Isoleucine, Leucine, Lysine Acetate, Methionine, Phenylalanine, Threonine, Tryptophan, Valine, Alanine, Arginine, Aspartic Acid, Glutamic Acid, Histidine, Proline, Serine, N-Acetyltyrosine, And Glycine

INDICATIONS AND USAGE Aminosyn II, Sulfite-Free, (an amino acid injection) infused with dextrose by peripheral vein infusion is indicated as a source of nitrogen in the nutritional support of patients with adequate stores of body fat, in whom, for short periods of time, oral nutrition cannot be tolerated, is undesirable, or inadequate. SUPPLEMENTAL ELECTROLYTES, IN ACCORDANCE WITH THE PRESCRIPTION OF THE ATTENDING PHYSICIAN, MUST BE ADDED TO AMINOSYN II SOLUTIONS WITHOUT ELECTROLYTES. Aminosyn II can be administered peripherally with dilute (5 to 10%) dextrose solution and I.V. fat emulsion as a source of nutritional support. This form of nutritional support can help to preserve protein and reduce catabolism in stress conditions where oral intake is inadequate. Aminosyn II is also indicated for central vein infusion to prevent or reverse negative nitrogen balance in patients where the alimentary tract, by the oral, gastrostomy or jejunostomy route cannot or should not be used and gastrointestinal absorption of protein is impaired.

