Fat Emulsion (Fish Oil and Plant Based)

Dosage Forms

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

Emulsion, Intravenous [preservative free]:

SMOFlipid: 20% (100 mL, 250 mL, 500 mL, 1000 mL) [contains egg phospholipids (egg lecithin)]

Pharmacology

Mechanism of Action

Fat emulsion is metabolized and utilized as an energy source; provides fatty acids (linoleic acid, oleic acid, caprylic acid, palmitic acid, capric acid, stearic 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.

Pharmacokinetics/Pharmacodynamics

Metabolism

Fatty acids, phospholipids, and glycerol are metabolized by cells to adenosine triphosphate (ATP), carbon dioxide, and water

Excretion

Biliary (phospholipids)

Use: Labeled Indications

Caloric/fatty acid source: Source of calories, essential fatty acids, and omega-3 fatty acids for adults requiring parenteral nutrition.

Contraindications

Hypersensitivity to fish, egg, soybean, or any other component of the formulation; severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride concentrations >1,000 mg/dL). Note: Although the manufacturer's labeling lists hypersensitivity to peanut protein as a contraindication, the product does not contain peanut protein. However, a low risk of cross-reactivity between soy and peanuts may exist.

Canadian labeling: Additional contraindications (not in US labeling): Severe hepatic insufficiency; severe blood coagulation disorders; severe renal insufficiency without access to hemofiltration or dialysis; acute shock; acute pulmonary edema; hyperhydration; decompensated cardiac insufficiency; unstable conditions (eg, severe post-traumatic conditions, uncompensated diabetes mellitus, acute MI, CVA, embolism, metabolic acidosis, severe sepsis, hypotonic dehydration)

Dosage and Administration

Dosing: Adult

Caloric/fatty acid source: IV: 1 to 2 g/kg/day; daily dose may be infused over 12 to 24 hours; maximum: 2.5 g/kg/day. Note: Fat emulsion should not exceed 60% of the total daily calories. At the onset of therapy, observe patient for any immediate allergic reactions (eg, dyspnea, cyanosis, fever).

Dosing: Geriatric

Energy expenditure and requirements may be lower in these patients; refer to adult dosing.

Dosing: Pediatric

Parenteral Nutrition: Limited data available:

Infants and Children: IV: Usual reported dose: 2 g/kg/day; reported range: 1.5 to 3.5 g/kg/day with the majority of experience in home parenteral nutrition patients; dosing based on a prospective, randomized, double-blind active controlled trial, and a retrospective cohort comparison. The randomized controlled trial enrolled 28 subjects (age range: 5 months to 11 years) requiring home TPN for ≥4 weeks and randomly assigned them to receive either fish oil-based lipids (active group: n=15) or plant-based lipids (control group: n=13) as part of the PN regimen; fish oil-based lipids were found to be well-tolerated and resulted in a significant decrease in total bilirubin compared to an increased total bilirubin seen in the plant-based lipid group; liver function parameters also trended lower in the active group compared to the control group; the active group also had significantly increased omega-3 fatty acids and alpha-tocopherol concentrations (Goulet 2010). The retrospective study included eight children with elevated total bilirubin secondary to TPN (age: Median: 7.5 months; range: 3 months to 3.2 years) who were changed to fish oil-based lipids and then compared to a similar historic cohort (n=9) who continued receiving standard plant-based lipids; after 6 months of therapy, data showed a significant decrease in the bilirubin in the fish oil-based lipid group compared to the historic cohort which experienced an increase in bilirubin; 62.5% of patients receiving fish oil-based lipids had a complete resolution of jaundice compared to 22% of the cohort group (Muhammed 2012).

Adolescents: Limited data available: IV: Initial: 1 g/kg/day; increase gradually to 2 g/kg/day (SMOFlipid prescribing information [Australia 2016]). Note: US labeling for adults has a maximum daily dose of 2.5 g/kg/day.

Reconstitution

Do not use if discolored (should be homogenous liquid with milky appearance) or if the emulsion contains a precipitate, phase separation, and/or there are leaks in the bag. Inspect the integrity indicator before removing the over pouch; discard the product if the indicator is black. Do not add additives directly to the fat emulsion. When preparing parenteral nutrition admixture, do not add fat emulsion to the TPN container first; destabilization of the lipid emulsion may occur. First transfer dextrose solution to the TPN admixture container; then transfer amino acid injection; then transfer lipid emulsion. Amino acid injection, dextrose injection, and lipid emulsions may be simultaneously transferred to the admixture container; use gentle agitation during admixing to minimize localized concentration effects; may shake bags gently after each addition. Do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP).

Administration

IV: Administer by IV infusion via peripheral line or central venous infusion using DEHP-free administration sets and lines. Initial rate of infusion should be 0.5 mL/minute for the first 15 to 30 minutes; gradually increase until reaching the required rate after 30 minutes as tolerated. Do not exceed a rate of 0.5 mL/kg/hour. May be simultaneously infused with amino acid dextrose mixtures by means of Y-connector located near infusion site (flow rates of each solution should be controlled separately by infusion pumps). When administered with dextrose and amino acids, the choice of a central or peripheral infusion depends on the osmolarity of the final infusate (osmolarity ≥900 mOsm/L must be infused through a central vein). All fat emulsion infusions should be filtered whether part of an admixture or infused separately using a 1.2-micron in-line filter only (ISMP 2016). To prevent air embolism, use a nonvented infusion set or close the vent on a vented set, avoid multiple connections, do not connect flexible bags in series, fully evacuate residual gas in the bag prior to administration, do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off pump before the bag runs dry.

