Protect from light until use.

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•H2O 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.

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.

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.

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.

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.

See "WARNINGS" and "Special Precautions for Central Venous Nutrition."

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation and hypervolemia.

Local reactions of the infusion site, consisting of a warm sensation, erythema, phlebitis and thrombosis, have been reported with peripheral amino acid infusions, especially if other substances are also administered through the same site.

Generalized flushing, fever and nausea have been reported during peripheral administration of amino acids.

Symptoms may result from an excess or deficit of one or more of the ions present in the solution; therefore, frequent monitoring of electrolyte levels is essential.

If electrolyte supplementation is required during peripheral infusion, it is recommended that additives be administered throughout the day in order to avoid possible venous irritation. Irritating additive medications may require injection at another site and should not be added directly to the amino acid infusate.

Phosphorus deficiency may lead to impaired tissue oxygenation and acute hemolytic anemia. Relative to calcium, excessive phosphorus intake can precipitate hypocalcemia with cramps, tetany and muscular hyperexcitability.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient's condition, and institute appropriate corrective treatment.

The total daily dose of 10% FreAmine® III (Amino Acid Injection) depends on daily protein requirements and on the patient's metabolic and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual protein requirements.

While Recommended Dietary Allowances of protein are approximately 0.8 g/kg of body weight for a healthy adult and 1.4 to 2.2 g/kg for healthy growing infants and pediatric patients. It must be recognized that protein as well as caloric requirements in traumatized or malnourished patients may be substantially increased. Daily amino acid doses of approximately 1.5 g/kg of body weight for adults and 2 to 3 g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Higher doses may be required in severely catabolic states. Such higher doses, especially in infants, must be accompanied by frequent laboratory evaluation. Fat emulsion may be supplied to help meet energy requirements.

Fat emulsion coadministration should be considered when prolonged (more than 5 days) parenteral nutrition is required in order to prevent essential fatty acid deficiency (E.F.A.D.). Serum lipids should be monitored for evidence of E.F.A.D. in patients maintained on fat free TPN.

For protein sparing in well-nourished patients not receiving significant additional calories, amino acid dosages of 1.0 to 1.7 g/kg/day significantly reduce nitrogen losses and spare body protein. If rises in BUN exceed 20 mg% in 48 hours, amino acid infusion should be discontinued or rate of administration reduced.

The provision of sufficient intracellular electrolytes, principally potassium, magnesium, and phosphate, is also required for optimum utilization of amino acids. Approximately 60–180 mEq of potassium, 10–30 mEq of magnesium, and 20–80 mEq of phosphate per day appear necessary to achieve optimum metabolic response. In addition, sufficient quantities of the major extracellular electrolytes (sodium, calcium, and chloride) must be given. In patients with hyperchloremic or other metabolic acidoses, sodium and potassium may be added as the acetate or lactate salts to provide bicarbonate precursor. The electrolyte content of 10% FreAmine® III (Amino Acid Injection) must be considered when calculating daily electrolyte intake. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently.

If a patient's nutritional intake is primarily parenteral, vitamins, especially the water soluble vitamins, and trace elements should also be provided.

For severely catabolic, depleted patients or those requiring long-term total parenteral nutrition, central venous nutrition should be considered. Calorie-to-nitrogen ratios of at least 100 to 150 nonprotein calories per gram of nitrogen have been recommended to achieve positive nitrogen balance in such patients. These ratios are easily and conveniently attained with the use of concentrated dextrose solutions, supplemented if desired with parenteral fat emulsion.

Total parenteral nutrition may be started with infusates containing lower concentrations of dextrose; dextrose content may be gradually increased to estimated caloric needs as the patient's glucose tolerance increases.

In adults, strongly hypertonic mixtures of amino acids and dextrose may be safely administered only by continuous infusion through a central venous catheter with the tip located in the vena cava. For optimal nitrogen utilization, 500 mL of 10% FreAmine® III appropriately mixed with concentrated dextrose, electrolytes, and vitamins are typically administered over an 8-hour period. If administration rate should fall behind schedule, no attempt to "catch up" to planned intake should be made. In addition to meeting protein needs, the administration rate is also governed, especially during the first few days of therapy by the patient's glucose tolerance. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determination of urine and blood sugar levels. In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria. To prevent rebound hypoglycemia, a solution containing 5% dextrose should be administered when hypertonic dextrose infusions are abruptly discontinued.

For moderately catabolic, depleted patients requiring parenteral nutrition in whom the central venous route is not indicated, 10% FreAmine® III can be mixed with 5% dextrose solutions and administered by peripheral vein. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L).

Fat provides approximately 9 kcal per gram and parenteral fat emulsion may be administered along with amino acid-dextrose solutions through a Y-type administration set to supplement caloric intake. Fat, however, should not be the sole caloric intake since some studies have suggested that glucose is more nitrogen sparing in the stressed patient.

For well-nourished, mildly catabolic patients who require short-term parenteral nutritional support, 10% FreAmine® III can be administered peripherally with or without parenteral carbohydrate calories. Such infusates can be prepared by dilution of 10% FreAmine® III with Sterile Water for Injection USP or 5% Dextrose Injection USP solutions to prepare isotonic or slightly hypertonic solutions which may be administered by peripheral vein.

Use of 10% FreAmine® III in pediatric patients is governed by the same considerations that affect the use of any amino acid solution in pediatrics. The amount administered is dosed on the basis of grams of amino acids/kg of body weight/day. Two to three g/kg of body weight for infants with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. Solutions administered by peripheral vein should not exceed twice normal serum osmolarity (718 mOsmol/L).

