Fat Emulsion (Fish Oil Based)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Emulsion, Intravenous:

Omegaven: 5 g/50 mL (50 mL); 10% (100 mL) [contains egg phospholipids (egg lecithin)]

Pharmacology

Mechanism of Action

Fat emulsion (fish oil based) is metabolized and utilized as an energy source; provides fatty acids (linoleic acid, oleic acid, arachidonic acid, palmitic acid, palmitoleic acid, myristic acid, and alpha linolenic acid) and omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) necessary for normal structure and function of cell membranes.

Use: Labeled Indications

Parenteral nutrition-associated cholestasis (treatment): A source of calories and fatty acids in pediatric patients with parenteral nutrition-associated cholestasis (PNAC).

Limitations of use: Not indicated for the prevention of PNAC.

Contraindications

Hypersensitivity to fish or egg protein or to any component of the formulation; severe hemorrhagic disorders; severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride >1,000 mg/dL)

Dosage and Administration

Dosing: Pediatric

Parenteral nutrition, patients with parenteral nutrition-associated cholestasis (PNAC): Note: Initiate as soon as direct or conjugated bilirubin levels are ≥2 mg/dL in patients who are expected to be parenteral nutrition-dependent for ≥2 weeks. Administer until direct or conjugated bilirubin levels are <2 mg/dL or until the patient no longer requires parenteral nutrition.

Infants, Children, and Adolescents: IV: 1 g/kg/day; if hypertriglyceridemia develops once the infusion has been initiated (serum triglycerides >250 mg/dL in infants or >400 mg/dL in older children), consider discontinuing for 4 hours; resume as indicated based on repeat serum triglyceride level. If triglycerides remain elevated, consider a reduced dose of 0.5 to 0.75 g/kg/day with incremental increase up to 1 g/kg/day; maximum daily dose: 1 g/kg/day.

Dietary Considerations

Caloric content: 1.12 kcal/mL

Storage

Store below 25°C (77°F). Avoid excessive heat; do not freeze; if frozen, discard product. Once the bottle is connected to the infusion set, use immediately; complete infusion within 12 hours when using a Y-connector. Admixtures should also be used immediately or 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.

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Fat Emulsion (Fish Oil Based) may enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Anticoagulants: Fat Emulsion (Fish Oil Based) may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Test Interactions

Elevated plasma lipids may interfere with some laboratory blood tests (eg, hemoglobin, lactate dehydrogenase, bilirubin, oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream. Lipids are normally cleared after 5 to 6 hours once the infusion is stopped.

Adverse Reactions

>10%:

Cardiovascular: Bradycardia (35%)

Central nervous system: Agitation (35%)

Dermatologic: Erythema (12%)

Gastrointestinal: Vomiting (46%)

Hematologic & oncologic: Hemorrhage (39%)

Hepatic: Decreased serum bilirubin (60%)

Infection: Viral infection (16%)

Respiratory: Apnea (20%)

1% to 10%:

Central nervous system: Hypertonia (6%)

Dermatologic: Skin rash (8%), catheter-site erythema (6%)

Endocrine & metabolic: Hyperglycemia (7%), hypertriglyceridemia (3%)

Hematologic & oncologic: Neutropenia (7%)

Infection: Abscess (7%)

Warnings/Precautions

Concerns related to adverse effects:

