Included as part of the PRECAUTIONS section.
Pulmonary Embolism Due To Pulmonary Vascular Precipitates
Pulmonary vascular precipitates causing pulmonary
vascular emboli and pulmonary distress have been reported in patients receiving
PN. In some fatal cases, pulmonary embolism occurred as a result of calcium
phosphate precipitates. Precipitation following passage through an in-line
filter and suspected in vivo precipitate formation has also been reported. If
signs of pulmonary distress occur, stop the PN infusion and initiate a medical
evaluation. In addition to inspection of the solution [see DOSAGE AND
ADMINISTRATION], the infusion set and catheter should also periodically be
checked for precipitates.
Vein Damage And Thrombosis
ELCYS must be diluted and used as an admixture in PN
solutions. It is not for direct intravenous infusion. Solutions with an
osmolarity of 900 mOsm/L or greater must be infused through a central catheter [see
DOSAGE AND ADMINISTRATION]. The infusion of hypertonic nutrient injections
into a peripheral vein may result in vein irritation, vein damage, and/or
thrombosis. The primary complication of peripheral access is venous thrombophlebitis,
which manifests as pain, erythema, tenderness or a palpable cord. Remove the
catheter as soon as possible, if thrombophlebitis develops.
Increased Blood Urea Nitrogen (BUN)
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 in the presence of
impaired renal function may augment an increasing BUN, as does any protein
Administration of ELCYS may result in metabolic acidosis
in preterm infants.
Administration of amino acid solutions to a patient with
hepatic impairment may result in serum amino acid imbalances, metabolic
alkalosis, prerenal azotemia, hyperammonemia, stupor and coma.
Frequent clinical evaluation and laboratory
determinations are necessary for proper monitoring of acid-base balance during
parenteral nutrition therapy. Significant deviations from normal concentrations
may require the use of additional electrolyte supplements.
Hepatobiliary disorders are known to develop in some
patients without preexisting liver disease who receive PN, including
cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis and cirrhosis,
possibly leading to hepatic failure. The etiology of these disorders is thought
to be multifactorial and may differ between patients.
Monitor liver function parameters and ammonia levels.
Patients developing signs of hepatobiliary disorders should be assessed early
by a clinician knowledgeable in liver diseases in order to identify possible
causative and contributory factors, and possible therapeutic and prophylactic
Hyperammonemia is of special significance in infants, as
it can result in neurocognitive delays. 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 [see CONTRAINDICATIONS, Use In
ELCYS contains aluminum that may be toxic.
Aluminum may reach toxic levels with prolonged parenteral
administration in patients with renal impairment. Preterm infants are
particularly at risk for aluminum toxicity because their kidneys are immature,
and they require large amounts of calcium and phosphate solutions, which also
Patients with renal impairment, including preterm
infants, who receive greater than 4 to 5 mcg/kg/day of parenteral aluminum can
accumulate aluminum to levels associated with central nervous system and bone
toxicity. Tissue loading may occur at even lower rates of administration.
Exposure to aluminum from ELCYS is not more than 0.21
mcg/kg/day when preterm and term infants less than 1 month of age are
administered the recommended maximum dosage of ELCYS (15 mg cysteine/g of amino
acids and 4 g of amino acids/kg/day) [see Table 1, DOSAGE AND ADMINISTRATION].
When prescribing ELCYS for use in PN containing other small volume parenteral
products, the total daily patient exposure to aluminum from the admixture
should be considered and maintained at no more than 5 mcg/kg/day [see Use In
Monitoring And Laboratory Tests
Monitor fluid and electrolyte status, serum osmolarity,
blood glucose, liver and kidney function, blood count and coagulation
parameters throughout treatment [see DOSAGE AND ADMINISTRATION].
Use In Specific Populations
Appropriate administration of ELCYS is not expected to
cause major birth defects, miscarriage or adverse maternal or fetal outcomes.
Animal reproduction studies have not been conducted with cysteine
The estimated background risk for major birth defects and
miscarriage for the indicated populations is unknown. All pregnancies have a
background risk of birth defect, loss or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defect and
miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%,
Data available on the effects of cysteine hydrochloride
on infants, either directly or through breastmilk, do not suggest a significant
risk of adverse events from exposure. Although there are no data on the
presence of cysteine hydrochloride in human or animal milk or the effects on
milk production, appropriate administration of ELCYS is not expected to cause
harm to a breastfed infant. The development and health benefits of
breastfeeding should be considered along with the mother's clinical need for
ELCYS and any potential adverse effects on the breastfed infant from ELCYS or
from the underlying maternal condition.
ELCYS is approved for use in pediatric patients, from
birth to 17 years of age, for use as an additive to amino acid solutions to
meet the nutritional requirements of newborn infants, including preterm
infants, requiring total parenteral nutrition (TPN) and pediatric patients with
severe liver disease who may have impaired enzymatic processes and require TPN.
The safety profile for ELCYS use in pediatric patients includes risks of
acid-base imbalance and hyperammonemia.
Acid-base imbalance, including metabolic acidosis, may
occur with ELCYS administration in preterm infants. Frequent clinical and
laboratory assessments are necessary to monitor and manage fluid balance,
electrolyte concentrations, and acid-base balance during parenteral nutrition
therapy [see WARNINGS AND PRECAUTIONS].
Hyperammonemia is of special significance in infants
(birth to two years of age). This reaction appears to be related to a
deficiency of the urea cycle amino acids of genetic or product origin. It is
essential that blood ammonia be measured frequently in infants [see WARNINGS
Because of immature renal function, preterm infants
receiving prolonged PN treatment with ELCYS may be at higher risk of aluminum
toxicity [see WARNINGS AND PRECAUTIONS].
Clinical studies with ELCYS have not been performed to
determine whether patients aged 65 and over respond differently from younger
Monitor patients with impaired renal function receiving
PN solutions containing the recommended dosage of ELCYS with frequent clinical
evaluation and laboratory tests to assess renal function, including serum
electrolytes and fluid balance [see DOSAGE AND ADMINISTRATION, WARNINGS
Monitor patients with impaired liver function receiving
PN solutions containing the recommended dosage of ELCYS with frequent clinical
evaluation and laboratory tests to assess liver function, such as bilirubin and
liver function parameters [see DOSAGE AND ADMINISTRATION, WARNINGS