Source: FDA, National Drug Code (US) Revision Year: 2020
Use of Omegaven is contraindicated in patients with:
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 (4)].
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.
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 (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)].
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.
Monitor serum triglycerides [see Warnings and Precautions (5.6)], fluid and electrolyte status, blood glucose, liver and kidney function, coagulation parameters, and complete blood count including platelets throughout treatment.
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 preventing EFAD.
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.
The following clinically significant adverse reactions are described elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety database for Omegaven reflects exposure in 189 pediatric patients (19 days to 15 years of age) treated for a median of 14 weeks (3 days to 8 years) in two clinical trials. Omegaven was administered at a maximum dose of 1 g/kg/day as the lipid component of a PN regimen which also included dextrose, amino acids, vitamins, and trace elements; 158 (84%) of these patients received concurrent lipids from enteral nutrition [see Clinical Studies (14)].
Adverse reactions that occurred in more than 5% of patients who received Omegaven and with a higher incidence than the comparator group are shown in Table 1. Patients had a complicated medical and surgical history prior to receiving Omegaven treatment and the mortality was 13%. Underlying clinical conditions prior to the initiation of Omegaven therapy included prematurity, low birth weight, necrotizing enterocolitis, short bowel syndrome, ventilator dependence, coagulopathy, intraventricular hemorrhage, and sepsis.
Table 1. Adverse Reactions in Greater Than 5% of Omegaven-Treated Pediatric Patients with PNAC:
| Adverse Reaction | Omegaven (N=189) n (%) |
|---|---|
| Vomiting | 87 (46) |
| Agitation | 67 (35) |
| Bradycardia | 66 (35) |
| Apnea | 38 (20) |
| Viral Infection | 30 (16) |
| Erythema | 23 (12) |
| Rash | 15 (8) |
| Abscess | 14 (7) |
| Neutropenia | 13 (7) |
| Hypertonia | 11 (6) |
| Incision site erythema | 11 (6) |
Twelve (6%) Omegaven-treated patients were listed for liver transplantation (1 patient was listed 18 days before treatment, and 11 patients after a median of 42 days [range: 2 days to 8 months] of treatment); 9 (5%) received a transplant after a median of 121 days (range: 25 days to 6 months) of treatment, and 3 (2%) were taken off the waiting list because cholestasis resolved.
One hundred thirteen (60%) Omegaven-treated patients reached DBil levels less than 2 mg/dL and AST or ALT levels less than 3 times the upper limit of normal, with median AST and ALT levels for Omegaven-treated patients at 89 and 65 U/L, respectively, by the end of the study.
Median hemoglobin levels and platelet counts for Omegaven-treated patients at baseline were 10.2 g/dL and 173 × 109/L, and by the end of the study these levels were 10.5 g/dL and 217 × 109/L, respectively. Adverse reactions associated with bleeding were experienced by 74 (39%) of Omegaven-treated patients.
Median glucose levels at baseline and the end of the study were 86 and 87 mg/dL for Omegaven-treated patients, respectively. Hyperglycemia was experienced by 13 (7%) Omegaven-treated patients.
Median triglyceride levels at baseline and the end of the study were 121 mg/dL and 72 mg/dL for Omegaven-treated patients respectively. Hypertriglyceridemia was experienced by 5 (3%) Omegaven-treated patients.
The triene:tetraene (Mead acid:arachidonic acid) ratio was used to monitor essential fatty acid status in Omegaven-treated patients only in Study 1 (n=123) [see Warnings and Precautions (5.8)]. The median triene:tetraene ratio was 0.02 (interquartile range: 0.01 to 0.03) at both baseline and the end of the study. Blood samples for analysis may have been drawn while the lipid emulsion was being infused and patients received enteral or oral nutrition.
The following adverse reaction has been identified with use of Omegaven in another country. Because this reaction was reported voluntarily from a population of uncertain size, it is not possible to reliably estimate its frequency or establish a causal relationship to drug exposure.
Life-threatening hemorrhage following a central venous catheter change was reported in a 9-month-old infant with intestinal failure who received PN with Omegaven as the sole lipid source; he had no prior history of bleeding, coagulopathy, or portal hypertension.
Some published studies have demonstrated prolongation of bleeding time in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. The prolongation of bleeding times reported in those studies did not exceed normal limits and there were no clinically significant bleeding episodes. Nonetheless, it is recommended to periodically monitor bleeding time in patients receiving Omegaven and concomitant antiplatelet agents or anticoagulants.
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%, respectively.
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 (14)].
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 Reactions (6.1)].
Deaths in preterm infants after infusion of intravenous soybean oil-based lipid emulsion have been reported in literature [see Warnings and Precautions (5.1)].
Preterm neonates and infants who receive treatment with Omegaven may be at risk of aluminum toxicity and other metabolic abnormalities [see Warnings and Precautions (5.7, 5.8)].
Clinical trials of Omegaven did not include patients 65 years of age and older.
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