SPL UNCLASSIFIED SECTION.


Baxter Healthcare Corporation Clintec Nutrition Division Deerfield, IL 60015 USA Printed in USA 07-19-72-997 Rev. April 2014 BAXTER, PROSOL, VIAFLEX, and PL 146 are trademarks of Baxter International Inc.

HOW SUPPLIED SECTION.


HOW SUPPLIED 20% PROSOL - sulfite-free (Amino Acid) Injection is supplied in VIAFLEX plastic Pharmacy Bulk Package containers in the following sizes: 2B6183 500 mL NDC 0338-0499-03 2B6184 1000 mL NDC 0338-0499-04 2B6186 2000 mL NDC 0338-0499-06 Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended the product be stored at room temperature (25C/77F): brief exposure up to 40C/104F does not adversely affect the product. Do not remove container from overpouch until ready to use. Do not use if overpouch has been previously opened or damaged.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PRINCIPAL DISPLAY PANEL Container Label Container Label LOT EXP 2B6186 2000 mL NDC 0338-0499-06 20% ProSol - sulfite-free 20% (Amino Acid) Injection Pharmacy Bulk Package Not For Direct Infusion Rx Only EACH 100 mL CONTAINS ESSENTIAL AMINO ACIDS VALINE 1.44 g LYSINE (ADDED AS LYSINE ACETATE) 1.35 g HISTIDINE 1.18 g ISOLEUCINE 1.08 g LEUCINE 1.08 g PHENYLALANINE 1.00 g THREONINE 980 mg METHIONINE 760 mg TRYPTOPHAN 320 mg NONESSENTIAL AMINO ACIDS ALANINE 2.76 g GLYCINE 2.06 g ARGININE 1.96 g PROLINE 1.34 g GLUTAMIC ACID 1.02 g SERINE 1.02 g ASPARTIC ACID 600 mg TYROSINE 50 mg pH ADJUSTED WITH GLACIAL ACETIC ACID pH 6.0 (5.5 TO 6.5) mEq/L* ACETATE 140 *BALANCED BY IONS FROM AMINO ACIDS HYPERTONIC OSMOLARITY 1835 mOsmol/L (CALC) STERILE NONPYROGENIC CONTAINS NO MORE THAN 25 g/L OF ALUMINUM ADDITIVES MAY BE INCOMPATIBLE CONSULT WITH PHARMACIST IF AVAILABLE WHEN COMPOUNDING ADMIXTURES USE ASEPTIC TECHNIQUE MIX THOROUGHLY DO NOT STORE DOSAGE ADMIX FOR INTRAVENOUS ADMINISTRATION AS DIRECTED BY A PHYSICIAN SEE ACCOMPANYING DIRECTIONS FOR USE ONCE CONTAINER CLOSURE HAS BEEN PENETRATED WITHDRAWAL OF CONTENTS SHOULD BE COMPLETED WITHIN 4 HOURS AFFIX ACCOMPANYING LABEL FOR DATE AND TIME OF ENTRY STORE AT ROOM TEMPERATURE (25C/77F) CAUTION DO NOT USE UNLESS SOLUTION IS CLEAR AND SEAL IS INTACT A SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THE PRODUCT VIAFLEX CONTAINER PL 146 PLASTIC VIAFLEX CONTAINER PL 146 PLASTIC Baxter Logo BAXTER HEALTHCARE CORPORATION CLINTEC NUTRITION DIVISION DEERFIELD, IL 60015 USA MADE IN USA BAXTER, PROSOL, VIAFLEX AND PL 146 ARE TRADEMARKS OF BAXTER INTERNATIONAL INC US PATENT NO 5 206 269 1800 1600 1400 1200 1000 800 600 400 Carton Label Carton Label Lot: xx QTY: 6-2000 mL Exp: x x Code: 2B6186 NDC: 0338-0499-06 20% Prosol - Sulfite-Free (Amino Acid) INJ Viaflex Container (17) XX00 (10) xx (01) 50303380499064 07/31/09 10:18:13 07-35-C

ADVERSE REACTIONS SECTION.


ADVERSE REACTIONS See WARNINGS, PRECAUTIONS and SPECIAL PRECAUTIONS Infusion of any hypertonic solution can result in local inflammatory reactions. Policies and procedures should be established for the recognition and management of such reactions.

INDICATIONS & USAGE SECTION.


