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
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's 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.
Drug product contains no more than 25 μg/L of
Frequent clinical evaluation and laboratory
determinations are necessary for proper monitoring during administration.
Laboratory tests should include measurement of blood
sugar, electrolyte, and serum protein concentrations, kidney and liver function
tests, and evaluation of acid-base balance and fluid balance.
Other laboratory tests may be suggested by the patient's
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No in vitro or in vivo carcinogenesis, mutagenesis, or
fertility studies have been conducted with 5.4% NephrAmine® (Essential Amino
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.
Labor And Delivery
Information is unknown.
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk, caution should be
exercised when NephrAmine® is administered to a nursing woman.
Safety and effectiveness of amino acid injections in
pediatric patients have not been established by adequate and well-controlled
studies. However, the use of amino acid injections in pediatric patients as an
adjunct in the offsetting of nitrogen loss or in the treatment of negative
nitrogen balance is well established in the medical literature. In pediatric
patients, the final solution should not exceed twice normal serum osmolarity
(718 mOsmol/L). See INDICATIONS AND USAGE, WARNINGS, and DOSAGE
NephrAmine® has not been studied in geriatric patients.
Elderly patients are known to be more prone to fluid overload and electrolyte
imbalance than younger patients. This may be related to impairment of renal
function which is more frequent in an elderly population. As a result the need
for careful monitoring of fluid and electrolyte therapy is greater in the
elderly. All patients, including the elderly, require an individual dose of all
parenteral nutrition products to be determined by the physician on an individual
case-by-case basis, which will be based on body weight, clinical condition and
the results of laboratory monitoring tests. There is no specific geriatric
dose. See WARNINGS.
Special Precautions For Central Venous Nutrition
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.
Although a detailed discussion of the complications of
central venous nutrition is beyond the scope of this insert, the following
summary lists those based on current literature:
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 as well as recognition and treatment of complications.
For details of techniques 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 arterio-venous
fistula, phlebitis, thrombosis, and air and catheter embolus.
The constant risk of sepsis is present during central
venous nutrition. Since contaminated solutions and infusion catheters are
potential sources of infection, it is imperative that the preparation of
parenteral nutrition solutions and the placement and care of catheters be
accomplished under controlled aseptic conditions.
Parenteral nutrition solutions should ideally be prepared
in the hospital pharmacy under a laminar flow hood. The key factor in their
preparation is careful aseptic technique to avoid inadvertent touch contamination
during mixing of solutions and subsequent admixtures.
Parenteral nutrition solutions should be used promptly
after mixing. Any storage should be under refrigeration for as brief a time as
possible. Administration time for a single bottle and set should never exceed
Consult the medical literature for a discussion of the
management of sepsis during central venous nutrition. In brief, typical
management includes replacing the solution being administered with a fresh container
and set, and the remaining contents are cultured for bacterial or fungal
contamination. If sepsis persists and another source of infection is not
identified, the catheter is removed, the proximal tip cultured, and a new
catheter reinserted when the fever has subsided. Nonspecific, prophylactic antibiotic
treatment is not recommended. Clinical experience indicates that the catheter
is likely to be the prime source of infection as opposed to aseptically
prepared and properly stored solutions.
The following metabolic complications have been reported:
metabolic acidosis, hypophosphatemia, alkalosis, hyperglycemia and glycosuria,
osmotic diuresis and dehydration, rebound hypoglycemia, elevated liver enzymes,
hypo- and hypervitaminosis, electrolyte imbalances, and elevated plasma amino acid
levels and hyperammonemia in infants and pediatric patients. Frequent clinical
evaluation and laboratory determinations are necessary, especially during the
first few days of central venous nutrition, to prevent or minimize these
Special Precautions In Patients With Renal Insufficiency
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
Special Precautions In Pediatric Patients
5.4% NephrAmine® (Essential Amino Acid Injection) should
be used with special caution in pediatric patients, due to limited clinical
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
For infants, especially neonates and low birth weight
infants, amino acid formulations developed specifically for nutritional support
of infants and pediatric patients should be considered. If NephrAmine® is administered
to these very young patients, extra caution in frequent monitoring of plasma
amino acid levels and serum ammonia is strongly recommended.
Frequent monitoring of blood glucose is required in
neonates, 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.
In pediatric patients, the final solution should not
exceed twice normal serum osmolarity (718 mOsmol/L).