Aminosyn II in Dextrose Injection

Patient Information

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Description

Upper Chamber: Aminosyn II.

Aminosyn II (an amino acid injection) is a sterile, nonpyrogenic solution for intravenous infusion.

Lower Chamber: Dextrose Injection, USP.

Dextrose Injection, USP (concentrated dextrose in water) is a sterile, nonpyrogenic, hypertonic solution of Dextrose, USP in water for injection.

The container must be used only after opening the clamp and thoroughly mixing the contents of the two chambers. Mixing the contents of the upper and lower chamber yields a concentrated source of amino acids and carbohydrate calories for intravenous infusion. Headspace contains Nitrogen gas. The composition of these admixtures is described in the table below.

SOLUTION COMPOSITION BEFORE COMBINATION

SOLUTION COMPOSITION BEFORE COMBINATION

SOLUTION COMPOSITION AFTER COMBINATION (1000 mL)

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

Essential Amino Acids
Isoleucine	CH3CH2CH(CH3)CH(NH2)COOH
Leucine	(CH3)2CHCH2CH(NH2)COOH
Lysine Acetate	H2N(CH2)4CH(NH2)COOH • CH3COOH
Methionine	CH3S(CH2)2CH(NH2)COOH
Phenylalanine	CH2CH(NH2)COOH
Threonine	CH3CH(OH)CH(NH2)COOH
Tryptophan	CH2CH(NH2)COOH
Valine	(CH3)2CHCH(NH2)COOH
Nonessential Amino Acids
Alanine	CH3CH(NH2)C H
Arginine	H2NC(NH)NH(CH2)3CH(NH2)C H
L-Aspartic Acid	HOOCCH2CH(NH2)COOH
L-Glutamic Acid	HOOC(CH2)2CH(NH2)COOH
Glycine	H2NCH2COOH
Histidine	CH2CH(NH2)COOH
Proline
Serine	HOCH2CH(NH2)COOH
N-Acetyl-L-Tyrosine

Dextrose, USP is chemically designated D-glucose, monohydrate (C₆H₁₂O₆• H₂O), 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.

Aminosyn II in Dextrose Injection is indicated for intravenous infusion to prevent nitrogen loss and negative nitrogen balance in cases where (a) the gastrointestinal tract by the oral, gastrostomy or jejunostomy route cannot or should not be used, (b) gastrointestinal absorption of nutrients is impaired or (c) metabolic requirements for protein and calories 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. In such patients intravenous feeding for more than a few days would be expected.

The addition of supplemental electrolytes, multivitamins, and trace metal additives will be required in accordance with the prescription of the attending physician.

Dosage And Administration

The total daily dose of Aminosyn II in Dextrose (amino acid injection in dextrose injection) Injection to be infused depends on daily protein and caloric requirements and on the patient’s metabolic and clinical response. Aminosyn II in Dextrose (amino acid injection in dextrose injection) Injection is administered intravenously. It may be administered by peripheral or central vein, depending upon the dextrose concentration. Peripheral vein administration of Aminosyn II 3.5% in 5% Dextrose Injection (with electrolytes added per the physician’s prescription) is appropriate. However, simultaneous administration with intravenous fat emulsion is recommended, both to reduce the final admixture osmolarity, and to provide additional calories.

Peripheral vein administration of Aminosyn II 4.25% in 10% Dextrose Injection (with electrolytes added) is not recommended unless fat emulsion is delivered simultaneously. The high solution osmolarity (894 mOsmol/L) will likely provoke vein irritation if the solution is administered without fat emulsion.

Solutions of Aminosyn II in 20% or 25% Dextrose Injection are intended only for central venous administration. 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. 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, electrolyte and acid-base needs 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 daily determination of nitrogen balance and accurate body weights, corrected for fluid balance, are probably the best means of assessing individual protein requirements. The balance of fluid needed beyond the volume of the amino acid/dextrose solution can be provided by other solutions suitable for intravenous infusion. 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.

Adult Patients

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 (or 1.0 to 1.5 g amino acid/kg/day) 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.

Nutritional admixtures with a final dextrose concentration greater than 10% must be administered by central vein. Peripheral vein administration of Aminosyn II 3.5% in 5% Dextrose Injection or Aminosyn II 4.25% in 10% Dextrose Injection is possible, but simultaneous administration of lipid emulsion is recommended to reduce the osmolarity of the admixture, and to increase the nonprotein energy intake.