INDICATIONS AND USAGE 20% PROSOL - sulfite-free (Amino Acid) Injection is indicated as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance in patients where: (1) the alimentary tract cannot or should not be used, (2) gastrointestinal absorption of protein is impaired, or (3) metabolic requirements for protein are substantially increased, as with extensive burns. 20% PROSOL - sulfite-free (Amino Acid) Injection can be used to reduce fluid intake in patients who require both fluid restriction and total parenteral nutrition (TPN). 20% PROSOL - sulfite-free (Amino Acid) Injection is intended to be dosed on the basis of grams of amino acids/kg body weight/day. Therefore, this more concentrated amino acid solution provides the same nutritional value (grams of total amino acids) as in a more dilute form, but with the opportunity to limit fluid intake. Central Vein Administration: 20% PROSOL - sulfite-free (Amino Acid) Injection is intended for use in a pharmacy admixture program and as such is restricted to the preparation of admixtures for intravenous use. Central vein infusion should be considered when amino acid solutions are to be admixed with hypertonic dextrose to promote protein synthesis such as for hypercatabolic or depleted patients or those requiring long term parenteral nutrition. 20% PROSOL - sulfite-free (Amino Acid) Injection should never be administered undiluted. Peripheral Vein Administration: For patients in whom the central vein route is not indicated, amino acid solutions diluted with low dextrose concentrations may be infused by peripheral vein with or without supplemented fat emulsion. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L). 20% PROSOL - sulfite-free (Amino Acid) Injection should never be administered by peripheral vein undiluted. Protein-Sparing: Dilute amino acid solutions for peripheral administration may be used in patients who exhibit no clinically significant protein malnutrition. The purpose of the solution is to replace protein losses which occur in relation to an intercurrent phenomenon which is known or suspected to be productive of a protein loss condition for a short or moderate period of time. Protein-sparing can be achieved by peripheral infusion of dilute amino acid solutions with or without dextrose. 20% PROSOL - sulfite-free (Amino Acid) Injection must be diluted below twice normal serum osmolarity (718 mOsmol/L).

DOSAGE & ADMINISTRATION SECTION.


DOSAGE AND ADMINISTRATION If a patient is unable to take enteral nourishment for a prolonged period of time, institution of total parenteral nutrition (TPN) with exogenous calories should be considered. The total daily dose of 20% PROSOL sulfite-free (Amino Acid) Injection depends on the patients metabolic requirement 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 nitrogen requirements. Recommended Dietary Allowances* of protein range from approximately 0.75 g/kg of body weight for adults to 1.68 g/kg for infants. It must be recognized, however, that protein as well as caloric requirements in traumatized or malnourished patients may be increased substantially. Daily amino acid doses of approximately 1.0 to 1.5 g/kg of body weight for adults with adequate calories are generally sufficient to satisfy protein needs and promote positive nitrogen balance. For the initial treatment of trauma or protein calorie malnutrition, higher doses of protein with corresponding quantities of carbohydrate may be necessary to promote adequate patient response to therapy. The severity of the illness being treated is the primary consideration in determining proper dose level. Such higher doses, especially in infants, must be accompanied by more frequent laboratory evaluation. For protein-sparing in well nourished patients not receiving significant additional calories, amino acid dosages of 1.0 to 1.7 g/kg/day reduce nitrogen losses and spare body protein. If daily increases in BUN in the range of 10 to 15 mg% for more than three days should occur, then protein-sparing therapy should be discontinued and a regimen with full nonprotein calorie substrates should be adopted. *Food and Nutrition Board National Academy of Sciences - National Research Council (Revised 1989) Care should be exercised to insure the maintenance of proper levels of serum potassium. Quantities of 60 to 180 mEq of potassium per day have been used with adequate clinical effect. It may be necessary to add quantities of this electrolyte to this injection, depending primarily on the amount of carbohydrate administered to and metabolized by the patient. Total daily fluid requirements can be met beyond the volume of amino acid solutions by supplementing with noncarbohydrate or carbohydrate-containing electrolyte solutions. Maintenance vitamins, additional electrolytes and trace elements should be administered as required. Fat emulsion coadministration should be considered when prolonged parenteral nutrition (more than 5 days) is required in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat free total parenteral nutrition. Caution should be exercised in administering fat emulsions to patients with severe liver damage, pulmonary disease, anemia or blood coagulation disorders, or when there is danger of fat embolism. Fat emulsion admixed into total parenteral formula may obscure the presence of precipitate formation. Central Vein Administration: Hypertonic mixtures of amino acids and dextrose may be administered safely by continuous infusion through a central venous catheter with the tip located in the vena cava. In addition to meeting nitrogen needs, the administration rate is governed, especially during the first few days of therapy, by the patient's tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations 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. 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. Sudden cessation in administration of a concentrated dextrose solution may result in insulin reaction due to high levels of endogenous insulin. Such solutions should be withdrawn slowly. Peripheral Vein Administration: In patients requiring parenteral nutrition for whom the central vein route is not indicated, this injection can be mixed with low concentration dextrose solutions and administered by peripheral vein with or without fat emulsion. Intravenous fat emulsion provides approximately 1.1 kcal/mL (10%) or 2.0 kcal/mL (20%) and may be administered along with amino acid-dextrose solutions by means of a short Y-connector near the infusion site to supplement caloric intake. Fat, however, should not be the sole caloric intake since studies have indicated that glucose is more nitrogen sparing in the stressed patient. Protein-Sparing: For well nourished patients who require short-term parenteral support, this injection can be administered peripherally with or without carbohydrate calories. Such infusates can be prepared by dilution of this injection with 5% Dextrose Injection and/or Sterile Water for Injection to prepare solutions which may be administered by peripheral vein, not to exceed twice normal serum osmolarity. Depending upon the clinical condition of the patient, approximately 3 liters of solution may be administered per 24 hour period. When used postoperatively, the therapy should begin with 1000 mL the first postoperative day. Thereafter, the dose may be increased to 3000 mL per day. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Use of a final filter is recommended during administration of all parenteral solutions where possible. Filters of less than 1.2 microns pore size must not be used with admixtures containing fat emulsions. A slight yellow color does not alter the quality and efficacy of the product. Do not use unless solution is clear and seal is intact. 20% PROSOL - sulfite-free (Amino Acid) Injection in the Pharmacy Bulk Package is intended for use in the preparation of sterile, intravenous admixtures. Additives may be incompatible with the fluid withdrawn from this container. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store any unused portion of 20% PROSOL - sulfite-free (Amino Acid) Injection. Any storage of admixtures should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.