• Fat overload syndrome: Although rare, a reduced or limited ability to metabolize lipids accompanied by prolonged plasma clearance resulting in a sudden deterioration in the patient's condition accompanied by fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, liver fatty infiltration (hepatomegaly), deteriorating liver function, and CNS manifestations (eg, coma) may occur; usually reversible upon discontinuation.
• Hepatic effects: Although the exact etiology is unknown and likely multifactorial, parenteral nutrition associated liver disease (PNALD) has been reported in patients receiving parenteral nutrition for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis, fibrosis, and cirrhosis, possibly leading to hepatic failure; cholecystitis and cholelithiasis have also been observed.
• Hypersensitivity: Contains fish oil and egg phospholipids; hypersensitivity reactions may occur. Discontinue use immediately if a reaction occurs and treat appropriately.
• Hypertriglyceridemia: Impaired lipid metabolism with hypertriglyceridemia may occur in conditions such as inherited lipid disorders, obesity, diabetes mellitus, and metabolic syndrome. Obtain serum triglycerides before initiating therapy, at the time of each dosage increase, and regularly throughout treatment. In neonates and infants with triglycerides >250 mg/dL and older children with triglycerides >400 mg/dL, consider stopping administration for 4 hours and obtain a repeat serum triglyceride level. Resume therapy based on new result as indicated.
• Refeeding syndrome: Refeeding severely undernourished patients with parenteral nutrition may result in the refeeding syndrome (eg, 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.

Disease-related concerns:

• Anemia: Use with caution in patients with anemia. The use of fat emulsion has been associated with anemia likely due to hemodilution (Zellner 1967).
• Bleeding disorders: Use with caution in patients with bleeding disorders.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; may contain aluminum, which may accumulate following prolonged administration in patients with renal impairment.
• Toxicity secondary to highly lipid soluble substances: Hemodynamic and other instability: Successful resuscitation following the administration of fat emulsion has been reported in animal studies and several human case reports in which cardiovascular toxicity was unresponsive to conventional resuscitation and antidotal measures. Successful resuscitation following the administration of fat emulsion has been reported in pediatric patients (Fuzaylov 2010; Ludot 2008; Shah 2009; Wong 2010). Additional information is available at http://www.lipidrescue.org. Consider use when toxicity secondary to a highly lipid soluble substance is likely and conventional methods are unsuccessful. Continue CPR throughout treatment with lipid emulsion. Consultation with a medical toxicologist or poison control center is highly recommended.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Deaths in preterm infants following IV administration of soybean oil-based fat emulsions have been reported; autopsy findings included intravascular fat accumulation in the lungs. Premature infants and small-for-gestational-age infants clear intravenous fat emulsion poorly and have increased free fatty acid plasma levels following fat emulsion infusion. Monitor patients for signs and symptoms of pleural or pericardial effusion.

Dosage form specific issues:

• Aluminum: May contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal impairment. Premature neonates are at higher risk due to immature renal function and aluminum intake from other parenteral sources. Parenteral aluminum exposure of >4 to 5 mcg/kg/day is associated with CNS and bone toxicity; tissue loading may occur at lower doses (Federal Register 2002). See manufacturer's labeling.

Other warnings/precautions:

• Administration: The too-rapid administration of fat emulsion can cause fluid and/or fat overloading, resulting in dilution of serum electrolyte concentrations, overhydration, congested states, pulmonary edema, impaired pulmonary diffusion capacity, or metabolic acidosis; hourly infusion rate should be as low as possible.
• Appropriate use: Simultaneous infusion of an amino acid solution is recommended to minimize the risk of metabolic acidosis.

Monitoring Parameters

Fluid and electrolyte status, serum osmolarity, blood glucose, blood counts (including platelets and coagulation parameters), hepatic and renal function periodically; triglycerides before initiation of therapy and at least weekly during therapy (or until triglycerides are stable and when changes are made in the amount of fat administered [ASPEN Guidelines 2002]); signs/symptoms of infection (including vascular access device complications), essential fatty acid deficiency, fat overload, refeeding syndrome, pleural or pericardial effusion, and/or hypersensitivity reactions.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of infection, signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), fast breathing, shortness of breath, chest pain, fast heartbeat, slow heartbeat, dizziness, passing out, blue/gray skin discoloration, severe nausea, vomiting, headache, sweating a lot, confusion, agitation, flushing, severe loss of strength and energy, bruising, bleeding, or injection site edema, oozing, or redness (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.