5.4% NephrAmine® (Essential Amino Acid Injection) is a sterile, nonpyrogenic solution containing crystalline essential amino acids plus histidine. Each 250 mL unit provides Rose's recommended daily intake of essential amino acids 1 plus 625 mg of histidine, considered essential for uremics. The total nitrogen content of a 250 mL unit is approximately 1.6 grams (10 g of protein equivalent) in 14 grams of amino acids. All amino acids designated USP are the "L" isomer.
Each 100 mL contains:
Histidine USP* ........................................ 0.25 g
Isoleucine USP ........................................ 0.56 g
Leucine USP ........................................... 0.88 g
Lysine ..................................................... 0.64 g
(added as Lysine Acetate USP ............. 0.90 g)
Methionine USP ...................................... 0.88 g
Phenylalanine USP ................................... 0.88 g
Threonine USP ........................................ 0.40 g
Tryptophan USP ..................................... 0.20 g
Valine USP .............................................. 0.64 g
Cysteine .............................................. <0.014 g
(as Cysteine HCl·H 2 O USP ................ <0.020 g)
Sodium Bisulfite (as an antioxidant) ........ <0.05 g
Water for Injection USP ................................ qs
pH adjusted with Sodium Hydroxide NF as required
pH: 6.5 (6.0-7.0); Calculated Osmolarity: 435 mOsmol/liter
Total Nitrogen: Approx. 0.65 g/100 mL
Concentration of Electrolytes (mEq/liter): Sodium 5
Chloride <3; Acetate Approx. 44
*Histidine is considered an essential amino acid in uremic patients
1 Rose WC: The sequence of events leading to the establishment of the amino acid needs of man. Am J Public Health; 1968: 58(11): 2020-2027
NephrAmine® provides an intravenously compatible mixture of essential amino acids which, when infused with hypertonic dextrose as a source of calories, plus electrolytes, minerals, and vitamins, provides in a small volume of fluid all ingredients (with the exception of essential fatty acids) needed for total parenteral nutrition in patients with renal disease.
Infusion of NephrAmine® and hypertonic dextrose provides essential amino acids and calories for protein synthesis to promote improved cellular metabolic balance. Infusion of these components can decrease the rate of rise of blood urea nitrogen (bun) and minimize deterioration of serum potassium, magnesium and phosphorus balance in patients with impaired renal function. The extent to which essential amino acids and calories promote incorporation of waste urea nitrogen into newly synthesized amino acids in man, as it does in experimental animals, is, so far, not established.
The accelerated decrease in serum creatinine levels seen in patients with limited extra-renal complications suggests that treatment with NephrAmine® and hypertonic dextrose leads to earlier return of renal function in patients with potentially reversible acute renal failure. By providing nutritional support and promoting biochemical improvement as well as earlier return of renal function, NephrAmine® and hypertonic dextrose decrease morbidity associated with acute renal failure.
It is thought that acetate from lysine acetate, under the condition of parenteral nutrition, does not impact net acid-base balance when renal and respiratory functions are normal. Clinical evidence seems to support this thinking; however, confirmatory experimental evidence is not available.
The amounts of sodium and chloride present are not of clinical significance.
5.4% NephrAmine® (Essential Amino Acid Injection) is indicated for adult and pediatric use, in conjunction with other measures, to provide nutritional support for uremic patients, particularly when oral nutrition is infeasible or impractical. See Special Precautions in Pediatric Patients for additional information.
NephrAmine® is contraindicated in patients with severe, uncorrected electrolyte and acid-base imbalance, hyperammonemia, decreased (subcritical) circulating blood volume, inborn errors of amino acid metabolism, or hypersensitivity to one or more amino acids present in the solution.
This product contains sodium bisulfite, 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.
Safe and effective use of central venous nutrition requires a knowledge of nutrition as well as clinical expertise in recognition and treatment of the complications which can occur. Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of central venous nutrition. Studies should include blood sugar, serum proteins, kidney and liver function tests, electrolytes, hemogram, carbon dioxide combining power, serum osmolarity, blood cultures, blood ammonia levels, and circulating blood volume.
NephrAmine® does not replace dialysis and conventional supportive therapy in patients with renal failure.
Administration of NephrAmine® to children or low birth-weight infants, especially in high doses, may result in hyperammonemia.
Clinically significant hypokalemia, hypophosphatemia, or hypomagnesemia may occur as a result of therapy with NephrAmine® and hypertonic dextrose and replacement therapy may become necessary.
