TROPHAMINE

TrophAmine® (10% Amino Acid Injection) is a sterile, nonpyrogenic, hypertonic solution containing crystalline amino acids. 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 10% Isoleucine USP 0.82 g Leucine USP 1.4 g Lysine 0.82 g (added as Lysine Acetate USP 1.2 g) Methionine USP 0.34 g Phenylalanine USP 0.48 g Threonine USP 0.42 g Tryptophan USP 0.2 g Valine USP 0.78 g Cysteine <0.016 g (as Cysteine HCl∙H 2 O USP <0.024 g) Histidine USP Holt LE, Snyderman SE: The amino acid requirements of infants. JAMA 1961; 175(2):124–127. 0.48 g Tyrosine 0.24 g (added as Tyrosine USP 0.044 g and N-Acetyl-L-Tyrosine 0.24 g) Nonessential Amino Acids Alanine USP 0.54 g Arginine USP 1.2 g Proline USP 0.68 g Serine USP 0.38 g Glycine USP 0.36 g L-Aspartic Acid 0.32 g L-Glutamic Acid 0.5 g Taurine Rigo J, Senterre J: Is taurine essential for the neonates? Biol Neonate 1977; 32:73–76. Gaull G, Sturman JA, Räihä NCR: Development of mammalian sulfur metabolism: Absence of cystothionase in human fetal tissues. Pediatr Res 1972; 6:538–547. 0.025 g Water for Injection USP qs pH adjusted with Glacial Acetic Acid USP pH: 5.5 (5.0–6.0) Calc. Osmolarity (mOsmol/liter) 866 Total Amino Acids (grams/liter) 100 Total Nitrogen (grams/liter) 15.5 Protein Equivalent (grams/liter) 97 Electrolytes (mEq/liter) Provided as acetic acid and lysine acetate. Acetate (CH 3 COO – ) 96.2 Chloride <3

TrophAmine® is indicated for the nutritional support of infants (including those of low birth weight) and young pediatric patients requiring TPN via either central or peripheral infusion routes. Parenteral nutrition with TrophAmine® is indicated to prevent nitrogen and weight loss or treat negative nitrogen balance in infants and young 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 non-protein 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 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 5-10% 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).

The objective of nutritional management of infants and young pediatric patients is the provision of sufficient amino acid and caloric support for protein synthesis and growth. The total daily dose of TrophAmine® (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. Dosage should also be guided by the patient’s fluid intake limits and glucose and nitrogen tolerances, as well as by metabolic and clinical response. Recommendations for allowances of protein in infant nutrition have ranged from 2 to 4 grams of protein per kilogram of body weight per day (2 to 4 g/kg/day). Suskind RM: Textbook of Pediatric Nutrition, Raven Press, New York, 1981. The recommended dosage of TrophAmine® is 2 to 2.5 grams of amino acids per kilogram of body weight per day (2 to 2.5 g/kg/day) for infants up to 10 kilograms. For infants and young pediatric patients larger than 10 kilograms, the total dosage of amino acids should include the 20 to 25 grams/day for the first 10 kg of body weight plus 1 to 1.25 g/day for each kg of body weight over 10 kilograms. Typically, TrophAmine® is admixed with 50% or 70% Dextrose Injection USP supplemented with electrolytes and vitamins and administered over a period of time not to exceed 24 hours. Total daily fluid intake should be appropriate for the patient’s age and size. A fluid dose of 125 mL per kilogram body weight per day is appropriate for most infants on TPN. Although nitrogen requirements may be higher in severely hypercatabolic or depleted patients, provision of additional nitrogen may not be possible due to fluid intake limits, nitrogen, or glucose intolerance. Cysteine is considered to be an essential amino acid in infants and young pediatric patients. An admixture of cysteine hydrochloride to the TPN solution is therefore recommended. Based on clinical studies, the recommended dosage is 1 mmole of L-cysteine hydrochloride monohydrate per kilogram of body weight per day. 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. 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. The provision of sufficient intracellular electrolytes, principally potassium, magnesium, and phosphate, is required for optimum utilization of amino acids. 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 salts to provide bicarbonate precursor. The electrolyte content of TrophAmine® must be considered when calculating daily electrolyte intake. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently. Appropriate vitamins, minerals and trace elements should also be provided. 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. Use of an infusion pump is advisable to maintain a steady infusion rate during central venous infusion. Peripheral Parenteral Nutrition. For patients in whom the central venous route is not indicated and who can consume adequate calories enterally, TrophAmine® (Amino Acid Injection) may be administered by peripheral vein with or without parenteral carbohydrate calories. Such infusates can be prepared by dilution with B. Braun’s Sterile Water for Injection or 5%-10% Dextrose Injection to prepare isotonic or slightly hypertonic solutions for peripheral infusion. It is essential that peripheral infusion be accompanied by adequate caloric intake. In pediatric patients, the final solution should not exceed twice normal serum osmolarity (718 mOsmol/L). Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. TrophAmine® may be admixed with solutions which contain phosphate or which have been supplemented with phosphate. The presence of calcium and magnesium ions in an additive solution should be considered when phosphate is also present, in order to avoid precipitation. Care must be taken to avoid incompatible admixtures. Consult with pharmacist.

TrophAmine® 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.

See “ WARNINGS ” and “ Special Precautions for Central Venous Nutrition . ” Reactions reported in clinical studies as a result of infusion of the parenteral fluid were water weight gain, edema, increase in BUN, and mild acidosis. 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 reaction at 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. 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. 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. 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.

Some additives may be incompatible. Consult with pharmacist. When introducing additives, use aseptic techniques. Mix thoroughly. Do not store.

Storage Store in the closed corrugated case; do not expose TrophAmine® and/or TrophAmine®-containing admixed parenteral nutrition (PN) solution to light. Do not remove container from overwrap until ready to use. Do not use if overwrap has been opened or damaged. Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Solution that has been frozen must not be used.