Dietary Considerations

Caloric content: 2 kcal/mL

Phosphorus: 15 mmol/L

Fat emulsion should not exceed 60% of the total daily calories.

Storage

Store at 20°C to 25°C (68°F to 77°F). Store in overpouch until ready for use; once removed from overpouch, use immediately. If not used immediately, the manufacturer suggests storing at 2°C to 8°C (35.6°F to 46.4°F) for no longer than 24 hours; after removal from refrigeration, the emulsion should be infused within 24 hours. Do not freeze. Avoid excessive heat.

Drug Interactions

Vitamin K Antagonists (eg, warfarin): Fat Emulsion (Fish Oil and Plant Based) may diminish the anticoagulant effect of Vitamin K Antagonists. 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

1% to 10%:

Cardiovascular: Hypertension (3%), tachycardia (≤1%), thrombophlebitis (≤1%)

Central nervous system: Dizziness (≤1%), headache (≤1%)

Dermatologic: Pruritus (≤1%), skin rash (≤1%)

Endocrine & metabolic: Hyperglycemia (5%), increased serum triglycerides (3%), increased gamma-glutamyl transferase (≤1%)

Gastrointestinal: Nausea (9%), vomiting (7%), abdominal pain (4%), flatulence (4%), dyspepsia (2%), cholestasis (≤1%), diarrhea (≤1%), dysgeusia (≤1%)

Genitourinary: Urinary tract infection (2%)

Hematologic & oncologic: Anemia (2%), C-reactive protein increased (≤1%), leukocytosis (≤1%)

Hepatic: Abnormal hepatic function tests (≤1%), increased serum alkaline phosphatase (≤1%)

Local: Catheter infection (2%), sepsis (2%)

Respiratory: Dyspnea (≤1%), pneumonia (≤1%)

Miscellaneous: Fever (4%)

<1%, postmarketing, and/or case reports: Infection

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 (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. Consider discontinuation or dose reduction in patients who develop abnormal LFTs.
• Hypersensitivity: Contains soybean oil, fish oil, and egg phospholipids; hypersensitivity reactions may occur. Cross sensitivity has been observed between soybean and peanut. 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 baseline serum triglycerides before initiating therapy, at the time of each dosage increase, and regularly throughout treatment. In adults with triglycerides >400 mg/dL, reduce the dose and monitor triglycerides.
• 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: The use of fat emulsion has been associated with anemia likely due to hemodilution (Zellner 1967). Use with caution in patients with anemia.
• Bleeding disorders: Use with caution in patients with bleeding disorders.
• Fat embolism: Use with caution in patients who may be at danger for fat embolism.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Pancreatitis: Use with caution in patients with pancreatitis without hyperlipidemia.
• Renal impairment: Use with caution in patients with renal impairment; may contain aluminum, which may accumulate following prolonged administration in patients with renal impairment.
• Respiratory disease: Use with caution in patients with respiratory disease.

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:

• Elderly: Energy expenditure and requirements may be lower in elderly patients.
• Pediatric [US Boxed Warning]: Deaths in preterm infants following administration of fat emulsion have been reported; autopsy findings included intravascular fat accumulation in the lungs. Premature infants, low-birth-weight infants, and small-for-gestational-age infants clear intravenous fat emulsion poorly and have increased free fatty acid plasma levels following fat emulsion infusion. The safe and effective use in pediatric patients, including preterm infants, has not been established.

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 a carbohydrate/amino acid solution is recommended to minimize the risk of metabolic acidosis.
• Three-in-one mixtures: Lipid emulsion in a three-in-one mixture may obscure the presence of a precipitate; follow compounding guidelines, especially for calcium and phosphate additions.

Monitoring Parameters

Monitor for signs and symptoms of infection (including vascular access device complications); fluid and electrolyte status; serum osmolarity; blood glucose; blood counts (including platelets and coagulation parameters); signs and symptoms of essential fatty acid deficiency, fat overload, refeeding syndrome, and/or hypersensitivity reactions.

Monitor hepatic and renal function tests periodically. Monitor 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); monitor especially closely in patients with pancreatitis or hepatic disease.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. Severe maternal malnutrition may cause adverse events to the fetus/neonate. Indications for fat emulsion therapy in pregnant women are the same as in nonpregnant women. The ASPEN guidelines for parenteral and enteral nutrition state that intravenous fat emulsion may be used safely in pregnant women to provide calories and prevent essential fatty acid deficiency (ASPEN Guidelines 2002).

Patient Education

What is this drug used for?

• It is used to aid diet needs.
• It is used to give nutrition to the body.

Frequently reported side effects of this drug

• Nausea
• Vomiting

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
• Liver problems like dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes
• Infection
• High blood sugar like 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
• Dizziness
• Passing out
• Blue/gray skin discoloration
• Headache
• Sweating a lot
• Confusion
• Flushing
• Severe loss of strength and energy
• Bruising
• Bleeding
• Injection site swelling, redness, or oozing
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.