Included as part of the PRECAUTIONS section.
Risk Of Death In Preterm Infants Due To Pulmonary Lipid
Deaths in preterm infants after infusion of soybean
oil-based intravenous lipid emulsions have been reported in medical literature.
Autopsy findings in these preterm infants included intravascular lipid
accumulation in the lungs. The risk of pulmonary lipid accumulation with
Omegaven is unknown.
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. This risk due to poor lipid clearance
should be considered when administering intravenous lipid emulsions.
Monitor patients receiving Omegaven for signs and
symptoms of pleural or pericardial effusion.
Omegaven contains fish oil and egg phospholipids, which
may cause hypersensitivity reactions. Signs or symptoms of a hypersensitivity
reaction may include: tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia,
hypotension, cyanosis, vomiting, nausea, headache, sweating, dizziness, altered
mentation, flushing, rash, urticaria, erythema, fever, or chills. If a
hypersensitivity reaction occurs, stop infusion of Omegaven immediately and
initiate appropriate treatment and supportive measures [see CONTRAINDICATIONS].
Risk Of Infections
Lipid emulsions, such as Omegaven, can support microbial
growth and are an independent risk factor for the development of bloodstream
infections. The risk of infection is increased in patients with
malnutrition-associated immunosuppression, long-term use and poor maintenance
of intravenous catheters, or immunosuppressive effects of other conditions or
To decrease the risk of infectious complications, ensure
aseptic technique in catheter placement and maintenance, as well as in the
preparation and administration of Omegaven.
Monitor for signs and symptoms of early infections
including fever and chills, laboratory test results that might indicate
infection (including leukocytosis and hyperglycemia), and frequently inspect
the intravenous catheter insertion site for edema, redness, and discharge.
Fat Overload Syndrome
Fat overload syndrome is a rare condition that has been
reported with intravenous lipid emulsions. A reduced or limited ability to
metabolize lipids accompanied by prolonged plasma clearance may result in this
syndrome, which is characterized by a sudden deterioration in the patient's
condition including fever, anemia, leukopenia, thrombocytopenia, coagulation
disorders, hyperlipidemia, hepatomegaly, deteriorating liver function, and
central nervous system manifestations (e.g., coma). The cause of fat overload
syndrome is unclear. 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. The syndrome is
usually reversible when the infusion of the lipid emulsion is stopped.
Administering PN to severely malnourished patients may
result in refeeding syndrome, which is characterized by the intracellular shift
of potassium, phosphorus, and magnesium as the patient becomes anabolic.
Thiamine deficiency and fluid retention may also develop. To prevent these
complications, closely monitor severely malnourished patients and slowly
increase their nutrient intake.
Impaired lipid metabolism with hypertriglyceridemia may
occur in conditions such as inherited lipid disorders, obesity, diabetes
mellitus, and metabolic syndrome. Serum triglyceride levels greater than 1,000
mg/dL have been associated with an increased risk of pancreatitis [see CONTRAINDICATIONS].
To evaluate the patient’s capacity to metabolize and
eliminate the infused lipid emulsion, measure serum triglycerides before the
start of infusion (baseline value), and regularly throughout treatment.
If hypertriglyceridemia (triglycerides greater than 250
mg/dL in neonates and infants or greater than 400 mg/dL in older children)
develops, consider stopping the administration of Omegaven for 4 hours and
obtain a repeat serum triglyceride level. Resume Omegaven based on new result
as indicated [see DOSAGE AND ADMINISTRATION].
Omegaven contains no more than 25 mcg/L of aluminum.
Aluminum may reach toxic levels with prolonged parenteral administration if
kidney function is impaired. Preterm infants are particularly at risk because
their kidneys are immature, and they require large amounts of calcium and
phosphate solutions, which 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
Monitoring And Laboratory Tests
Monitor serum triglycerides [see Hypertriglyceridemia], fluid and electrolyte status, blood glucose, liver and kidney
function, coagulation parameters, and complete blood count including platelets
Essential Fatty Acids
Monitoring patients for laboratory evidence of essential
fatty acid deficiency (EFAD) is recommended. Laboratory tests are available to
determine serum fatty acids levels. Reference values should be consulted to
help determine adequacy of essential fatty acid status. Increasing essential
fatty acid intake (enterally or parenterally) is effective in treating and
Interference With Laboratory Tests
The lipids contained in Omegaven may interfere with some
laboratory blood tests (e.g., hemoglobin, lactate dehydrogenase, bilirubin, and
oxygen saturation) if blood is sampled before lipids have cleared from the
bloodstream. Lipids are normally cleared after a period of 5 to 6 hours once
the lipid infusion is stopped.
Impairment Of Fertility
No studies have been performed
with fish oil triglycerides to evaluate the carcinogenic potential or its
effect on fertility.
Fish oil triglycerides was
negative in the bacterial mutagenicity test with Salmonella typhimurium and
the hypoxanthine phosphoribosyl transferase (HPRT) gene mutation assay in
Chinese hamster V79 cells. Fish oil triglycerides was not clastogenic in
cultured human peripheral lymphocytes or in a rat bone marrow cytogenetic
Use In Specific Populations
There are no available data on Omegaven use in pregnant
women to establish a drug-associated risk of major birth defects, miscarriage,
or adverse maternal or fetal outcomes. Animal reproduction studies have not
been conducted with fish oil triglycerides.
The estimated background risk of major birth defects and
miscarriage in the indicated population is unknown. All pregnancies have a
background risk of birth defect, loss, or other adverse outcomes. In the US
general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%,
No data are available regarding the presence of fish oil
triglycerides from Omegaven in human milk, the effects on the breastfed infant,
or the effects on milk production. Lactating women receiving oral omega-3 fatty
acids have been shown to have higher levels of omega-3 fatty acids in their
milk. The developmental and health benefits of breastfeeding should be
considered along with the mother's clinical need for Omegaven, and any
potential adverse effects of Omegaven on the breastfed infant.
The effectiveness of Omegaven was established in two
open-label clinical trials of 82 pediatric patients, 3 to 42 weeks of age,
including preterm neonates with estimated gestational age of greater than 24
weeks at birth. Patients administered Omegaven attained and maintained growth
through at least 108 weeks of treatment [see Clinical Studies].
The safety of Omegaven was established in 189 pediatric
patients (19 days to 15 years of age). The most common adverse reactions in
Omegaven-treated patients were vomiting, agitation, and bradycardia [see ADVERSE
Deaths in preterm infants after infusion of intravenous
soybean oil-based lipid emulsion have been reported in literature [see WARNINGS
Preterm neonates and infants who receive treatment with
Omegaven may be at risk of aluminum toxicity and other metabolic abnormalities
[see WARNINGS AND PRECAUTIONS].
Clinical trials of Omegaven did not include patients 65
years of age and older.