Fat Emulsion (Plant Based)

Dosage Forms

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

Emulsion, Intravenous:

Clinolipid: 20% (100 mL, 250 mL, 500 mL, 1000 mL)

Intralipid: 20% (100 mL, 250 mL, 500 mL, 1000 mL); 30% (500 mL) [contains egg yolk phospholipids, glycerin]

Nutrilipid: 20% (250 mL, 500 mL, 1000 mL) [contains egg yolk phospholipids, glycerin]

Pharmacology

Mechanism of Action

Fat emulsion is metabolized and utilized as an energy source; provides the essential fatty acids, linoleic acid, and alpha linolenic acid necessary for normal structure and function of cell membranes; in local anesthetic toxicity, lipid emulsion probably extracts lipophilic local anesthesia from cardiac muscle

In toxicity secondary to highly lipid soluble substances, exogenous lipids provide an alternative source of binding (Rowlingson 2008), commonly known as the "lipid sink" effect. High lipid partition constant and large volumes of distribution are good predictors of success when using lipid therapy (French 2011). Lipid administration may also affect the heart in a metabolically advantageous way by improving fatty acid transport (Weinberg 2006).

Pharmacokinetics/Pharmacodynamics

Metabolism

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

Excretion

Biliary (phospholipids)

Half-Life Elimination

0.5 to 1 hour

Use: Labeled Indications

Caloric/fatty acid source: Source of calories and essential fatty acids for patients requiring parenteral nutrition for extended periods of time (usually for longer than 5 days) or when oral or enteral nutrition is not possible, insufficient, or contraindicated; to prevent and treat essential fatty acid deficiency (except Clinolipid and Nutrilipid).

Use: Off Label

Serious hemodynamic or other instability secondary to highly lipid soluble substancescyes

Data from a limited number of patients studied and case reports suggest that IV fat emulsion may be beneficial for the treatment of serious hemodynamic or other instability not responsive to standard resuscitation measures (eg, fluids, vasopressors, inotropes) secondary to highly lipid soluble substances including, but not limited to: lipophilic local anesthetics, beta blockers, calcium channel blockers, tricyclic antidepressants, cocaine, benzonatate, bupropion, lamotrigine, quetiapine, and venlafaxine Arora 2013, Carr [727] 2009, Carr [710] 2009, Castanares-Zapatero 2012, Cohen 2009, Dagtekin 2011, Dix 2011, Finn 2009, Foxall 2007, Franxman 2011, French 2011a, Geib 2012, Hillyard 2010, Jakkala-Saibaba 2011, Jovic-Stosic 2011, Kundu 2013, Liang 2011, Litz 2006, Lu 2009, Montiel 2011, Oakes 2009, Rosenblatt 2006, Sirianni 2008, Weinberg 2009, Young 2009. Additional data may be necessary to further define the role of intravenous fat emulsion in this setting.

Based on the American College of Medical Toxicology (ACMT) Position Statement: Guidance for the Use of Intravenous Lipid Emulsion, the American Society of Regional Anesthesia and Pain Medicine (ASRA), and the American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, IV fat emulsion given for hemodynamic or other instability secondary to local anesthetics and other highly lipid soluble substances may be considered when the patient does not respond to standard resuscitation measures (eg, fluids, vasopressors, inotropes) ACMT 2016, AHA [Lavonas 2016], ASRA [Neil 2018]; in patients with any local anesthetic systemic toxicity event judged to be potentially serious, lipid emulsion should be administered soon after airway management ASRA [Neil 2018].

Contraindications

Intralipid 20%, 30%: Disturbances in normal fat metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if accompanied by hyperlipidemia; pharmacy bulk package is not intended for direct IV administration

Clinolipid, Nutrilipid: Known hypersensitivity to egg or soybean proteins or to any component of the formulation; severe hyperlipidemia (serum triglyceride concentrations above 1,000 mg/dL) or severe disorders of lipid metabolism characterized by hypertriglyceridemia

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to egg, soya or peanut protein or to any component of the formulation; acute shock; severe hyperlipidemia; conditions characterized by severely disordered fat metabolism (eg, severe hepatic impairment, acute MI, hemophagocytotic syndrome, shock)

Dosage and Administration

Dosing: Adult

Note: At the onset of therapy, the patient should be observed for any immediate allergic reactions (eg, dyspnea, cyanosis, and fever).