DOSAGE AND ADMINISTRATION Each 100 mL of Aminosyn II contains: Amino Acids Nitrogen Aminosyn II 10% 10 g 1.53 g Aminosyn II 15% 15 g 2.30 g The total daily dose of the solution depends on the daily protein requirements and on the patient’s metabolic and clinical response. 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. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. COLOR VARIATION FROM PALE YELLOW TO YELLOW IS NORMAL AND DOES NOT ALTER EFFICACY. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Aminosyn II in the 2000 mL flexible Pharmacy Bulk Package is designed for use with manual, gravity flow operations and automated gravimetric compounding devices for preparing intravenous nutritional admixtures. Admixtures must be stored under refrigeration and used within 24 hours of admixing. Peripheral Vein Nutritional Maintenance A mixture of Aminosyn II and dextrose diluted to a final concentration of 5% to 10% amino acids and 5% to 10% dextrose is suitable for administration by peripheral vein. This solution is not intended for central vein administration because it does not contain adequate amounts of amino acids or electrolytes. For peripheral intravenous infusion, 1 to 1.5 g/kg/day of total amino acids will reduce protein catabolism. Infusion or ingestion of carbohydrate or lipid will not reduce the nitrogen sparing effect of intravenous amino acid infusions at this dose. As with all intravenous fluid therapy, the primary aim is to provide sufficient water to compensate for insensible, urinary and other (nasogastric suction, fistula drainage, diarrhea) fluid losses. Total fluid requirements, as well as electrolyte and acid-base needs, should be estimated and appropriately administered. For an amino acid solution of specified total concentration, the volume required to meet amino acid requirements per 24 hours can be calculated. After making an estimate of the total daily fluid (water) requirement, the balance of fluid needed beyond the volume of amino acid solution required can be provided either as a noncarbohydrate or a carbohydrate-containing electrolyte solution. I.V. lipid emulsion may be substituted for part of the carbohydrate-containing solution. Vitamins and additional electrolytes as needed for maintenance or to correct imbalances may be added to the amino acid solution. If desired, only one-half of an estimated daily amino acid requirement of 1.5 g/kg can be given on the first day. Amino acids together with dextrose in concentrations of 5% to 10% infused into a peripheral vein can be continued while oral nutrition is impaired. However, if a patient is unable to take oral nourishment for a prolonged period of time, institution of total parenteral nutrition with exogenous calories should be considered. Central Vein Total Parenteral Nutrition For central vein infusion with concentrated dextrose solution, alone or with I.V. lipid, the total daily dose of the amino acid solution depends upon daily protein requirements and 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. ADULTS Solutions containing 3.5 to 5% amino acids with 5 to 10% glucose may be infused with a fat emulsion by peripheral vein to provide approximately 1400 to 2000 kcal/day. Fat emulsion administration should be considered when prolonged 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. Aminosyn II solution should only be infused via a central vein when admixed with sufficient dextrose to provide full caloric requirements in patients who require prolonged total parenteral nutrition. I.V. lipid may be administered to provide part of the calories, if desired. Serum lipids should be monitored for evidence of essential fatty acid deficiency in patients maintained on fat-free TPN. Total parenteral nutrition (TPN) may be started with 10% dextrose added to the calculated daily requirement of amino acids (1.5 g/kg for a metabolically stable patient). Dextrose content is gradually increased over the next few days to the estimated daily caloric need as the patient adapts to the increasing amounts of dextrose. Each gram of dextrose provides approximately 3.4 kcal. Each gram of fat provides 9 kcal. The average depleted major surgical patient with complications requires between 2500 and 4000 kcal and between 12 and 24 grams of nitrogen per day. An adult patient in an acceptable weight range with restricted activity who is not hypermetabolic, requires about 30 kcal/kg of body weight/day. Average daily adult fluid requirements are between 2500 and 3000 mL and may be much higher with losses from fistula drainage or severe burns. Typically, a hospitalized patient may lose 12 to 18 grams of nitrogen a day, and in severe trauma the daily loss may be 20 to 25 grams or more. Aminosyn II solutions without electrolytes are intended for patients requiring individualized electrolyte therapy. Sodium, chloride, potassium, phosphate, calcium and magnesium are major electrolytes which should be added to Aminosyn II as required. SERUM ELECTROLYTES SHOULD BE MONITORED AS INDICATED. Electrolytes may be added to the nutrient solution as indicated by the patient’s clinical condition and laboratory determinations of plasma values. Major electrolytes are sodium, chloride, potassium, phosphate, magnesium and calcium. Vitamins, including folic acid and vitamin K, are required additives. The trace element supplements should be given when long-term parenteral nutrition is undertaken. Iron is added to the solution or given intramuscularly in depot form as indicated. Vitamin B 12 , vitamin K and folic acid are given intramuscularly or added to the solution as desired. Calcium and phosphorus additives are potentially incompatible when added to the TPN admixture. In patients with hyperchloremic or other metabolic acidosis, sodium and potassium may be added as the acetate or lactate salts to provide bicarbonate alternates. In adults, hypertonic mixtures of amino acids and dextrose may be safely administered by continuous infusion through a central venous catheter with the tip located in the vena cava. Typically, each liter of central vein TPN solution for adults contains 42.5 to 50 g of Aminosyn II with approximately 250 ± 100 g of dextrose; supplementary nonprotein calories from intravenous fat emulsion may be prescribed, at the discretion of the physician. The rate of intravenous infusion initially should be 2 mL/min and may be increased gradually. If administration should fall behind schedule, no attempt to “catch up” to planned intake should be made. In addition to meeting protein needs, the rate of administration is governed by the patient’s glucose tolerance estimated by glucose levels in blood and urine. Aminosyn II solution, when mixed with an appropriate volume of concentrated dextrose, offers a higher concentration of calories and nitrogen per unit volume. This solution is indicated for patients requiring larger amounts of nitrogen than could otherwise be provided or where total fluid load must be kept to a minimum, for example, patients with renal failure. Provision of adequate calories in the form of hypertonic dextrose may require exogenous insulin to prevent hyperglycemia and glycosuria. To prevent rebound hypoglycemia, do not abruptly discontinue administration of nutritional solutions. PEDIATRIC Pediatric requirements for parenteral nutrition are constrained by the greater relative fluid requirements of the infant and greater caloric requirements per kilogram. Amino acids are probably best administered in a 2.5% concentration. For most pediatric patients on intravenous nutrition, 2.5 grams amino acids/kg/day with dextrose alone or with I.V. lipid calories of 100 to 130 kcal/kg/day is recommended. In cases of malnutrition or stress, these requirements may be increased. It is acceptable in pediatrics to start with a nutritional solution of half strength at a rate of about 60 to 70 mL/kg/day. Within 24 to 48 hours the volume and concentration of the solution can be increased until the full strength pediatric solution (amino acids and dextrose) is given at a rate of 125 to 150 mL/kg/day. Supplemental electrolytes and vitamin additives should be administered as deemed necessary by careful monitoring of blood chemistries and nutritional status. Addition of iron is more critical in the infant than the adult because of the increasing red cell mass required for the growing infant. Serum lipids should be monitored for evidence of essential fatty acid deficiency in patients maintained on fat-free TPN. Bicarbonate should not be administered during infusion of the nutritional solution unless deemed absolutely necessary. To ensure the precise delivery of the small volumes of fluid necessary for total parenteral nutrition in infants, accurately calibrated and reliable infusion systems should be used. A basic solution for pediatric use should contain 25 grams of amino acids and 200 to 250 grams of glucose per 1000 mL, administered from containers containing 250 or 500 mL. Such a solution given at the rate of 145 mL/kg/day provides 130 kcal/kg/day. Recommended Directions for Use of the Pharmacy Bulk Package Use Aseptic Technique During use, container must be stored, and all manipulations performed, in an appropriate laminar flow hood. Remove cover from outlet port at bottom of container. Insert piercing pin of sterile transfer set and suspend unit in a laminar flow hood. Insertion of a piercing pin into the outlet port should be performed only once in a Pharmacy Bulk Package solution. Once the outlet site has been entered, the withdrawal of container contents should be completed promptly in one continuous operation. Should this not be possible, a maximum time of 4 hours from transfer set pin or implement insertion is permitted to complete fluid transfer operations; i.e., discard container no later than 4 hours after initial closure puncture. Sequentially dispense aliquots of Aminosyn II into I.V. containers using appropriate transfer set. During fluid transfer operations, the Pharmacy Bulk Package should be maintained under the storage conditions recommended in the labeling. Additives may be incompatible with fluid withdrawn from this container. Consult with pharmacist, if available. When compounding admixtures, use aseptic technique. Mix thoroughly. Do not store solutions containing additives. Because of the potential for life-threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrient mixture. WARNING: Do not use flexible container in series connections.

ADVERSE REACTIONS Peripheral Infusions A 3.5% to 5% solution of amino acids (without additives) is slightly hypertonic. Use of large peripheral veins, inline filters, and slowing the rate of infusion may reduce the incidence of local venous irritation. Electrolyte additives should be spread throughout the day. Irritating additive medications may need to be infused at another venous site. Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino acid solutions.