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Fish Oil Triglycerides Injection





Fish oil triglycerides is a sterile, nonpyrogenic, white, homogenous emulsion for intravenous infusion as a supply of calories in patients with PNAC. Each mL of fish oil triglycerides contains 0.1 g of fish oil, 0.012 g egg phospholipids, 0.025 g glycerin, 0.15 to 0.3 mg dl-alpha-tocopherol, 0.3 mg sodium oleate, water for injection, and sodium hydroxide for pH adjustment (pH 6 to 9). The phosphate content is 0.015 mmol/mL.

The fish oil included in fish oil triglycerides is a triglyceride mixture consisting of esters of long-chain saturated fatty acids and unsaturated fatty acids with the following structure:

Empirical formula: C4H3 - Molecular weight: 130.08 g/mol

where , , and are long chain acyl groups.

Because triglycerides often contain different long chain fatty acids at each position, possible structures can have molecular weights ranging from 700 to 1000 g/mol. The main fatty acid components of the fish oil in fish oil triglycerides are EPA (13% to 26%) and DHA (14% to 27%). The fish oil also contains palmitic acid (4% to 12%), oleic acid (4% to 11%), palmitoleic acid (4% to 10%), myristic acid (2% to 7%), and arachidonic acid (0.2% to 2.0%). Additionally, the mean contents of linoleic acid and alpha linolenic acid are 1.5% and 1.1%, respectively. The fish oil component has a total omega-3 fatty acid content of 40% to 54%. The empirical formula, molecular weight, and chemical structure of the main fatty acid components are:

Fish oil triglycerides 5 mg/50 mL contains 5 grams of fish oil and 0.6 g egg phospholipids, 1.25 g glycerin, 7.5 to 15 mg dl-alpha-tocopherol, 0.015 g sodium oleate, water for injection, and sodium hydroxide for pH adjustment (pH 6 to 9) packaged in a single-dose 50-mL glass bottle enclosed with a rubber stopper. The phosphate content of the drug product is 0.75 mmol.

The mean content of the two major fatty acid components in 50 mL are 1.0 g EPA (range: 0.6 to 1.5 g) and 0.96 g DHA (range: 0.7 to 1.7 g). Additionally, the mean content of linoleic acid, alpha-linolenic acid, and arachidonic acid per 50 mL are 0.16 g, 0.07 g, and 0.13 g, respectively.

Fish oil triglycerides 10 mg/100 mL contains 10 grams of fish oil and 1.2 g egg phospholipids, 2.5 g glycerin, 15 to 30 mg dl-alpha-tocopherol, 0.03 g sodium oleate, water for injection, and sodium hydroxide for pH adjustment (pH 6 to 9) packaged in a single-dose 100-mL glass bottle enclosed with rubber stopper. The phosphate content of the drug product is 1.5 mmol. The mean content of the two major fatty acid components in 100 mL are 2.0 g EPA (range: 1.2 to 3.0 g) and 1.9 g DHA (range: 1.3 to 3.3 g). Additionally, the mean content of linoleic acid, alpha-linolenic acid, and arachidonic acid per 100 mL are 0.31g, 0.13 g, and 0.25 g; respectively.

The total energy content of fish oil triglycerides is 112 kcal/100 mL (1.12 kcal/mL), including lipids, phospholipids, and glycerol.

Fish oil triglycerides has an osmolality of approximately 342 mOsm/kg water (which represents an osmolarity of 273 mOsm/L).

Fish oil triglycerides contains no more than 25 mcg/L of aluminum.


Fish oil triglycerides is indicated as a source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC).

Limitations of Use:

• Fish oil triglycerides is not indicated for the prevention of PNAC. It has not been demonstrated that fish oil triglycerides prevents PNAC in parenteral nutrition (PN)-dependent patients [see Clinical Studies].

• It has not been demonstrated that the clinical outcomes observed in patients treated with fish oil triglycerides are a result of the omega-6:omega-3 fatty acid ratio of the product [see Clinical Studies].


3.1 Administration Instructions

• Fish oil triglycerides can be administered alone or as part of a PN admixture.

