AMINOSYN-PF

Aminosyn ® -PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) is a sterile, nonpyrogenic solution for intravenous infusion. Aminosyn-PF 10% is oxygen sensitive. The Pharmacy Bulk Package is a sterile dosage form which contains multiple single doses for use only in a pharmacy bulk admixture program. The formulation is described below: Aminosyn-PF 10% An Amino Acid Injection — Pediatric Formula Essential Amino Acids (mg/100 mL) Isoleucine 760 Leucine 1200 Lysine (acetate)* 677 Methionine 180 Phenylalanine 427 Threonine 512 Tryptophan 180 Valine 673 * Amount cited is for lysine alone and does not include the acetate salt. Nonessential Amino Acids (mg/100 mL) Alanine 698 Arginine 1227 Aspartic Acid 527 Glutamic Acid 820 Glycine 385 Histidine 312 Proline 812 Serine 495 Taurine 70 Tyrosine 44 Electrolytes (mEq/L) Sodium (Na + ) None Potassium (K + ) None Chloride (Cl − ) None Acetate (C 2 H 3 O 2 − ) a 46 Product Characteristics Protein Equivalent (Approx. grams/L) 100 Total Nitrogen (grams/L) 15.2 Osmolarity (mOsmol/L) 788 pH (range) 5.5 (5.0 to 6.5) Specific Gravity 1.03 a From lysine acetate. The formulas for the individual amino acids present in Aminosyn-PF 10% are as follows: Essential Amino Acids Isoleucine CH 3 CH 2 CH(CH 3 )CH(NH 2 )COOH Leucine (CH 3 ) 2 CHCH 2 CH(NH 2 )COOH Lysine Acetate H 2 N(CH 2 ) 4 CH(NH 2 )COOH • CH 3 COOH Methionine CH 3 S(CH 2 ) 2 CH(NH 2 )COOH Phenylalanine Threonine CH 3 CH(OH)CH(NH 2 )COOH Tryptophan Valine (CH 3 ) 2 CHCH(NH 2 )COOH Nonessential Amino Acids Alanine CH 3 CH(NH 2 )COOH Arginine H 2 NC(NH)NH(CH 2 ) 3 CH(NH 2 )COOH L-Aspartic Acid HOOCCH 2 CH(NH 2 )COOH L-Glutamic Acid HOOC(CH 2 ) 2 CH(NH 2 )COOH Glycine H 2 NCH 2 COOH Histidine Proline Serine HOCH 2 CH(NH 2 )COOH Taurine H 2 N − CH 2 CH 2 − SO 3 H Tyrosine The flexible plastic container is fabricated from a specially formulated polyvinylchloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. 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 Pharmacy Bulk Package is designed for use with manual, gravity flow operations and automated compounding devices for preparing sterile parenteral nutrient admixtures; it contains no bacteriostat. Multiple single doses may be dispensed during continual aliquoting operations. Withdrawal of container contents should be promptly completed within 4 hours after initial closure puncture. structural Phenylalanine structural formula Tryptophan structural formula Histidine structural formula Proline structural formula Tyrosine

Aminosyn-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) is indicated for the nutritional support of infants (including those of low birth weight) and young children requiring TPN via either central or peripheral infusion routes. Parenteral nutrition with Aminosyn-PF 10% is indicated to prevent nitrogen and weight loss or treat negative nitrogen balance in infants and young children 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 non-protein calories are dependent on various factors, such as nutritional and metabolic status of the patient, anticipated duration of parenteral nutrition support, and vein tolerance. See DOSAGE AND ADMINISTRATION for additional information. Central Venous Infusion 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 infants 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 to 10% dextrose solutions may be infused by peripheral vein, supplemented, if desired, with fat emulsion.