DESCRIPTION SECTION.


DESCRIPTION 20% PROSOL - sulfite-free (Amino Acid) Injection is a sterile, nonpyrogenic, hypertonic solution of essential and nonessential amino acids provided in a Pharmacy Bulk Package. A Pharmacy Bulk Package is a container of a sterile preparation for parenteral use that contains many single doses. The contents are intended for use in a pharmacy admixture program and are restricted to the preparation of admixtures for intravenous infusion. The VIAFLEX Plastic Container is fabricated from a specially formulated polyvinyl chloride (PL 146 Plastic). 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), up to 5 parts 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. Each 100 mL of 20% PROSOL - sulfite-free (Amino Acid) Injection contains: Amino Acids 20.0 g Total Nitrogen 3.21 g pH 6.0 (5.5 to 6.5) (pH adjusted with glacial acetic acid.) Essential Amino Acids Valine - (CH3)2 CHCH (NH2) COOH 1.44 g Lysine (added as Lysine Acetate) - H2N (CH2)4 CH (NH2) COOH 1.35 g Histidine - (C3H3N2) CH2CH (NH2) COOH 1.18 g Isoleucine - CH3CH2CH (CH3) CH (NH2) COOH 1.08 g Leucine - (CH3)2 CHCH2CH (NH2) COOH 1.08 g Phenylalanine - (C6H5) CH2 CH (NH2) COOH 1.00 g Threonine - CH3CH (OH) CH (NH2) COOH 980 mg Methionine - CH3S (CH2)2 CH (NH2) COOH 760 mg Tryptophan - (C8H6N) CH2CH (NH2) COOH 320 mg Nonessential Amino Acids Alanine - CH3CH (NH2) COOH 2.76 g Glycine - H2NCH2COOH 2.06 g Arginine - H2NC (NH) NH (CH2)3 CH (NH2) COOH 1.96 g Proline - [(CH2)3NHCH] COOH 1.34 g Glutamic Acid - HOOC (CH2)2 CH (NH2) COOH 1.02 g Serine - HOCH2 CH (NH2) COOH 1.02 g Aspartic Acid - HOOC CH2 CH (NH2) COOH 600 mg Tyrosine - [C6H4 (OH)] CH2CH (NH2) COOH 50 mg Anion profiles per liter Balanced by ions from amino acids. Acetate from Lysine Acetate and glacial acetic acid 140 mEq 140 mEq Osmolarity (calc.) 1835 mOsmol/L

OVERDOSAGE SECTION.


OVERDOSAGE In the event of overhydration or solute overload, re-evaluate the patient and institute appropriate corrective measures. See CONTRAINDICATIONS and WARNINGS.

PRECAUTIONS SECTION.