• Fish oil triglycerides is for central or peripheral intravenous infusion. When administered with dextrose and amino acids, the choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsm/L or greater must be infused through a central vein.

• Use a 1.2 micron in-line filter during administration.

• Use a dedicated line for PN. Fish oil triglycerides should be infused concurrently into the same vein as dextrose-amino acid solutions (as part of PN) by a Y-connector located closest to the infusion site; flow rates of each solution should be controlled separately by infusion pumps. Avoid multiple connections; do not connect multiple medications in series. Turn off the pump before the bottle runs dry.

• Use a vented infusion set when fish oil triglycerides is infused from the bottle.

• Do not use infusion sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Infusion sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer.

• Prior to infusion, visually inspect fish oil triglycerides for particulate matter and discoloration. Discard the bottle if any particulates or discoloration are observed.

• Gently invert the bottle before use. Use fish oil triglycerides only if the emulsion is homogeneous and the container is undamaged.

• Strict aseptic techniques must be followed.

• Hang the bottle using the attached hanger and start infusion.

• After connecting the infusion set, start infusion of fish oil triglycerides immediately. Complete the infusion within 12 hours when using a Y-connector and within 24 hours when used as part of an admixture.

• For single use only. Discard unused portion.

3.2 Admixing Instructions

If fish oil triglycerides is administered as part of a PN admixture, follow the instructions below.

• Prepare the admixture in PN containers using strict aseptic techniques to avoid microbial contamination.

• Do not add fish oil triglycerides directly to the empty PN container; destabilization of the lipid emulsion may occur.

• When fish oil triglycerides is administered with other infusion solutions (e.g., amino acids, dextrose), the compatibility of the solutions used must be ensured. Questions related to compatibility may be directed to Fresenius Kabi USA, LLC, at 1-800-551-7176.

• The following proper mixing sequence must be followed to minimize pH-related problems by ensuring that typically acidic dextrose solutions are not mixed with lipid emulsions alone:

1. Transfer dextrose solution to the PN container.

2. Transfer amino acid solution to the PN container.

3. Transfer fish oil triglycerides to the PN container.

Simultaneous transfer of amino acid solution, dextrose solution, and fish oil triglycerides using an automated compounding device is also permitted; follow automated compounding device instructions as indicated.

Use gentle agitation during admixing to minimize localized concentration effects; shake container gently after each addition.

• The prime destabilizers of emulsions are excessive acidity (such as a pH less than 5) and inappropriate electrolyte content. Care should be taken if adding divalent cations (e.g., Ca++ and Mg++), which have been shown to cause emulsion instability. Amino acid solutions exert buffering effects that can protect the emulsion from destabilization.

• Inspect the admixture to ensure that precipitates have not formed during preparation of the admixture and the emulsion has not separated. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixture. Discard the admixture if any of these are observed.

• The remaining contents of a partly used PN container must be discarded.

• Start infusion of admixtures containing fish oil triglycerides immediately. If not used immediately, admixtures may be stored for up to 6 hours at room temperature or up to 24 hours under refrigeration. Complete the infusion within 24 hours after removal from storage.

• Follow the instructions of each product included in the admixture.

3.3 Dosing Information

Dosing Considerations

• Prior to administration of fish oil triglycerides, correct severe fluid and electrolyte disorders and measure serum triglycerides to establish a baseline level.

• Initiate fish oil triglycerides dosing as soon as direct or conjugated bilirubin (DBil) levels are 2 mg/dL or greater in pediatric patients who are expected to be PN-dependent for at least 2 weeks.

• The dosing of fish oil triglycerides depends on each patient’s energy requirements, which may be influenced by age, body weight, tolerance, clinical status, and ability to metabolize and eliminate lipids.

• When determining dose, take into account the energy supplied by dextrose and amino acids from PN, as well as energy from oral or enteral nutrition. Energy provided from lipid-based medications must also be taken into account (e.g., propofol).

• Fish oil triglycerides contains 0.15 to 0.30 mg/mL of dl-alpha-tocopherol. Take into account the amount of alpha-tocopherol in fish oil triglycerides when determining the need for additional supplementation of vitamin E.

