Rx only

DESCRIPTION

Aminosyn® (a crystalline amino acid solution) is a sterile, nonpyrogenic solution for intravenous infusion. Five different formulations are available:

* Amount cited is for Lysine alone and does not include the acetate salt.

a Includes 7 mEq Na+/liter from the antioxidant, sodium hydrosulfite.

b Includes 5.4 mEq K+/liter from the antioxidant, potassium metabisulfite.

c Includes chloride from HCl added for processing and pH adjustment.

d Includes acetate from acetic acid used in processing and from Lysine acetate.

e Adjusted with acetic acid.

f Adjusted with acetic acid and hydrochloric acid.

The formulations contain the following added ingredients/100 mL:

Aminosyn 5%, 7%, 8.5% and 10%

Potassium metabisulfite added, 60 mg.

Aminosyn 3.5%

Sodium hydrosulfite added, 60 mg.

The formulas for the individual amino acids present in Aminosyn (a crystalline amino acid solution) are as follows:

CLINICAL PHARMACOLOGY

Aminosyn provides crystalline amino acids to promote protein synthesis and wound healing, and to reduce the rate of endogenous protein catabolism. Aminosyn, given by central venous infusion in combination with concentrated dextrose, electrolytes, vitamins, trace metals, and ancillary fat supplements, constitutes total parenteral nutrition (TPN). Aminosyn can also be administered by peripheral vein with dextrose and maintenance electrolytes. Intravenous fat emulsion may be substituted for part of the carbohydrate calories during either TPN or peripheral vein administration of Aminosyn.

INDICATIONS AND USAGE

Aminosyn 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 SOLUTIONS WITHOUT ELECTROLYTES.

Aminosyn 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.

When administered with concentrated dextrose solutions with or without fat emulsions, Aminosyn is also indicated for central vein infusion to prevent or reverse negative nitrogen balance in patients where: (a) the alimentary tract, by the oral, gastrostomy or jejunostomy route cannot or should not be used; (b) gastrointestinal absorption of protein is impaired; (c) metabolic requirements for protein are substantially increased as with extensive burns and (d) morbidity and mortality may be reduced by replacing amino acids lost from tissue breakdown, thereby preserving tissue reserves, as in acute renal failure.

CONTRAINDICATIONS

This preparation should not be used in patients with hepatic coma or metabolic disorders involving impaired nitrogen utilization.

WARNINGS

Intravenous infusion of amino acids may induce a rise in blood urea nitrogen (BUN), especially in patients with impaired hepatic or renal function. Appropriate laboratory tests should be performed periodically and infusion discontinued if BUN levels exceed normal postprandial limits and continue to rise. It should be noted that a modest rise in BUN normally occurs as a result of increased protein intake.

Administration of amino acid solutions to a patient with hepatic insufficiency may result in serum amino acid imbalances, metabolic alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.

Administration of amino acid solutions in the presence of impaired renal function may augment an increasing BUN, as does any protein dietary component.

Solutions containing sodium ion should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency and in clinical states in which there exists edema with sodium retention.

Solutions which contain potassium ion should be used with great care, if at all, in patients with hyperkalemia, severe renal failure and in conditions in which potassium retention is present.

Solutions containing acetate ion should be used with great care in patients with metabolic or respiratory alkalosis. Acetate should be administered with great care in those conditions in which there is an increased level or an impaired utilization of this ion, such as severe hepatic insufficiency.

Hyperammonemia is of special significance in infants, as it can result in mental retardation. Therefore, it is essential that blood ammonia levels be measured frequently in infants.

Instances of asymptomatic hyperammonemia have been reported in patients without overt liver dysfunction. The mechanisms of this reaction are not clearly defined, but may involve genetic defects and immature or subclinically impaired liver function.

Aminosyn can be infused simultaneously with fat emulsion by means of a Y-connector located near the infusion site using separate flow rate controls for each solution.

Aminosyn 5%, 7%, 8.5% and 10% contain potassium metabisulfite; Aminosyn 3.5% contains sodium hydrosulfite, sulfites that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

PRECAUTIONS

Special care must be taken when administering glucose to provide calories in diabetic or prediabetic patients.

Because of its antianabolic activity, concurrent administration of tetracycline may reduce the potential anabolic effects of amino acids infused with dextrose as part of a parenteral feeding regimen.

Feeding regimens which include amino acids should be used with caution in patients with history of renal disease, pulmonary disease, or with cardiac insufficiency so as to avoid excessive fluid accumulation.

The effect of infusion of amino acids, without dextrose, upon carbohydrate metabolism of children is not known at this time.

Nitrogen intake should be carefully monitored in patients with impaired renal function.

For long-term total nutrition, or if a patient has inadequate fat stores, it is essential to provide adequate exogenous calories concurrently with the amino acids. Concentrated dextrose solutions are an effective source of such calories. Such strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava.

ADVERSE REACTIONS

Peripheral Infusions

A 4.25 or 5% solution of amino acids (without additives) is slightly hypertonic. A 3.5% concentration of amino acids (without additives) is slightly hypertonic. Local reactions consisting of a warm sensation, 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.

OVERDOSAGE

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

DOSAGE AND ADMINISTRATION

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.

1. Peripheral Vein Nutritional Maintenance

   Aminosyn® 3.5% (a crystalline amino acid solution) together with dextrose in concentrations of 5% to 10% is suitable for administration by peripheral vein. This solution is not intended for central vein infusion since it does not contain adequate amounts of amino acids or electrolytes for administration with high concentrations of dextrose. Aminosyn 7%, 8.5% or 10% may be diluted with sterile water for injection or 5 to 10% Dextrose Injection to achieve a final amino acid concentration of 3.5, 4.25 or 5% for peripheral administration.

   For peripheral intravenous infusion, 1.0 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.

2. 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 coinfused with a fat emulsion by peripheral vein to provide approximately 1400 to 2000 kcal/day. Fat emulsion coadministration 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 EFAD in patients maintained on fat-free total parenteral nutrition.

Aminosyn 5%, 7% (with or without electrolytes), 8.5% and 10% solutions 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 separately to provide part of the calories, if desired.

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 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 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.

Calcium and phosphorus are added to the solution as indicated. The usual dose of phosphate added to a liter of TPN solution (containing 25% dextrose) is 12 mM. This requirement is related to the carbohydrate calories delivered. Iron is added to the solution or given intramuscularly in depot form as indicated. Vitamin B12, vitamin K and folic acid are given intramuscularly or added to the solution as desired.

Calcium and phosphate additives are potentially incompatible when added to the TPN admixture. However, if one additive is added to the amino acid bottle, and the other to the bottle of concentrated dextrose, and if the contents of both bottles are swirled before they are combined, then the likelihood of physical incompatibility is reduced.

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, the 7%, 8.5% or 10% solution is used in equal volume with 50% dextrose to provide an admixture containing 3.5%, 4.25% or 5% amino acids and 25% dextrose.

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 10% 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 insure 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 bottles containing 250 or 500 mL. Such a solution given at the rate of 145 mL/kg/day provides 130 kcal/kg/day.

HOW SUPPLIED

*Provides sufficient volume to withdraw 1050 mL.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. It is recommended that the product be stored at room temperature (25°C); however, brief exposure up to 40°C does not adversely affect the product. Avoid exposure to light.

Rev: October, 2004

HOSPIRA, INC., LAKE FOREST, IL 60045 USA