with electrolytes, vitamins, and minerals, this amino acid formulation provides total parenteral nutrition in patients with liver disease, with the exception of essential fatty acids.
Phosphate is a major intracellular anion which participates in providing energy for metabolism of substrates and contributes to significant metabolic and enzymatic reactions in all organs and tissues. It exerts a modifying influence on calcium levels, a buffering effect on acid-base equilibrium, and has a primary role in the renal excretion of hydrogen ions.
It is thought that the acetate from lysine acetate and acetic acid, under the conditions of parenteral nutrition, does not impact net acid-base balance when renal and respiratory functions are normal. Clinical evidence seems to support this thinking; however, confirmatory experimental evidence is not available.
The amount of chloride present is not of clinical significance.
INDICATIONS AND USAGE
8% HEPATASOL � sulfite-free (Amino Acid) Injection is indicated for the treatment of hepatic encephalopathy in patients with cirrhosis or hepatitis. 8% HEPATASOL � sulfite-free (Amino Acid) Injection provides nutritional support for patients with these diseases of the liver who require parenteral nutrition and are intolerant of general purpose amino acid injections, which are contraindicated in patients with hepatic coma.