Administration of nitrogen in any form to patients with marked hepatic insufficiency or hepatic coma may result in plasma amino acid imbalances, hyperammonemia, or central nervous system deterioration. NephrAmine® should, therefore, be used with caution in such patients.
The intravenous administration of these solutions can cause fluid and/or solute overload resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. The risk of dilutional states is inversely proportional to the solute concentration of the solution infused. The risk of solute overload causing congested states with peripheral and pulmonary edema is directly proportional to the concentration of the solution.
Conservative doses of amino acids should be given, dictated by the nutritional status of the patient.
Clinical evaluation and periodic laboratory determinations are necessary to monitor changes in fluid balance, electrolyte concentrations, and acid-base balance during prolonged parenteral therapy or whenever the condition of the patient warrants such evaluation. Significant deviations from normal concentrations may require the use of additional electrolyte supplements.
In order to promote urea nitrogen reutilization in patients with renal failure, it is essential to provide adequate calories with minimal amounts of the essential amino acids, and to severely restrict the intake of nonessential nitrogen. Hypertonic dextrose solutions are a convenient and metabolically effective source of concentrated calories.
Fluid balance must be carefully monitored in patients with renal failure and care should be taken to avoid circulatory overload, particularly in association with cardiac insufficiency.
In patients with myocardial infarct, infusion of amino acids should always be accompanied by dextrose, since in anoxia, free fatty acids cannot be utilized by the myocardium, and energy must be produced anaerobically from glycogen or glucose.
Strongly hypertonic nutrient solutions should be administered through an indwelling intravenous catheter with the tip located in the superior vena cava.
Special care must be taken when giving hypertonic dextrose to glucose-intolerant patients such as diabetic or prediabetic and uremic patients; especially when the latter are receiving peritoneal dialysis. To prevent severe hyperglycemia in such patients, insulin may be required.
Administration of glucose at a rate exceeding the patient' utilization may lead to hyperglycemia, coma, and death.
Administration of amino acids without carbohydrates may result in the accumulation of ketone bodies in the blood. Correction of this ketonemia may be achieved by the administration of carbohydrates. Abrupt cessation of hypertonic dextrose infusion may result in rebound hypoglycemia.
When 5.4% NephrAmine® (Essential Amino Acid Injection) is subjected to changes in temperature, there is a chance that some transient crystallization of amino acids may occur. Thorough shaking of the bottle for about one minute should redissolve the amino acids. If the amino acids do not completely redissolve, the bottle must be rejected.
To minimize the risk of possible incompatibilities arising from mixing this solution with other additives that may be prescribed, the final infusate should be inspected for cloudiness or precipitation immediately after mixing, prior to administration, and periodically during administration.
Use only if solution is clear and vacuum is present.
Pregnancy Category C. Animal reproduction studies have not been conducted with 5.4% NephrAmine® (Essential Amino Acid Injection). It is also not known whether NephrAmine® can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. NephrAmine® should be given to a pregnant woman only if clearly needed.
Administration by central venous catheter should be used only by those familiar with this technique and its complications.
Central venous nutrition may be associated with complications which can be prevented or minimized by careful attention to all aspects of the procedure including 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.
SEE PACKAGE INSERT FOR ADDITIONAL INFORMATION ON CENTRAL VENOUS ADMINISTRATION.
Frequent laboratory studies are necessary in patients with renal insufficiency due to underlying metabolic abnormalities. Hyperglycemia, a frequent complication, may not be reflected by glycosuria in renal failure. Blood glucose, therefore, must be determined frequently, often every six hours to guide dosage of dextrose and insulin if required.
Serum concentrations of potassium, phosphorus, and magnesium may dramatically decline with successful treatment, individually or together; these substances should be supplemented as required. Special care must be taken to avoid hypokalemia in digitalized patients, or those with cardiac arrhythmias.
5.4% NephrAmine® (Essential Amino Acid Injection) should be used with special caution in pediatric patients, especially low birth-weight infants, due to limited clinical experience.
Laboratory and clinical monitoring of pediatric patients, especially when nutritionally depleted, must be extensive and frequent. Initial total daily dose should be low, and increased slowly. Dosage of NephrAmine® above one gram of essential amino acids per kilogram body weight per day is not recommended.
Frequent monitoring of blood glucose is required in low birth-weight or septic infants as infusion of hypertonic dextrose carries a greater risk of hyperglycemia in such patients.
The absence of arginine in NephrAmine® may accentuate the risk of hyperammonemia in infants.