Aminosyn-PF 10%, Sulfite-Free, is an amino acid injection-pediatric formula not intended for direct infusion. Admixtures should be made by or under the direction of a pharmacist using strict aseptic technique under a laminar flow hood. Admixtures must be stored under refrigeration and used within 24 hours of admixing. The total daily dose of the solution depends on the daily protein requirements and on the patient’s metabolic and clinical response. Pediatric requirements for parenteral nutrition are constrained by the greater relative fluid requirements of the infant and greater caloric requirements per kilogram than in the adult. The recommended intravenous dose of Aminosyn-PF 10% is up to 2.5 g amino acid/kg/day for infants up to 10 kg. For infants and children larger than 10 kg, the total daily dose of amino acids should be up to 25 g amino acids/day for the first 10 kg of body weight plus 1.0 to 1.25 g amino acid for each kg of body weight over 10 kg. Initial amino acid dosage levels of 1.0 g/kg/day may be increased gradually in increments of 0.5 g/kg/day to approximate desired intake levels. Aminosyn-PF 10% should be diluted with dextrose prior to use. Nonprotein calories should constitute approximately 100 to 130 kcal/kg/day. Part of the nonprotein caloric requirement may be provided as lipid emulsion administered concurrently to provide up to 60% of daily calories at a dose not to exceed 4 g fat/kg/day. Fluid intake for the infant receiving central venous TPN should be approximately 125 mL/kg/day (range: 100 to 175 mL/kg/day), depending on the clinical condition of the patient. Fat emulsion coadministration should be considered when prolonged (more than 5 days) parenteral nutrition 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 TPN. Premature infants with respiratory distress syndrome suspected of having a patent ductus arteriosus should be given fluids more cautiously. Cysteine is considered to be an essential amino acid for infants, especially preterm infants with potentially immature enzyme pathways. Therefore, addition of a cysteine supplement to the TPN admixture is recommended. The intake of cysteine by the preterm infant ingesting maternal milk is approximately 78 mg/kg/day. The suggested intravenous dosage level for Cysteine Hydrochloride Injection, USP is 500 mg (10 mL) for every 12.5 g (125 mL) of Aminosyn-PF 10% administered (see package insert for Cysteine Hydrochloride Injection, USP). In order to avoid potential insolubility of cysteine hydrochloride in admixtures, the foregoing concentration should not be exceeded. 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 solutions are abruptly discontinued. SERUM ELECTROLYTES SHOULD BE MONITORED FREQUENTLY. 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. Daily administration of intravenous vitamin supplements including a complete complement of fat and water-soluble vitamins is required. Trace metal additives including zinc, copper, manganese, and chromium should also be provided, especially when long-term parenteral therapy is anticipated. Calcium and phosphorus are added to the solution as indicated. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. In patients with hyperchloremic or other metabolic acidosis, sodium and potassium may be added as the acetate or lactate salts to provide bicarbonate alternates. Bicarbonate should not be administered during infusion of the nutritional solution unless deemed absolutely necessary. Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store. 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. Central Venous Nutrition 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 superior vena cava. Initial infusion rates should be slow, and gradually increased to the recommended 60-125 mL per kilogram body weight per day. 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 rate of administration, particularly during the first few days of therapy, is governed 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 determinations of glucose levels in blood and urine. Peripheral Parenteral Nutrition For patients in whom the central venous route is not indicated and who can consume adequate calories enterally, Aminosyn-PF 10% may be administered by peripheral vein with parenteral nonprotein calories. The concentration of dextrose in the final admixture is 5 to 10%, and simultaneous administration of lipid emulsion is recommended both as a calorie source and to attenuate the potentially irritating effects of the hypertonic nutritional admixture. Fat emulsion may comprise up to 60% of the daily caloric intake at a dosage level not to exceed 4 g fat/kg/day. It is essential that peripheral infusion be accompanied by adequate caloric intake. 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. 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-PF 10% 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.

Aminosyn-PF 10%, Sulfite-Free, (an amino acid injection — pediatric formula) is contraindicated in patients with untreated anuria, hepatic coma, inborn errors of amino acid metabolism (including those involving branched chain amino acid metabolism such as maple syrup urine disease and isovaleric acidemia), or hypersensitivity to one or more amino acids present in the solution.

Local reactions consisting of erythema, phlebitis and thrombosis at the infusion site have occurred with peripheral intravenous infusion of amino acids particularly if other substances, such as antibiotics, are also administered through the same site. In such cases the infusion site should be changed promptly to another vein. 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 injected at another venous site. Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino acid solutions. 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.