warnings and cautions
5 WARNINGS AND PRECAUTIONS • Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants: Acute respiratory distress, metabolic acidosis, and death after rapid infusion of intravenous lipid emulsions have been reported. ( 5.1 ) • Hypersensitivity Reactions: Monitor for signs or symptoms. Discontinue infusion if reaction occurs. ( 5.2 ) • Risk of Infections, Fat Overload Syndrome, Refeeding Syndrome, and Hypertriglyceridemia : Monitor for signs and symptoms; monitor laboratory parameters. ( 5.3 , 5.4 , 5.5 , 5.6 ) • Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm infants. ( 5.7 ) • Monitoring and Laboratory Tests : Routine laboratory monitoring is recommended, including monitoring for essential fatty acid deficiency. ( 5.8 ) 5.1 Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants In the postmarket setting, serious adverse reactions including acute respiratory distress, metabolic acidosis, and death have been reported in neonates and infants after rapid infusion of intravenous lipid emulsions. Hypertriglyceridemia was commonly reported. Strictly adhere to the recommended total daily dosage; the hourly infusion rate should not exceed 1.5 mL/kg/hour [see Dosage and Administration ( 2.3 )]. 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. Carefully monitor the infant's ability to eliminate the infused lipids from the circulation (e.g., measure serum triglycerides and/or plasma free fatty acid levels). If signs of poor clearance of lipids from the circulation occur, stop the infusion and initiate a medical evaluation [see Warnings and Precautions ( 5.4 , 5.6 ) and Overdosage ( 10 )]. 5.2 Hypersensitivity Reactions Omegaven contains fish oil and egg phospholipids, which may cause hypersensitivity reactions. In postmarketing experience, anaphylaxis has been reported following Omegaven administration [see Adverse Reactions ( 6.2 )] . Omegaven is contraindicated in patients with known hypersensitivity to fish or egg protein or to any of the active or inactive ingredients in Omegaven [see Contraindications ( 4 )] . If a hypersensitivity reaction occurs, stop infusion of Omegaven immediately and initiate appropriate treatment and supportive measures. 5.3 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 concomitant drugs. 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. 5.4 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 formulation was administered according to instructions. The syndrome is usually reversible when the infusion of the lipid emulsion is stopped. 5.5 Refeeding Syndrome 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. 5.6 Hypertriglyceridemia 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 ( 4 )] . 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 ( 2.3 )] . 5.7 Aluminum Toxicity 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 administration. 5.8 Monitoring/Laboratory Tests Routine Monitoring Monitor fluid status closely in patients with pulmonary edema or heart failure. Throughout treatment, monitor serum triglycerides [see Warnings and Precautions ( 5.7 )] , fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count (including platelets), and coagulation parameters. The lipids contained in Omegaven may interfere with the results of some laboratory tests (e.g., hemoglobin, lactate dehydrogenase, bilirubin, oxygen saturation) if the blood is sampled before the lipids have cleared from the bloodstream. Conduct these tests at least 6 hours after stopping the infusion. Omegaven contains Vitamin K that may counteract anticoagulant activity [see Drug Interactions ( 7 )]. Essential Fatty Acids Monitoring patients for signs and symptoms 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 preventing EFAD.