Aminosyn II and Dextrose

Upper Chamber: Aminosyn II 7%, an amino acid injection, 500 mL.

Aminosyn II 7% is a sterile, nonpyrogenic solution for intravenous infusion. The formulation is described in the table below.

Lower Chamber: 50% Dextrose Injection, USP, 500 mL.

50% Dextrose Injection, USP (concentrated dextrose in water) is a sterile, nonpyrogenic, hypertonic solution of Dextrose, USP in water for injection. The table below indicates the characteristics of this concentrated solution.

The container must be used only after removing the clamp and thoroughly mixing the contents of the two chambers. The solution resulting from mixing the contents of the upper and the lower chamber will be 3.5% amino acids in 25% dextrose. Mixing the contents of the upper and lower chambers yields a concentrated source of amino acids and carbohydrate calories for intravenous infusion. Headspace contains Nitrogen gas. The composition of this admixture is described in the table below.

The formulas for the individual amino acids present are as follows:

Dextrose, USP is chemically designated D-glucose, monohydrate (C6H12O6 • H20), a hexose sugar freely soluble in water.

The flexible plastic container is fabricated from a specially formulated nonplasticized thermoplastic co-polyester (CR3). Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions inside the plastic container also can leach out certain of its chemical components in very small amounts before the expiration period is attained. However, the safety of the plastic has been confirmed by tests in animals according to USP biological standards for plastic containers.

The Aminosyn II 3.5% in 25% Dextrose Injection admixture, obtained upon mixing thoroughly the contents of the two chambers, provides carbohydrate calories and crystalline amino acids to stimulate protein synthesis, to limit protein catabolism, to minimize liver glycogen depletion and to promote wound healing. The infusion of this mixture through a central venous line should be considered to meet protein and calorie requirements for patients requiring prolonged total parenteral nutrition. I.V. lipids may be infused simultaneously to provide adequate calories, if desired.

The Aminosyn II 3.5% in 25% Dextrose Injection admixture is hypertonic and may not be administered by peripheral vein.

Concentrated dextrose solutions, if administered too rapidly, may result in significant hyperglycemia and possible hyperosmolar syndrome, characterized by mental confusion and loss of consciousness.

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 solution 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 containing potassium ions 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.

Aminosyn II 3.5% in 25% Dextrose Injection contains sodium hydrosulfite, a sulfite 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.

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.

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

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.

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

The total daily dose of Aminosyn II 3.5% in 25% Dextrose Injection to be infused depends on daily protein and caloric 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.

As reported in the literature, the dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low birth weight infants, because of the increased risk of hyperglycemia/hypoglycemia.

As with all intravenous fluid therapy, the parenteral administration of a solution of amino acids and dextrose requires an accurate estimate of the total fluid, electrolytes and acid-base needed to compensate for the patient’s measurable urinary and other (i.e., nasogastric suction, fistula drainage, diarrhea) daily losses. After estimating the total daily fluid (water) requirements, the appropriate volume to be infused to meet the daily protein requirement of the patient, can be determined. The balance of fluid needed beyond the volume of the amino acid/dextrose solution can be provided by other solutions suitable for intravenous infusion. I.V. lipid emulsions may also be infused to deliver additional calories if required. Lipid emulsion can be administered to provide up to 3 g fat/kg/day, infused simultaneously with Aminosyn II 3.5% in 25% Dextrose Injection by means of a Y-connector located near the infusion site, using separate flow controls for each solution. Aminosyn II 3.5% in 25% Dextrose Injection should not be premixed with fat emulsions. Vitamins and trace minerals may be added to the amino acid/dextrose solution as needed.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The total daily dose of amino acid/dextrose solution to be infused depends on daily protein requirements and on the patient’s metabolic and clinical response. The daily determination of nitrogen balance and accurate body weights, corrected for fluid balance, are probably the best means of assessing individual protein requirements.

Adults

The daily nutrient requirements of an average adult patient, not hypermetabolic, in an acceptable weight range and with restricted physical activity, are about 30 kcal/kg of body weight, 12 to 18 grams of nitrogen and between 2500 and 3000 mL of fluids. In depleted and severely traumatized patients such as burned patients or patients who have received major surgery with complications, the requirements for nutrients and fluids may be significantly higher. In such cases, 4000 calories and 25 grams of nitrogen or more may be required daily to achieve nitrogen balance. The fluid losses through drainages and wound surface must be taken into account in calculating the fluid requirements of these patients.

Fat emulsion administration should be considered when prolonged 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.

