FreAmine III

FREAMINE III- isoleucine, leucine, lysine acetate, methionine, phenylalanine, threonine, tryptophan, valine, alanine, arginine, histidine, proline, serine, glycine, cysteine hydrochloride and phosphoric acid injection, solution
B. Braun Medical Inc.

Protect from light until use.

DESCRIPTION

10% FreAmine® III (Amino Acid Injection) is a sterile, nonpyrogenic, hypertonic solution containing crystalline amino acids. Each 1000 mL provides a total of 15.3 g of nitrogen in 97 g of amino acids equal to 95.6 grams of protein equivalent. All amino acids designated USP are the “L”-isomer, with the exception of Glycine USP, which does not have an isomer.

Each 100 mL contains:

Essential amino acids

Isoleucine USP …………………………………………………… 0.69 g

Leucine USP ……………………………………………………… 0.91 g

Lysine USP ……………………………………………………….. 0.73 g

(added as Lysine Acetate USP ……………………………. 1.02 g)

Methionine USP …………………………………………………. 0.53 g

Phenylalanine USP ………………………………………………. 0.56 g

Threonine USP …………………………………………………… 0.40 g

Tryptophan USP ………………………………………………… 0.15 g

Valine USP ……………………………………………………….. 0.66 g

Nonessential amino acids

Alanine USP ……………………………………………………… 0.71 g

Arginine USP …………………………………………………….. 0.95 g

Histidine USP ……………………………………………………. 0.28 g

Proline USP ……………………………………………………… 1.12 g

Serine USP ……………………………………………………….. 0.59 g

Glycine USP ……………………………………………………… 1.40 g

Cysteine ………………………………………………………….. <0.016 g

(as Cysteine HCl•H₂ O USP …………………………….. <0.024 g)

Phosphoric Acid NF…………………………………………… 0.12 g

Sodium Bisulfite (as an antioxidant) ……………………….. <0.10 g

Water for Injection USP ………………………………………. qs

pH adjusted with Glacial Acetic Acid USP
pH: 6.5 (6.0 – 7.0)
Calculated Osmolarity: 950 mOsmol/liter

Concentration of Electrolytes (mEq/liter): Sodium 10
Phosphate (HPO) 20 (10 mmole P/liter); Acetate Approx. 89(provided as acetic acid and lysine acetate); Chloride <3.

CLINICAL PHARMACOLOGY

10% FreAmine® III provides a physiological ratio of biologically utilizable amino acids in concentrated form for protein synthesis. Used with concentrated calorie sources such as hypertonic dextrose or fat emulsion, and with electrolytes, vitamins and minerals, it provides total parenteral nutrition. Administered peripherally as an isotonic solution (3%) without nonprotein calories or with minimal caloric supplementation such as 5% dextrose, it provides nutritional support and spares body protein.

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 condition 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 amounts of sodium and chloride present are not of clinical significance.

INDICATIONS AND USAGE

Parenteral nutrition with 10% FreAmine® III (Amino Acid Injection) is indicated to prevent nitrogen loss or treat negative nitrogen balance in adults and pediatric patients where (1) the alimentary tract, by the oral, gastrostomy, or jejunostomy route, cannot or should not be used, or adequate protein intake is not feasible by these routes; (2) gastrointestinal absorption of protein is impaired; or (3) protein requirements are substantially increased as with extensive burns. Dosage, route of administration, and concomitant infusion of nonprotein calories are dependent on various factors, such as nutritional and metabolic status of the patient, anticipated duration of parenteral nutritional support, and vein tolerance. See WARNINGS, PRECAUTIONS, Pediatric Use, and DOSAGE AND ADMINISTRATION.

Central Venous Nutrition

Central venous infusion should be considered when amino acid solutions are to be admixed with hypertonic dextrose to promote protein synthesis in hypercatabolic or severely depleted patients, or those requiring long-term parenteral nutrition.

Peripheral Parenteral Nutrition

For moderately catabolic or depleted patients in whom the central venous route is not indicated, diluted amino acid solutions mixed with 5% dextrose solutions may be infused by peripheral vein, supplemented, if desired, with fat emulsion. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).

Protein Sparing

In well-nourished, mildly catabolic patients such as routine postsurgical patients who require only short-term parenteral nutrition, protein sparing can be achieved by peripheral infusion of amino acid solutions with or without dextrose.

CONTRAINDICATIONS

10% FreAmine® III is contraindicated in patients with anuria, hepatic coma, inborn errors of amino acid metabolism, or hypersensitivity to one or more amino acids present in the solution.

WARNINGS

This product contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

Safe and effective use of central venous nutrition requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of the complications which can occur. Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of central venous nutrition. Laboratory tests should include measurement of blood sugar, electrolyte, and serum protein concentrations; kidney and liver function tests; and evaluation of acid-base balance and fluid balance. Other laboratory tests may be suggested by the patient’s condition.

The intravenous administration of these solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the solute concentration of the solution infused. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the concentration of the solution.

Administration of amino acids in the presence of impaired renal function or gastrointestinal bleeding may augment an already elevated blood urea nitrogen. Patients with azotemia from any cause should not be infused with amino acids without regard to total nitrogen intake.

Administration of amino acid solutions to a patient with hepatic insufficiency may result in plasma amino acid imbalances, hyperammonemia, prerenal azotemia, stupor and coma.

Hyperammonemia is of special significance in infants as its occurrence in the syndrome caused by genetic metabolic defects is sometimes associated, although not necessarily in a causal relationship, with mental retardation. This reaction appears to be dose related and is more likely to develop during prolonged therapy. It is essential that blood ammonia be measured frequently in infants. The mechanisms of this reaction are not clearly defined but may involve genetic defects and immature or subclinically impaired liver function.

Conservative doses of amino acids should be given, dictated by the nutritional status of the patient. Should symptoms of hyperammonemia develop, amino acid administration should be discontinued and the patient’s clinical status reevaluated.