Included as part of the PRECAUTIONS section.
Death In Preterm Infants
Deaths in preterm infants after infusion of intravenous
lipid emulsions have been reported. Autopsy findings included intravascular
lipid accumulation in the lungs.
Base the decision to treat preterm and small for gestational
age infants with intravenous lipid emulsion upon careful benefit-risk
assessment. Strictly adhere to the recommended total daily dose;Â hourly
infusion rate should be as slow as possible and should not exceed 0.75
mL/kg/hour [see DOSAGE AND ADMINISTRATION].
Preterm and small for gestational age infants have poor
clearance of intravenous lipid emulsion and increased free fatty acid plasma
levels following lipid emulsion infusion; therefore, seriously consider
administration of less than the maximum recommended doses in these patients in
order to decrease the likelihood of intravenous fat overload.
Carefully monitor the infant's ability to eliminate the
infused lipids from the circulation (such as serum triglycerides and/or plasma
free fatty acid levels) [see Hypertriglyceridemia].
Because of the risk of thrombocytopenia, monitor platelet
counts frequently in neonatal patients receiving parenteral nutrition with
Stop infusion immediately and treat patient accordingly if
signs or symptoms of a hypersensitivity or allergic reaction develop. Signs or
symptoms may include: tachypnea, dyspnea, hypoxia,Â bronchospasm, tachycardia,
hypotension, cyanosis, vomiting,Â nausea, headache, sweating, dizziness,
altered mentation, flushing,Â rash, urticaria, erythema, pyrexia, and chills.
Patients who require parenteral nutrition are at high risk
of infections due to malnutrition and their underlying disease state.
Infection and sepsis may occur as a result of the use of intravenous catheters
to administer parenteral nutrition, poor maintenance of catheters, or
immunosuppressive effects of illness,Â drugs, and parenteral formulations.
Decrease the risk of septic complications with heightened
emphasis on aseptic technique in catheter placement and maintenance, as well as
aseptic technique in the preparation of the nutritional formula.
Carefully monitor for signs and symptoms (including fever
and chills) of early infections, including laboratory test results (including
leukocytosis and hyperglycemia) and frequent checks of the parenteral access
Fat Overload Syndrome
Fat overload syndrome is a rare condition that has been
reported with intravenous lipid formulations. A reduced or limited ability to
metabolize the lipids contained in Nutrilipid® 20% accompanied by prolonged
plasma clearance may result in a syndrome characterized by a sudden
deterioration in the patient's condition accompanied by fever, anemia,
leukopenia,Â thrombocytopenia, coagulation disorders, hyperlipidemia, liver
fatty infiltration (hepatomegaly), deteriorating liver function, and central
nervous system manifestations (e.g., coma). The cause of the fat overload syndrome
is unclear. The syndrome is usually reversible when the infusion of the lipid
emulsion is stopped. Although it has been most frequently observed when the
recommended lipid dose was exceeded, cases have also been described where the
lipid formulation was administered according to instructions.
Refeeding severely undernourished patients with parenteral
nutrition may result in the refeeding syndrome, characterized by the
intracellular shift of potassium, phosphorus, and magnesium as the patient
becomes anabolic. Thiamine deficiency and fluid retention may also develop.
Carefully monitor severely undernourished patients and slowly increase their
nutrient intakes, while avoiding overfeeding, to prevent these complications.
Monitoring / Laboratory Tests
Monitor fluid status closely in patients with pulmonary
edema or heart failure.
Monitor serum triglycerides [see Hypertriglyceridemia],
fluid and electrolyte status, serum osmolarity, blood glucose,Â liver and
kidney function, blood count (including platelets), and coagulation parameters
Interference With Laboratory Tests
Content of Vitamin K may counteract anticoagulant activity
[see DRUG INTERACTIONS].
The lipids contained in this emulsion may interfere with the
results of certain laboratory tests if the blood sample is taken before the
lipids are eliminated from the serum (these are generally eliminated after a
period of 5 to 6 hours without receiving lipids).
Nutrilipid® 20% contains no more than 25 mcg/L of aluminum.
The aluminum contained in Nutrilipid® 20% may reach toxic levels with prolonged
administration in patients with impaired kidney function. Preterm infants are
at greater risk because their kidneys are immature, and they require large amounts
of calcium and phosphate solutions that contain aluminum.