Infants (up to 10 kg) on total parenteral nutrition generally receive 2 to 3 grams of protein, 120 to 150 calories, and 120 to 150 mL of fluid per kilogram of body weight per day. This can be provided in a solution containing approximately 2-1/8% FreAmine® III (diluted from 10% FreAmine® III (Amino Acid Injection) and 20% dextrose. Less hypertonic mixtures may be administered by peripheral vein. Fat emulsion may be given concurrently by central or peripheral vein through a Y-type administration set to provide essential fatty acids and increase caloric intake. Since physiological changes occur rapidly in small infants, the daily dose of nutrients should initially be increased slowly with frequent monitoring of pertinent clinical and metabolic parameters. Pediatric patients over 10 kilograms require fewer calories and slightly less protein; generally 50 to 80 calories and 2 grams of protein per kilogram per day is sufficient.

See INDICATIONS AND USAGE, WARNINGS, and PRECAUTIONS, Pediatric Use.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Care must be taken to avoid incompatible admixtures. Consult with pharmacist.

10% FreAmine® III is supplied sterile and nonpyrogenic in glass intravenous infusion bottles with solid stoppers. The 1000 mL containers are packed 6 per case.

Rx only

Revised: August 2019

FreAmine is a registered trademark of B. Braun Medical Inc.

Designed for use with a vented set. Use 18 to 22 gauge needle size for admixing or withdrawing solutions from the glass bottle.

Before use, perform the following checks:

1. Inspect each container. Read the label. Ensure solution is the one ordered and is within the expiration date.
2. Invert container and carefully inspect the solution in good light for cloudiness, haze, or particulate matter; check the bottle for cracks or other damage. In checking for cracks, do not be confused by normal surface marks and seams on the bottom and sides of the bottle. These are not flaws. Look for bright reflections that have depth and penetrate into the wall of the bottle. Reject any such bottle.
3. Remove plastic cap (see Figure 1).
   
   
   
4. Swab exposed stopper surface with a suitable disinfectant.
   
   Warning: Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.
5. When adding medication to the container prior to administration, swab the target area of the rubber stopper, inject medication and mix thoroughly by gentle agitation.
6. Refer to Directions for Use of the set being used. Insert the set spike into the bottle through the target area of the rubber stopper. Allow the fluid to flow and remove air from the tubing before administration begins. Hang the container.
7. After admixture and during administration, re-inspect the solution frequently. If any evidence of solution contamination or instability is found or if the patient exhibits any signs of fever, chills or other reactions not readily explainable, discontinue administration immediately and notify the physician.
8. Spiking, additions, or transfers should be made immediately after swabbing stopper surface. Check for vacuum at first puncture of stopper. Admixture by needle or syringe should be made through the target area of the rubber stopper; contents should be drawn by vacuum into the bottle. Admixture by spiked vial should also be through the target area of the rubber stopper (see Figure 2). If contents of initial addition are not drawn into the bottle, vacuum is not present and the unit should be discarded. Each addition/transfer will reduce the vacuum remaining in the bottle.
   
   
   
9. If the first puncture of the stopper is the administration set spike, insert the spike fully into the target area of the rubber stopper and promptly invert the bottle. Verify vacuum by observing rising air bubbles. Do not use the bottle if vacuum is not present.
10. If admixture or set insertion is not performed immediately following swabbing, swab stopper surface again with a suitable disinfectant.

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Y36-003-006  LD-425-4

10% FreAmine® III

(Amino Acid Injection)

REF S9010-SS

NDC 0264-9010-55

1000 mL

Protect from light until use.

Each 100 mL contains:

Essential amino acids — Isoleucine USP 0.69 g

Leucine USP 0.91 g; Lysine 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•H2O USP <0.024 g)

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Phosphoric Acid NF 0.12 g

Sodium Bisulfite (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

Electrolytes (mEq/liter): Sodium 10

Phosphate (HPO ) 20 (10 mmole P/liter)

Acetate 89 (see Package Insert) Chloride <3

Sterile, nonpyrogenic. Single dose container.

For intravenous use only. Use only if solution

is clear and vacuum is present.

Recommended Storage:

Room temperature (25°C). Avoid excessive heat. Protect from freezing.

See Package Insert.

Rx only

FreAmine is a registered trademark of B. Braun Medical Inc.

Y37-002-546   LD-357-2

10% FreAmine® III

(Amino Acid Injection)

REF S9010-SS

NDC 0264-9010-55

1000 mL

Protect from light until use.

Each 100 mL contains:

Essential amino acids –

Isoleucine USP 0.69 g; Leucine USP 0.91 g

Lysine 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•H2O USP <0.024 g)

Phosphoric Acid NF 0.12 g

Sodium Bisulfite (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

Electrolytes (mEq/liter):

Sodium 10

Phosphate (HPO) 20 (10 mmole P/liter)

Acetate 89 (see Package Insert)

Chloride <3

See adjacent panel for further product information.

B. Braun Medical Inc.

Bethlehem, PA 18018-3524 USA

1-800-227-2862

Sterile, nonpyrogenic. Single dose container.

For intravenous use only.

Use only if solution is clear and vacuum is present.

Recommended Storage:

Room temperature (25°C). Avoid excessive heat.

Protect from freezing. See Package Insert.

Rx only

FreAmine is a registered trademark of B. Braun Medical Inc.

X12-002-487 LD-612-1