Caloric source: IV: Note: Fat emulsion should not exceed 60% of the total daily calories.

Initial dose: 1 to 1.5 g/kg/day (not to exceed 500 mL Intralipid 10% or 20% or 330 mL Intralipid 30% [over 4 to 6 hours] on the first day of therapy); daily dose may be infused over 12 to 24 hours; maximum daily dose: 2.5 g/kg/day

Essential fatty acid deficiency (EFAD), prevention: IV: Administer at least 2% to 4% of total caloric intake as linoleic acid and 0.25% to 0.5% as alpha linolenic acid (Mirtallo 2004; Mirtallo 2010)

Essential fatty acid deficiency (EFAD), treatment: Intralipid: IV: Administer 8% to 10% of total caloric intake as fat emulsion; may infuse up to once daily (Riella 1975). If EFAD occurs with stress, the dosage needed to correct EFAD may be increased.

Serious hemodynamic or other instability secondary to highly lipid soluble substances (off-label use): Note: Continue chest compressions during administration (lipid must circulate): 20%: IV: 1.5 mL/kg (maximum: 100 mL; ASRA [Neal 2018]) administered over 1 to 3 minutes, followed immediately by an infusion of 0.25 mL/kg/minute (maximum: 200 to 250 mL; ASRA [Neal 2018]) (recommended infusion durations vary; see below); may repeat the bolus as necessary for persistent cardiovascular collapse or if instability re-emerges (ACMT 2016; AHA [Lavonas 2015]; ASRA [Neal 2018]). Some suggest dosing based on lean body weight (AHA [Lavonas 2015]; ASRA [Neal 2018]). Suggested maximum dose: 10 to 12 mL/kg over the first 30 to 60 minutes (AHA [Lavonas 2015]; ASRA [Neal 2018]).

After administration of the initial bolus and continuous infusion, recommendations regarding the continuous infusion vary significantly:

American College of Medical Toxicology: If after the bolus and continuing the infusion for 3 minutes the patient demonstrates a significant response, the infusion rate may be reduced to 0.025 mL/kg/minute (ie, one-tenth the initial rate). If instability re-emerges, the infusion rate may be increased back to 0.25 mL/kg/minute or the bolus may be repeated (ACMT 2016).

American Heart Association recommendations: Continue infusion for 30 to 60 minutes (AHA [Lavonas 2015]).

American Society of Regional Anesthesia and Pain Medicine: Continue infusion for at least 10 minutes after hemodynamic stability has been restored. Consider rebolus or increase the infusion rate to 0.5 mL/kg/minute if hemodynamic instability persists or recurs. (ASRA [Neal 2018])

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Parenteral nutrition: Intralipid, Nutrilipid: Note: Fat emulsion should not exceed 60% of the total daily calories. At the onset of therapy, the patient should be observed for any immediate allergic reactions such as dyspnea, cyanosis, and fever.

Infants: IV: Initial dose: 0.5 to 1 g/kg/day; increase by 0.5 to 1 g/kg/day to a maximum of 2.5 to 3 g/kg/day depending upon the needs/nutritional goals (ASPEN [Corkins 2015]).

Children 1 to 10 years: IV: Initial dose: 1 to 2 g/kg/day; increase by 0.5 to 1 g/kg/day to a maximum of 2 to 2.5 g/kg/day depending upon the needs/nutritional goals (ASPEN [Corkins 2015]).

Children ≥11 years and Adolescents: IV: Initial dose: 1 g/kg/day, not to exceed 500 mL 20% fat emulsion on the first day of therapy; increase by 1 g/kg/day to a maximum of 1 to 2 g/kg/day (ASPEN [Corkins 2015]).

Essential fatty acid deficiency, prevention: Intralipid: Infants, Children, and Adolescents: IV: Administer 8% to 10% of total caloric intake as fat emulsion; infuse 2 to 3 times weekly; may need to increase dose during stress.