Recommended Pediatric Dosing

• The recommended fish oil triglycerides dosage for pediatric patients is 1 g/kg/day; this is also the maximum daily dose.

• The initial rate of infusion should not exceed 0.05 mL/minute for the first 15 to 30 minutes of infusion. If tolerated, gradually increase until reaching the required rate after 30 minutes. The maximum infusion rate should not exceed 1.5 mL/kg/hour, corresponding to 0.15 g/kg/hour.

• If hypertriglyceridemia (triglycerides greater than 250 mg/dL in neonates and infants or greater than 400 mg/dL in older children) develops once fish oil triglycerides has been initiated at the recommended dosage, consider stopping the administration of fish oil triglycerides for 4 hours and obtain a repeat serum triglyceride level. Resume fish oil triglycerides based on new result as indicated.

• In patients with elevated triglyceride levels, consider other reasons for hypertriglyceridemia (e.g., renal disease, other drugs). If triglycerides remain at elevated levels, consider a reduced dose of 0.5 g to 0.75 g/kg/day with an incremental increase to 1 g/kg/day.

• Monitor triglyceride levels during treatment [see Warnings and Precautions (5.6, 5.8)].

• The recommended duration for infusion of fish oil triglycerides is between 8 and 24 hours, depending on the clinical situation.

• Administer fish oil triglycerides until DBil levels are less than 2 mg/dL or until the patient no longer requires PN.


Use of fish oil triglycerides is contraindicated in patients with:

• Known hypersensitivity to fish or egg protein or to any of the active ingredients or excipients [see Warnings and Precautions (5.2)].

• Severe hemorrhagic disorders due to a potential effect on platelet aggregation.

• Severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentrations greater than 1,000 mg/dL) [see Warnings and Precautions (5.6)].


5.1 Risk of Death in Preterm Infants due to Pulmonary Lipid Accumulation

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 fish oil triglycerides 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 fish oil triglycerides for signs and symptoms of pleural or pericardial effusion.

5.2 Hypersensitivity Reactions

Fish oil triglycerides 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 fish oil triglycerides immediately and initiate appropriate treatment and supportive measures [see Contraindications (4)].

5.3 Risk of Infections

Lipid emulsions, such as fish oil triglycerides, 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 fish oil triglycerides.

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 lipid 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 fish oil triglycerides for 4 hours and obtain a repeat serum triglyceride level. Resume fish oil triglycerides based on new result as indicated [see Dosage and Administration (3.3)].

5.7 Aluminum Toxicity

Fish oil triglycerides 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 and Laboratory Tests

Routine Monitoring

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.

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 preventing EFAD.

5.9 Interference with Laboratory Tests

The lipids contained in fish oil triglycerides 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:

• Risk of death in preterm infants due to pulmonary lipid accumulation [see Warnings and Precautions (5.1)]

• Hypersensitivity reactions [see Warnings and Precautions (5.2)]

• Risk of infections [see Warnings and Precautions (5.3)]

• Fat overload syndrome [see Warnings and Precautions (5.4)]

• Refeeding syndrome [see Warnings and Precautions (5.5)]

• Hypertriglyceridemia [see Warnings and Precautions (5.6)]

• Aluminum toxicity [see Warnings and Precautions (5.7)]

6.1 Clinical Trials Experience

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 fish oil triglycerides 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. Fish oil triglycerides 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].

Adverse reactions that occurred in more than 5% of patients who received fish oil triglycerides 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 fish oil triglycerides treatment and the mortality was 13%. Underlying clinical conditions prior to the initiation of fish oil triglycerides 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 Fish Oil Triglycerides-Treated Pediatric Patients with PNAC

Twelve (6%) fish oil triglycerides-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%) fish oil triglycerides-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 fish oil triglycerides-treated patients at 89 and 65 U/L, respectively, by the end of the study.

Median hemoglobin levels and platelet counts for fish oil triglycerides-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 fish oil triglycerides-treated patients.

