Lysine Acetate, Leucine, Phenylalanine, Valine, Isoleucine, Methionine, Threonine, Tryptophan, Alanine, Arginine, Glycine, Histidine, Proline, Glutamic Acid, Serine, Aspartic Acid, and Tyrosine

Plenamine™ 15% is indicated as an amino acid (nitrogen) source in parenteral nutrition regimens. This use is appropriate when the enteral route is inadvisable, inadequate or not possible, as when: — Gastrointestinal absorption is impaired by obstruction, inflammatory disease or its complications, or antineoplastic therapy; — Bowel rest is needed because of gastrointestinal surgery or its complications such as ileus, fistulae or anastomotic leaks; — Tube feeding methods alone cannot provide adequate nutrition.

This solution should not be used in patients in hepatic coma, severe renal failure, metabolic disorders involving impaired nitrogen utilization or hypersensitivity to one or more amino acids.

Administration of amino acids solutions at excessive rates or to patients with hepatic insufficiency may result in plasma amino acid imbalances, hyperammonemia, prerenal azotemia, stupor and coma. Conservative doses of amino acids should be given to these patients, 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 re-evaluated. 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.

A. General 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. The administration of Plenamine™ 15% Amino Acids Injection as part of total parenteral nutrition (TPN) with large volumes of hyperosmotic fluids requires periodic monitoring of the patient for signs of hyperosmolarity, hyperglycemia, glycosuria and hypertriglyceridemia. During parenteral nutrition with concentrated dextrose and amino acids solutions, essential fatty acid deficiency syndrome may develop but may not be clinically apparent. Early demonstration of this condition can only be accomplished by gas liquid chromatographic analysis of plasma lipids. The syndrome may be prevented or corrected by appropriate treatment with intravenous fat emulsions. For complete nutritional support, TPN regimens must also include multiple vitamins and trace elements. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. Although the metabolizable acetate ion in Plenamine™ 15% diminishes the risk of acidosis, the physician must be alert to the potential appearance of this disorder. Initiation and termination of infusions of TPN fluids must be gradual to permit adjustment of endogenous insulin release. Undiluted Plenamine™ 15% should not be administered peripherally. When administered centrally, it should be diluted with appropriate diluents, e.g., dextrose, electrolytes and other nutrient components, to at least half strength. (See DOSAGE AND ADMINISTRATION . ) Caution against volume overload should be exercised. Drug product contains no more than 25 mcg/L of aluminum. B. Laboratory Tests Infusion of Plenamine™ 15% without concomitant infusion of an adequate number of non-protein calories may result in elevated BUN. Monitoring of BUN is required and the balance between Plenamine™ 15% and the calorie source may require adjustment. Frequent clinical evaluations and laboratory determinations are required to prevent the complications which may occur during the administration of solutions used in TPN. 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 Plenamine™ 15% 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. Total volume infused should be closely monitored. Serum electrolytes should be monitored daily in these patients. C. Carcinogenesis, Mutagenesis, Impairment of Fertility Studies with Plenamine™ 15% have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility. D. Pregnancy Category C Animal reproduction studies have not been conducted with Plenamine™ 15%. It is also not known whether Plenamine™ 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Plenamine™ 15% should be given to a pregnant woman only if clearly needed. E. Nursing Mothers Caution should be exercised when Plenamine™ 15% is administered to a nursing woman. F. Pediatric Use Safety and effectiveness of Plenamine™ 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature. G. Special Precautions for Central Infusion TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions. H. Admixtures Admixtures should be prepared under a laminar flow hood using aseptic technique. Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator. Filters of less than 1.2 micron pore size must not be used with admixtures containing lipid emulsion. I. Use only if bag and seal are undamaged and solution is clear. IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL, BASED ON CURRENT MEDICAL PRACTICES, BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

(See WARNINGS , PRECAUTIONS and Special Precautions for Central Infusion .)

D. Pregnancy Category C Animal reproduction studies have not been conducted with Plenamine™ 15%. It is also not known whether Plenamine™ 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Plenamine™ 15% should be given to a pregnant woman only if clearly needed.

E. Nursing Mothers Caution should be exercised when Plenamine™ 15% is administered to a nursing woman.

G. Special Precautions for Central Infusion TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions.

F. Pediatric Use Safety and effectiveness of Plenamine™ 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature.

H. Admixtures Admixtures should be prepared under a laminar flow hood using aseptic technique. Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator. Filters of less than 1.2 micron pore size must not be used with admixtures containing lipid emulsion.