Serious hemodynamic or other instability secondary to highly lipid soluble substances (including, but not limited to, local anesthetics, calcium channel blockers, tricyclic antidepressants, bupropion, lamotrigine, and quetiapine): Note: Use is reserved for patients not responsive to standard resuscitation measures.

Infants, Children, and Adolescents: Very limited data available, optimal dose not defined: 20% fat emulsion: IV: 1.5 mL/kg bolus over 2 to 3 minutes followed immediately by a continuous IV infusion at 0.25 mL/kg/minute; assess response after 3 minutes of infusion. If the patient demonstrates a significant response, the infusion rate may be reduced to 0.025 mL/kg/minute (ie, one-tenth the initial rate). If instability re-emerges, the infusion rate may be increased to 0.25 mL/kg/minute or the 1.5 mL/kg bolus may be repeated (ACMT 2017). Suggested maximum dose: 10 to 12.5 mL/kg (ACMT 2017; Fettiplace 2015).

Reconstitution

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 when other solutions (eg, dextrose) are added. Minimize pH-related problems by ensuring that dextrose solutions, which are typically acidic, are not mixed with lipid emulsions alone. 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 only via peripheral line or by central venous infusion. 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). At the onset of therapy, the patient should be observed for any immediate allergic reactions such as dyspnea, cyanosis, and fever. Change tubing after each infusion. May be simultaneously infused with carbohydrate/amino acid solutions by means of Y-connector located near infusion site or administered in total nutrient mixtures (3-in-1) with amino acids, dextrose, and other nutrients. Fat emulsions of 30% should only be administered in total nutrient mixtures (3-in-1) with amino acids, dextrose, and other nutrients. Hang fat emulsion higher than other fluids (has low specific gravity and could run up into other lines).

Clinolipid: Prior to opening the overwrap of Clinolipid, check the color of the oxygen indicator and compare to the reference color next to the OK symbol. If the color of the oxygen absorber/indicator does not correspond to the reference color, do not use. After opening the bag, use the contents immediately and do not store for a subsequent infusion. Do not connect flexible bags in series to avoid air embolism due to possible residual gas contained in the primary bag. Do not use vented administration sets with vent in the open position to avoid air embolism. When preparing total parenteral nutrition admixture, do not use the EXACTAMIX Inlet H938173 with an EXACTAMIX compounder to transfer Clinolipid injection; EXACTAMIX Inlet H938174 is recommended.

Intralipid: Prior to opening the overwrap, the integrity indicator should be inspected. If the indicator is black, the overwrap is damaged; do not use.

Nutrilipid: To avoid air embolism, use a nonvented infusion set or close the air vent on a vented set and use a dedicated line without any connections. Prior to opening the overwrap, the oxygen indicator should be inspected; if the indicator is pink or dark pink, do not use. May be infused concurrently into the same vein as carbohydrate-amino acid solutions by means of a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps. Do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). See prescribing information for detailed administration information.

Caloric source/EFAD: Initiate infusions of 10% emulsions at 1 mL/minute for 15 to 30 minutes; if no untoward effects occur, the infusion rate may be increased to 2 mL/minute. Initiate infusions of 20% emulsions at 0.5 mL/minute for 15 to 30 minutes; if no untoward effects occur, the infusion rate may be increased to 1 mL/minute.

Serious hemodynamic or other instability secondary to highly lipid soluble substances (off-label use): Administer initial bolus over 1 to 3 minutes followed by a continuous infusion. Chest compressions should continue during administration if patient is in cardiac arrest. Some experts recommend a decreased infusion rate in patients who respond favorably to the initial bolus and infusion (ACMT 2016); repeat bolus or an increase in the infusion rate may be considered if instability persists or recurs. (ACMT 2016; AHA [Lavonas 2015]; ASRA [Neal 2018]).

Dietary Considerations

Phosphorus: ~1.5 mMol /100 mL of emulsion

Caloric content: 10% fat emulsion = 1.1 kcal/mL; 20% fat emulsion = 2 kcal/mL; 30% fat emulsion = 3 kcal/mL

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

Storage

Do not freeze. If accidentally frozen, discard. Do not store partly used containers; fat emulsion can support the growth of various organisms. Do not use if the emulsion appears to be oiling out. Once the closure is penetrated, the contents should be used as soon as possible; the transfer of contents to suitable TPN admixture containers must be completed within 4 hours of closure penetration. Admixtures prepared using fat emulsion should be used promptly or stored under refrigeration at 2°C to 8°C (36°F to 46°F) for 24 hours or less and used completely within 24 hours after removal from refrigeration.