See and Special Precautions for Central Venous Nutrition .
Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis, and hypervolemia.
Symptoms may result from an excess or deficit of one or more of the ions present in the solution infused, therefore, frequent monitoring of electrolyte levels is essential.
Infrequent instances of hyperammonemia have been reported following administration of essential amino acid solutions to patients with massive gastrointestinal hemorrhage, nonuremic infants and children or following administration of higher than recommended doses to adult or pediatric patients. Serum ammonia levels and clinical symptoms may subside when the infusions are discontinued.
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.
In the event of a fluid or solute overload during parenteral therapy, reevaluate the patient' condition, and institute appropriate corrective treatment.
The objective of nutritional management of renal decompensation is the provision of sufficient amino acid and caloric support for protein synthesis without greatly exceeding the renal capacity to excrete metabolic wastes.
Three grams of nitrogen per day provided as essential amino acids with adequate calories produce nitrogen equilibrium in many stable patients with chronic uremia. Although nitrogen requirements may be higher in stressed or acutely uremic patients, or those on dialysis, provision of additional nitrogen may not be possible due to fluid intake limits or glucose intolerance.
The usual methods of determining individual patient requirements for amino acids such as nitrogen balance or daily body weight are difficult to perform or interpret in the uremic patient. Therefore, dosage is guided by the patient' fluid intake limits and glucose and nitrogen tolerances, as well as metabolic and clinical response. Rate of rise of blood urea nitrogen generally diminishes with infusion of essential amino acids. However, excessive intake of dietary protein or increased protein catabolism may alter this response.
Adults: Generally, 250 to 500 mL of 5.4% NephrAmine® (Essential Amino Acid Injection), containing approximately 1.6 to 3.2 grams of nitrogen (in 13.4 to 26.8 grams of essential amino acids), are given daily. Adequate calories should be provided simultaneously. Each 250 mL of NephrAmine® is typically mixed aseptically with 500 mL of 70% dextrose to yield a solution of 1.8% NephrAmine® in 47% dextrose. This mixture provides a calorie-to-nitrogen ratio of 744:1.
Children: Initial total daily dose should be low and increased slowly. Dosage of NephrAmine® above one gram of essential amino acids per kg of body weight per day is not recommended. See Special Precautions in Pediatric Patients for additional information.
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.
Electrolyte supplementation may be required. Undiluted NephrAmine® contains 5 mEq/liter of sodium. Elevated serum potassium, phosphorus, and magnesium levels generally decrease during treatment with NephrAmine®. Although these effects are beneficial, especially in acute renal failure, in some instances the reduction may be so great that supplementation of these electrolytes is required, especially in the presence of cardiac arrhythmias or digitalis toxicity. During periods of anuria or oliguria, electrolyte supplementation should be done with caution, even if serum levels are in the low normal range.
Compatibility of electrolyte additives to the 5.4% NephrAmine® (Essential Amino Acid Injection)/hypertonic dextrose mixture must be considered, and potentially incompatible ions such as calcium and phosphate may be added to alternate infusion bottles to avoid precipitation. In patients with hyperchloremic or other metabolic acidosis, sodium and potassium may be added as acetate or lactate salts to provide bicarbonate precursor. The electrolyte content of NephrAmine® must be considered when calculating daily electrolyte intake. Serum electrolytes, including magnesium and phosphorus, should be monitored frequently.
If a patient' nutritional intake is primarily parenteral, vitamins, especially the water soluble vitamins, should also be provided.
Hypertonic mixtures of essential 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, generally 20-30 mL/hour. Increases by increments of 10 mL/hour each 24 hours are recommended to a maximum of 60-100 mL/hour. If administration rate should fall behind schedule, no attempt to "catch up" to planned intake should be made.
Administration rate is governed by the patient' nitrogen, fluid, and glucose tolerance. Uremic patients are frequently glucose intolerant, especially in association with peritoneal dialysis, and may require the administration of exogenous insulin to prevent hyperglycemia. Blood glucose levels must be determined frequently. 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.
Care must be taken to avoid incompatible admixtures. Consult with pharmacist.
5.4% NephrAmine® (Essential Amino Acid Injection) is supplied sterile and nonpyrogenic in glass containers packaged 12 per case.
NDC No.: 54391-1909-5 Size: 250 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. Protect from light until use.
Manufactured By B. Braun Medical, Inc. For R&D Laboratories, Inc.
For Medical Emergencies:
(800) 854-6851