Median glucose levels at baseline and the end of the study were 86 and 87 mg/dL for fish oil triglycerides-treated patients, respectively. Hyperglycemia was experienced by 13 (7%) fish oil triglycerides-treated patients.

Median triglyceride levels at baseline and the end of the study were 121 mg/dL and 72 mg/dL for fish oil triglycerides-treated patients respectively. Hypertriglyceridemia was experienced by 5 (3%) fish oil triglycerides-treated patients.

The triene:tetraene (Mead acid:arachidonic acid) ratio was used to monitor essential fatty acid status in fish oil triglycerides-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.

6.2 Postmarketing Experience

The following adverse reaction has been identified with use of fish oil triglycerides 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 fish oil triglycerides as the sole lipid source; he had no prior history of bleeding, coagulopathy, or portal hypertension.


7.1 Antiplatelet Agents and Anticoagulants

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 fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.


8.1 Pregnancy

Risk Summary

There are no available data on fish oil triglycerides 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.

8.2 Lactation

Risk Summary

No data are available regarding the presence of fish oil triglycerides from fish oil triglycerides 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 fish oil triglycerides, and any potential adverse effects of fish oil triglycerides on the breastfed infant.

8.4 Pediatric Use

The effectiveness of fish oil triglycerides 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 fish oil triglycerides attained and maintained growth through at least 108 weeks of treatment [see Clinical Studies].

The safety of fish oil triglycerides was established in 189 pediatric patients (19 days to 15 years of age). The most common adverse reactions in fish oil triglycerides-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 fish oil triglycerides may be at risk of aluminum toxicity and other metabolic abnormalities [see Warnings and Precautions (5.7, 5.8)].

8.5 Geriatric Use

Clinical trials of fish oil triglycerides did not include patients 65 years of age and older.


In the event of an overdose, fat overload syndrome may occur [see Warnings and Precautions (5.4)]. Stop the infusion of fish oil triglycerides until triglyceride levels have normalized and any symptoms have abated. The effects are usually reversible by stopping the lipid infusion. If medically appropriate, further intervention may be indicated. Lipids are not dialyzable from serum.


Fish oil triglycerides provides a biologically utilizable source of calories and essential fatty acids.

Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation. Fatty acids are also important for membrane structure and function, as precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression.


The plasma concentrations of EPA and DHA, the major fatty acids in fish oil triglycerides, as well as linoleic acid and alpha-linolenic acid (essential fatty acids) were measured along with the markers of essential fatty acid status in 58 pediatric patients with PNAC after an intravenous infusion of 1 mg/kg/day of fish oil triglycerides over 10 weeks. Five patients received fish oil triglycerides as the exclusive lipid source, and all others received concurrent enteral or oral nutrition.

Figure 1: Mean Plasma Concentrations of Fatty Acids Over 10 Weeks of Fish Oil Triglycerides Infusion in Pediatric Patients with PNAC

Error bars represent ± 1 standard deviation (SD).

Numbers at the top of plots represent the number of patients at each time point

If more than one value was available for a patient at any given time point, the average was used.


How Supplied:

Omegaven (fish oil triglycerides) injectable emulsion, 5 g/50 mL and 10 g/100 mL (0.1 g/mL) is a white, homogenous, sterile emulsion supplied as follows:

50 mL single-dose glass bottle NDC 63323-205-21 Carton of 10 x 50 mL NDC 63323-205-50

100 mL single-dose glass bottle NDC 63323-205-31 Carton of 10 x 100 mL NDC 63323-205-00

The stopper used as the bottle closure is not made with natural rubber latex, PVC, or DEHP.

Storage and Handling:

Store below 25°C (77°F). Avoid excessive heat. Do not freeze. If accidentally frozen, discard product.

Once the bottle is connected to the infusion set, use Omegaven immediately. Complete infusion within 12 hours when using a Y-connector [see Dosage and Administration (3.1)].

Infuse admixtures containing Omegaven immediately. If not used immediately, admixtures can be stored for up to 6 hours at room temperature or up to 24 hours under refrigeration. Complete the infusion within 24 hours after removal from storage [see Dosage and Administration (3.2)].

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Rev 07/18