Intralipid, Nutrilipid: Store below 25°C (77°F).

Clinolipid: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). Avoid excessive heat. Store in overpouch until ready to use.

Adverse Reactions

1% to 10%:

Endocrine and metabolic: Hyperlipidemia (≤10%), hyperglycemia (2% to 10%)

Gastrointestinal: Nausea (≤10%), vomiting (≤10%)

Hematologic & oncologic: Hypoproteinemia (2% to 10%)

Hepatic: Abnormal hepatic function tests (2% to 10%)

Frequency not defined:

Cardiovascular: Thrombophlebitis

Gastrointestinal: Cholestasis (central lobular), melanosis (brown fat pigmentation in the reticuloendothelial system)

Genitourinary: Urinary tract infection

Hematologic & oncologic: Leukopenia, splenomegaly, thrombocytopenia

Hepatic: Fat overload syndrome, hepatomegaly, increased liver enzymes

Infection: Septicemia

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Back pain, chest pain, cyanosis, decreased INR, diaphoresis, diarrhea, dizziness, drowsiness, dyspnea, flushing, headache, hypercoagulability state, hypersensitivity reaction, increased body temperature, infusion site irritation, pruritus, pulmonary embolism (fat), sensation of eye pressure

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) can occur; usually reversible upon discontinuation.
• Hepatic effects: Parenteral nutrition: 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: Allergic reactions (eg, tachypnea, dyspnea, hypoxia, bronchospasm, tachycardia, vomiting, headache, sweating) to lipid emulsion may occur; discontinue infusion immediately if signs or symptoms of hypersensitivity or allergic reactions occur.
• Refeeding syndrome: Parenteral nutrition: 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; ensure triglyceride levels remain <400 mg/dL.
• Respiratory disease: Use with caution in patients with respiratory disease.
• Renal impairment: Use with caution; some formulations may contain aluminum, which may accumulate following prolonged administration in renally impaired patients.
• 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). 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: [US Boxed Warning]: Deaths in preterm infants after infusion of IV lipid emulsions have been reported in the medical literature. Autopsy findings included intravascular fat accumulation in the lungs. Preterm infants and low birth weight infants have poor clearance of IV lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. To avoid hyperlipidemia and/or fat deposition, do not exceed recommended daily doses and consider administering less than the maximum recommended doses in preterm and small for gestational age infants. Clinolipid is not indicated for use in pediatric patients. Pediatric clinical studies did not establish that Clinolipid provides sufficient amounts of essential fatty acids (EFA) in pediatric patients, which may predispose them to neurologic complications due to EFA insufficiency. Because free fatty acids displace bilirubin from albumin binding sites, the use of lipid infusions in jaundiced or premature infants should be done with caution.

Dosage form specific issues:

• Aluminum: The parenteral product may contain aluminum; toxic aluminum concentrations may be seen with high doses, prolonged use, or renal dysfunction. 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.
• 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, refeeding syndrome, and/or hypersensitivity reactions.

Monitor liver and renal function tests periodically. Monitor triglycerides before initiation of lipid 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 premature infants, septic infants, and patients with pancreatitis or liver disease.

Pregnancy

Pregnancy Considerations

Animal reproduction studies have not been conducted. 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). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (AHA [Jeejeebhoy 2015]). Lipid emulsion therapy has been used successfully in the resuscitation of a pregnant female with suspected bupivacaine toxicity (Dun-Chi Lin 2017; Spence 2007).

Patient Education

What is this drug used for?

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

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

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
• 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
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
• Severe nausea
• Severe vomiting
• Shortness of breath
• Chest pain
• Dizziness
• Passing out
• Blue/gray skin discoloration
• Fast heartbeat
• Headache
• Sweating a lot
• Severe loss of strength and energy
• Bruising
• Bleeding
• Severe injection site irritation
• 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.