Patients with impaired kidney function, including preterm
infants, 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 of total parenteral nutrition products.
Risk Of Parenteral Nutrition Associated Liver Disease
Parenteral Nutrition Associated Liver Disease (PNALD) has
been reported in patients who receive parenteral nutrition for extended periods
of time, especially preterm infants, and can present as cholestasis or
steatohepatitis. The exact etiology is unknown and is likely multifactorial.
Intravenously administered phytosterols (plant sterols) contained in
plant-derived lipid formulations have been associated with development of PNALD
although a causal relationship has not been clearly established.
If Nutrilipid® 20% treated patients develop liver test
abnormalities consider discontinuation or dose reduction.
To evaluate the patient's capacity to eliminate and
metabolize the infused lipid emulsion, measure serum triglycerides before the
start of infusion (baseline value), with each increase in dosage, and regularly
Reduce dose of Nutrilipid® 20% and monitor serum
triglyceride levels in patients with serum triglyceride concentrations above
400 mg/dL to avoid the clinical consequences associated with
hypertriglyceridemia. Serum triglyceride levels above 1000 mg/dL have been
associated with an increased risk of pancreatitis.
Impaired lipid metabolism with hypertriglyceridemia may
occur in conditions such as inherited lipid disorders, obesity, diabetes
mellitus, and metabolic syndrome. In these cases, increased triglycerides can
also be increased by glucose and/or overfeeding.Â Monitor overall energy intake
and other sources of fat and glucose,Â as well as drugs that may interfere with
lipid and glucose metabolism.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term animal studies have not been conducted to evaluate
the carcinogenic potential of Nutrilipid® 20%, or its effects on fertility.
Genotoxic studies have not been conducted with Nutrilipid® 20% to assess its
Use In Specific Populations
Pregnancy Category C
There are no adequate or well controlled studies with
Nutrilipid® 20% in pregnant women. Additionally, animal reproduction studies
have not been conducted with Nutrilipid® 20%. It is not known whether
Nutrilipid® 20% can cause fetal harm when administered to a pregnant woman.
Nutrilipid® 20% should be given to a pregnant woman only if clearly needed.
It is not known whether Nutrilipid® 20% is present in human
milk. Because many drugs are present in human milk, caution should be exercised
when Nutrilipid® 20% is administered to a nursing woman.
The evidence for safety and efficacy in pediatric patients
of Nutrilipid® 20% as a source of calories and essential fatty acids for
parenteral nutrition and as a source of essential fatty acids when a deficiency
occurs when oral or enteral nutrition is not possible,Â insufficient, or
contraindicated is derived from the published literature and clinical
experience with similar soybean oil based intravenous lipid emulsions.
Deaths in preterm infants after infusion of intravenous
lipid emulsion have been reported [see WARNINGS AND PRECAUTIONS].
Patients, particularly preterm infants, are at risk for aluminum toxicity [see WARNINGS
AND PRECAUTIONS]. Patients, including pediatric patients, may be at risk
for PNALD [see WARNINGS AND PRECAUTIONS]. In clinical trials of a pure
soybean oil based intravenous lipid emulsion product, thrombocytopenia in
neonates occurred (less than 1%).
Clinical studies of Nutrilipid® 20% did not include
sufficient numbers of subjects aged 65 and over to determine whether they
respond differently from younger subjects. Other reported clinical experience
has not identified differences in responses between the elderly and younger
patients. In general, dose selection for an elderly patient should be cautious,
usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function, and of concomitant
disease or other drug therapy.
Parenteral nutrition should be used with caution in patients
with hepatic impairment. Hepatobiliary disorders are known to develop in some
patients without preexisting liver disease who receive parenteral nutrition,
including cholestasis, hepatic steatosis,Â fibrosis and cirrhosis (parenteral
nutrition associated liver disease),Â possibly leading to hepatic failure.
Cholecystitis and cholelithiasis have also been observed. The etiology of these
disorders is thought to be multifactorial and may differ between patients.
Monitor liver function parameters closely. Patients
developing signs of hepatobiliary disorders should be assessed early by a
clinician knowledgeable in liver diseases in order to identify causative and
contributory factors, and possible therapeutic and prophylactic interventions.