PRECAUTIONS 20% PROSOL - sulfite-free (Amino Acid) Injection is a highly concentrated amino acid solution used for the preparation of sterile total parenteral nutrition admixtures (see DOSAGE AND ADMINISTRATION). Some of the amino acids in 20% PROSOL - sulfite-free (Amino Acid) Injection are close to their limit of solubility, and, as such, a small number of amino acid crystals may form upon storage. If amino acid crystals are present, they will re-dissolve upon dilution during admixture compounding. Do not use unless admixture is free of visible particulate. Use of a final filter is recommended during administration of all parenteral solutions where possible. It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis. Concentrated dextrose solutions are an effective source of such calories. With the administration of 20% PROSOL - sulfite-free (Amino Acid) Injection in combination with highly concentrated dextrose solutions, hyperglycemia, glycosuria and hyperosmolar syndrome may result. Blood and urine glucose should be monitored on a routine basis in patients receiving this therapy. Sudden cessation in administration of a concentrated dextrose solution may result in insulin reaction due to high levels of endogenous insulin. Parenteral nutrition mixtures should be withdrawn slowly. The metabolizable acetate anion and amino acid profile in this injection were designed to minimize or prevent occurrences of hyperchloremic metabolic acidosis and hyperammonemia. However, the physician should be aware of appropriate countermeasures if they become necessary. Strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava. Because of its antianabolic activity, concurrent administration of tetracycline may reduce the protein-sparing effect of infused amino acids. Care should be taken to avoid excess fluid accumulation, particularly in patients with renal disease, pulmonary insufficiency and heart disease. During protein-sparing therapy in the absence of supporting carbohydrate metabolism, an accumulation of ketone bodies in the blood often occurs. Correction of ketonemia usually can be accomplished by administering some carbohydrates. Protein-sparing therapy is useful for periods up to 10 to 12 days. Patients requiring nutritional support thereafter should be placed on oral or parenteral regimens that employ adequate nonprotein calorie components. 20% PROSOL - sulfite-free (Amino Acid) Injection is not intended for direct infusion, and, as such, should never be administered undiluted. Drug product contains no more than 25 g/L of aluminum. Laboratory Tests Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring during administration. Laboratory tests should include blood glucose, serum electrolytes, liver and kidney function, serum osmolarity, blood ammonia, serum protein, pH, hematocrit, WBC and urinary glucose. When 20% PROSOL - sulfite-free (Amino Acid) Injection is combined with electrolytes, care should be used in administering this solution to patients with congestive heart failure, renal failure, edema, adrenal hyperactivity, acid base imbalance and those receiving diuretics or antihypertensive therapy. Serum electrolytes should be monitored daily. When 20% PROSOL - sulfite-free (Amino Acid) Injection is infused without adequate non-protein calories, monitoring of BUN is required. Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies with 20% PROSOL - sulfite-free (Amino Acid) Injection have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility. Pregnancy: Teratogenic Effects Pregnancy Category C. Animal reproduction studies have not been conducted with 20% PROSOL - sulfite-free (Amino Acid) Injection. It is also not known whether 20% PROSOL - sulfite-free (Amino Acid) Injection can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. 20% PROSOL - sulfite-free (Amino Acid) Injection should be given to a pregnant woman only if clearly needed. Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for adverse reactions, e.g., hyperammonemia in nursing infants, caution should be exercised when 20% PROSOL - sulfite-free (Amino Acid) Injection is administered to a nursing mother. Pediatric Use: Safety and effectiveness of 20% PROSOL - sulfite-free (Amino Acid) Injection have not been established by adequate and well-controlled studies in pediatric patients. Geriatric Use: Clinical studies of 20% PROSOL - sulfite-free (Amino Acid) Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from other younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY 20% PROSOL - sulfite-free (Amino Acid) Injection administered via central vein, after appropriate dilution, will provide biologically utilizable source material for protein synthesis when used with concentrated calorie sources (such as hypertonic dextrose and/or fat emulsion), electrolytes, vitamins and minerals. Administered peripherally after appropriate dilution or with minimal calorie supplementation (such as 5% dextrose), it enhances the conservation of body protein.

CONTRAINDICATIONS SECTION.


CONTRAINDICATIONS Hypersensitivity to one or more amino acids Severe liver disease or hepatic coma Anuria

WARNINGS SECTION.


WARNINGS This injection is for compounding only, not for direct infusion. Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store. Because of the potential for life-threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrient admixture. Caution should be exercised when admixing 20% PROSOL - sulfite-free (Amino Acid) Injection. This solution should be used promptly after admixing. Any storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours. Reference should be made to I.V. Fat Emulsion package insert and high concentration dextrose injection from Baxter Healthcare Corporation package insert for detailed information on each component. Proper administration of this injection requires a knowledge of fluid and electrolyte balance and nutrition as well as clinical expertise in recognition and treatment of the complications which may occur. Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino acid imbalances, hyperammonemia, stupor and coma. Hyperammonemia is of special significance in infants. This reaction appears to be related to a deficiency of the urea cycle amino acids of genetic or product origin. It is essential that blood ammonia be measured frequently in infants. Conservative doses of this injection should be given to patients with known or suspected hepatic dysfunction. Should symptoms of hyperammonemia develop, administration should be discontinued and the patient's clinical status reevaluated. Administration of amino acid solutions in the presence of impaired renal function presents special issues associated with retention of electrolytes. This injection should not be administered simultaneously with blood through the same infusion set because of the possibility of pseudoagglutination. 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 g/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration. Administration by central venous catheter should be used only by those familiar with this technique and its complications.