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. The infusion rate of Aminosyn II in 20% or 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 requirement may be met by the infusion of I.V. fat emulsion.

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 (multiple electrolyte additive, List 5779) to each 500 mL of the amino acid solution and 4 to 5 mL of Potassium Phosphate (List 7296) to each 500 mL of 40 to 50% dextrose solution will result in final admixture concentrations appropriate for central vein administration. Alternate electrolyte additives may be used at the clinician’s discretion.

Vitamins, including folic acid and vitamin K are required additives. Vitamin K₁ (Phytonadione Injection, USP) is given intramuscularly or added to the solution as desired. The trace element supplements should be given when long-term parenteral nutrition is undertaken. Iron is added to the solution or given intramuscularly in depot form as indicated.

Calcium and phosphate are added to the solution as indicated. The usual dose of phosphate added to a liter of TPN solution (containing 25% dextrose) is 12 to 15 mM. This requirement is related to the carbohydrate calories delivered. If the final admixture contains only 5% or 10% dextrose, then a proportionate reduction in the amount of additive phosphate is recommended. An inorganic phosphate supplement is recommended to facilitate synthesis of high-energy phosphate during dextrose metabolism.

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.

Pediatric Patients

Pediatric requirements for parenteral nutrition are constrained by the greater relative fluid requirements of the child and greater caloric requirements per kilogram. These solutions are too concentrated for use in pediatric patients less than 1 year old, who generally receive a 2.5% amino acid solution. However, older pediatric patients can tolerate amino acids in concentrations of up to 5%. Dosage of amino acids is usually prescribed on a g/kg body weight/day basis, with adjustments for patient age as follows: ages 1 to 3 years, 2 to 2.5 g/kg/day; ages 4 to 12 years, 2 g/kg/day; ages 13 to 15 years, 1.7 g/kg/day; ages 16 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.

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 and remove solution container. Check the container for minute leaks by squeezing firmly. If leaks are found, discard the solution, as sterility may be impaired. If supplemental medication is desired, follow directions below before preparing for administration.

To Add Medication

(Use Aseptic Technique)

Additives may be incompatible. See DOSAGE AND ADMINISTRATION.

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. Close clamp after draining.
2. Agitate container to assure adequate mixing.
3. Prepare lower chamber additive port.
4. Using an aseptic technique, puncture the reseal additive port at the target area through the inner diaphragm with an 18, 19, or 20-gauge additive delivery needle of appropriate length. Inject additive medication.
5. Repeat as necessary. Mix container contents thoroughly after each additive.
6. After use, protect additive ports by covering with additive caps.

Preparation for Administration

(Use Aseptic Technique)

1. 1. If you have not already done so in step 1 above, 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.

1. Close flow control clamp of administration set.
2. Remove cover from outlet port at bottom of container.
3. Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. NOTE: When using a vented administration set, replace bacterial retentive air filter with piercing pin cover. Insert piercing pin with twisting motion until shoulder of air filter housing rests against outlet port flange.
4. Suspend from hanger at top of container.
5. Squeeze and release drip chamber to establish proper fluid level in chamber.
6. Open flow control clamp to expel air from set. Close flow control clamp.
7. Connect to central or peripheral infusion catheter.
8. Regulate rate of administration with an electronic flow-control device.

WARNING: Do not use flexible container in series connections.

How Supplied

The Nutrimix® dual-chamber flexible container provides 500 mL of Aminosyn® II in the upper chamber and 500 mL of Dextrose Injection, USP in the lower chamber. Concentrations provided in the separate chambers and in the combined 1000 mL volume after release of the clamp and mixing are shown below.

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.

To prevent breakage, handle cold or refrigerated (2°C to 8°C) co-polyester (CR3) containers with care.

Hospira, Inc., Lake Forest, IL 60045 USA. Revised: May, 2004. FDA revision date: 2/19/2003

Hyperosmolar syndrome, resulting from excessively rapid administration of concentrated dextrose may cause mental confusion and/or loss of consciousness.

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.

Generalized flushing, fever and nausea also have been reported during peripheral infusions of amino acid solutions. Also see WARNINGS and PRECAUTIONS.

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.

Drug Interactions

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

The Aminosyn II in 20% Dextrose Injection admixture is hypertonic and may not be administered by peripheral vein. Aminosyn II 4.25% in 10% Dextrose Injection is also hypertonic (894 mOsmol/L), but it may be administered by peripheral vein only if intravenous fat emulsion is infused simultaneously.