Each gram of dextrose provides approximately 3.4 calories   1000 mL of Aminosyn II 3.5% in 25% Dextrose Injection will provide 5.6 grams of nitrogen and 850 calories. The infusion rate of Aminosyn II 3.5% in 25% Dextrose Injection should be 2 mL/min initially and may be gradually increased to deliver the required amounts of amino acids and calories. If nutrient administration falls behind schedule, under no circumstances should an attempt to “catch up” to planned intake be made. The rate of nutrient infusion is governed by the protein requirements and by the patient’s glucose tolerance estimated by glucose levels in plasma and urine. The maximum rate at which dextrose can be infused without producing glycosuria is 0.5 g/kg/hour; at a rate of 0.8 g/kg/hour, about 95% of the infused dextrose is retained. Administration of exogenous insulin may be required in order to control hyperglycemia and glycosuria which may occur upon infusion of concentrated glucose solutions. When concentrated dextrose infusion is abruptly interrupted rebound hypoglycemia may occur, which can be prevented by the administration of 5% or 10% dextrose solutions. Part of the caloric requirements may be met by the infusion of I.V.fat emulsions.

SERUM ELECTROLYTES SHOULD BE MONITORED AS INDICATED. Electrolytes should 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. Adding 20 mL of TPN Electrolytes (List 5779) to the amino acid chamber and 5 mL of Potassium Phosphate (List 7296) to the dextrose chamber will result in final admixture concentrations (in mEq/L) as follows: 53 sodium, 42 potassium, 35 chloride, 5 magnesium, 4.5 calcium, 54.7 acetate, and 15 (mM) phosphate. Alternate electrolyte additives may be used at the clinician’s discretion.

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 solution, and the other to the concentrated dextrose solution, and if the contents of both chambers are mixed 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.

Pediatric

Pediatric requirements for parenteral nutrition are constrained by the greater relative fluid requirements of the infant and greater caloric requirements per kilogram. A 3.5% amino acid solution is too concentrated for use in pediatric patients less than 1 year old, who generally require a 2.5% amino acid solution. However, older pediatric patients can receive Aminosyn II 3.5% in 25% Dextrose Injection. The suggested amino acid dosage level for children between 4 and 12 years of age is 2 g/kg/day; for 13 to 15 years of age, 1.7 g/kg/day; and for 16 years of age and above, 1.5 g/kg/day. Energy requirements for children between 1 and 7 years of age are approximately 75 to 90 kcal/kg/day; for children 7 to 12 years of age, 60 to 75 kcal/kg/day; and for ages 12 to 18 years, 30 to 60 kcal/kg/day. Energy intake may be supplemented with intravenous fat emulsion. In cases of malnutrition or stress, these requirements may be increased.

Supplemental electrolytes and vitamin additives should be administered as deemed necessary by careful monitoring of blood chemistries and nutritional status. Iron supplementation is more critical in the child than the adult because of the increasing red cell mass required by the growing child. 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 children, accurately calibrated and reliable infusion systems should be used.

Drug Interactions

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store.

INSTRUCTIONS FOR USE

DO NOT USE IF AMINOSYN II IS DISCOLORED OR IF CLAMP IS OPEN OR MISSING. COLOR VARIATION IN THE DEXTROSE INJECTION FROM PALE YELLOW TO YELLOW IS NORMAL AND DOES NOT ALTER EFFICACY.

To Open:

Tear outer wrap at notch. After removing the overwrap, check for minute leaks by squeezing the container firmly. If leaks are found, discard solution as sterility may be impaired. If supplemental medication is desired, follow directions below before preparing for administration.

To Add Medication:

1. Prepare the appropriate additive port.

2. Using aseptic technique and an additive delivery needle of appropriate length, puncture resealable additive port at target area through inner diaphragm and inject. Withdraw needle after injecting medication.

3. The additive ports should be protected by covering with additive caps.

4. Mix container contents thoroughly.

Preparation for Administration

(Use aseptic technique)

1. Open clamp between the two chambers. Completely drain all the solution and air into the lower chamber. To achieve this, stretch the side wall of the emptied top chamber.

2. Close flow control clamp of administration set.

3. Remove cover from outlet port at bottom of container.

4. Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. NOTE: See full directions on administration set carton.

5. Suspend from hanger at top of container.

6. Squeeze and release drip chamber to establish proper fluid level in chamber.

7. Open flow control clamp to expel air from set. Close flow control clamp.

8. Connect to central infusion catheter.

9. Regulate rate of administration with flow control clamp. Ensure that all solution and air are in the lower chamber when reading fluid levels.

WARNING: Do not use flexible container in series connections.