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

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 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 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 in Dextrose (amino acid injection in dextrose injection) 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.

Special care must be taken when administering glucose to diabetic or prediabetic patients. To control and minimize hyperglycemia and consequent glycosuria, it is desirable to monitor blood and urine glucose and, if necessary, add insulin.

Because of its antianabolic activity, concurrent administration of tetracycline may reduce the nitrogen sparing effects of infused amino acids.

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.

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

Aminosyn II in 20% Dextrose Injection is indicated for long-term total parenteral nutrition and whenever it is essential to provide, together with amino acids, adequate amounts of exogenous calories. Concentrated dextrose is an effective source of such calories. Such strongly hypertonic nutrient solutions should be administered only through an indwelling catheter with the tip located in a large vein: i.e., the superior vena cava.

Central vein infusion of nutrient solutions requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of complications. Attention must be given to solution preparation, administration and patient monitoring. IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL BASED ON CURRENT MEDICAL PRACTICES BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM. SUMMARY HIGHLIGHTS OF COMPLICATIONS (See also Current Medical Literature).

1. Technical
   The placement of a central venous catheter should be regarded as a surgical procedure. One should be fully acquainted with various techniques of catheter insertion. For details of technique and placement sites, consult the medical literature. X-ray is the best means of verifying catheter placement. Complications known to occur from the placement of central venous catheters 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 and catheter emboli.
2. Septic
   The constant risk of sepsis is present during administration of total parenteral nutrition. It is imperative that the preparation of the solution and the placement and care of catheters be accomplished under strict aseptic conditions.Solutions should be used promptly after mixing. Storage should be under refrigeration and limited to a brief period of time, preferably less than 24 hours.Administration time for a single container and set should never exceed 24 hours.
3. Metabolic
   The following metabolic complications have been reported: metabolic acidosis and alkalosis, hypophosphatemia, hypocalcemia, osteoporosis, hyperglycemia, hyperosmolar nonketotic states and dehydration, glycosuria, rebound hypoglycemia, osmotic diuresis and dehydration, elevated liver enzymes, hypo- and hypervitaminosis, electrolyte imbalances and hyperammonemia in children. Frequent evaluations are necessary especially during the first few days of therapy to prevent or minimize these complications.Administration of glucose at a rate exceeding the patient’s utilization rate may lead to hyperglycemia, coma and death.

Pregnancy Category C. Animal reproduction studies have not been conducted with Aminosyn II in Dextrose (amino acid injection in dextrose injection) Injection. It is not known whether this admixture can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Aminosyn II in Dextrose (amino acid injection in dextrose injection) Injection should be given to pregnant women only if clearly needed. Not for use in infants. See CONTRAINDICATIONS and DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical Studies of Aminosyn II in Dextrose (amino acid injection in dextrose injection) Injection have not been performed to determine whether patients over 65 years of age respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by kidney, and the risk for adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Usage

Due to their concentration, these solutions are not recommended for use in pediatric patients less than 1 year old. Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants.

CLINICAL EVALUATION AND LABORATORY DETERMINATIONS, AT THE DISCRETION OF THE ATTENDING PHYSICIAN, ARE NECESSARY FOR PROPER MONITORING DURING ADMINISTRATION. Do not withdraw venous blood for blood chemistries through the infusion site, as interference with estimations of nitrogen-containing substances may occur. Blood studies should include glucose, urea nitrogen, serum electrolytes, ammonia, triglycerides, acid-base balance, serum proteins, kidney and liver function tests, osmolarity and hemogram. White blood count and blood cultures are to be determined if indicated. Urinary osmolality and glucose should be determined as necessary.

Do not use unless the solutions are clear and container is undamaged. Discard unused portion.

This product contains no more than 25 mcg/L of aluminum.

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

Contraindications

This preparation should not be used in patients with hepatic coma or metabolic disorders involving impaired nitrogen utilization. These solutions are too concentrated for use in infants.

The Aminosyn II in 20% 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 in 10% Dextrose, obtained upon mixing thoroughly the contents of the two chambers, provides a hypocaloric energy intake with amino acids for peripheral vein administration. When administered with intravenous fat emulsion, such admixtures can approximate the usual oral nutritional intake.