Fat Emulsions (Systemic)


VA CLASSIFICATION
Primary: TN300



Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Nutritional supplement (fatty acid)—

Indications

Accepted

Fatty acid deficiency (prophylaxis and treatment)—Intravenous fat emulsions are used to prevent or reverse fatty acid deficiency and provide a source of calories for patients requiring parenteral nutrition. {01} {02}

—Deficiency of essential fatty acids may lead to anemia, {54} desquamative dermatitis, {54} growth retardation in infants, {53} {54} hepatic dysfunction, {53} {54} impaired wound healing, {54} loss of hair, {54} and thrombocytopenia. {53} {54}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Infused fat particles cause a transient increase in plasma triglyceride concentrations. The triglycerides are then hydrolyzed to free fatty acids and glycerol by the enzyme lipoprotein lipase. The free fatty acids either enter the tissues (to be oxidized or resynthesized to triglycerides for storage) or circulate bound to albumin in the plasma, and subsequently may undergo hepatic oxidation or conversion to very low–density lipoproteins (VLDL) that re-enter the bloodstream. {01} {03}


Other actions/effects:

Fat emulsions also contain phosphatides (a component of which is choline) as an emulsifier, and glycerin to adjust tonicity. {01} {03} Phosphatides are involved in the formation of membrane structures; choline prevents deposition of fat in the liver; and glycerin is metabolized to carbon dioxide and glycogen or is used in the synthesis of fats. {01} {03}

Protein binding:

Bound to albumin. {01}

Biotransformation:

Hepatic. {01}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to eggs, {03} {17} soybeans, {21} or legumes {21} may be sensitive to fat emulsions.

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. It is not known if fat emulsions can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. {01}

Adequate and well-controlled studies have not been done in animals.

FDA Pregnancy Category C. {01}

Breast-feeding

It is not known whether fat emulsions are distributed into human breast milk. However, problems in humans have not been documented.

Pediatrics

Fat emulsions must be administered to preterm infants with extreme caution. These infants have poor clearance of intravenous fat emulsions. The resultant increase of free fatty acid plasma concentrations may lead to fat accumulation in the lungs and possibly death. {01} {04} {05} {15}


Geriatrics


Appropriate studies on the relationship of age to the effects of fat emulsions have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Colorimetric laboratory analysis    (serum lipids may interfere with colorimetric laboratory analysis; blood samples should be drawn in the morning prior to infusion of fat emulsions {18} {19})

With physiology/laboratory test values
Alkaline phosphatase, serum and
Bilirubin, serum and
Cholesterol, serum and{01}{08}
Phospholipid, serum and{08}
Transaminase, serum and
Triglyceride, plasma{01}{08}    (concentrations may be increased {18})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Anemia    (condition may be exacerbated {01} {11})


Blood coagulation disorders or{01}{17}
» Conditions in which there is a disturbance in normal fat metabolism, such as:
Diabetes, uncompensated or{18}{19}{26}
Hyperlipidemia, pathologic or{01}{07}{08}{13}{16}{17}
Lipid nephrosis or{01}{17}
Pancreatitis, acute, if accompanied by hyperlipemia or{01}{06}{17}
Renal insufficiency{18}    (fat emulsions may increase serum lipids and exacerbate these conditions {01})


Hepatic damage, severe{01}    (fat emulsions undergo biotransformation in the liver)


Immunocompromised patient    (fat emulsions have been reported to alter the immune response {47} {48})


Jaundice    (fat emulsions increase free fatty acids, which may displace bilirubin bound to albumin {01} {09})


Platelet dysfunction disorders{10}{11}    (fat emulsions have been reported to cause hypercoagulability)


Pulmonary disease{01}{14}{15}{16}{24}{25}    (fat emulsions may exacerbate condition; slowing infusion rate has been found to reduce pulmonary problems {18} {19} {25})


Sensitivity to fat emulsions
Sepsis    (fat emulsions have been found to alter the immune response and decrease reticuloendothelial system function, which could exacerbate the condition {49} {50} {51} {52})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood coagulation tests and
Hemogram and
Platelet counts    (determinations may be required at weekly intervals, especially during continuous therapy {01} {10} {11} {17})


Bilirubin concentrations, serum and{17}{18}{20}{56}
Cholesterol concentrations, serum and{01}{08}{46}
Hepatic function determinations and{01}{12}{17}{18}
Phospholipid concentrations, serum and{08}{46}
Triglyceride concentrations, plasma{01}{08}{46}    (determinations may be required at weekly intervals, especially in premature infants, to prevent hyperlipemia {15})




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Sepsis{01}{23} (chills, fever, or sore throat)

Incidence rare
    
Allergic reactions, specifically chills{01}{17}{18}{19}
dyspnea, (difficulty in breathing){01}{19}{21}, fever{01}{17}{18}{19}
or urticaria (hives){03}{21}
    
hematologic abnormalities, specifically anemia (unusual tiredness or weakness){01}{19}, hypercoagulability{01}{35}
or thrombocytopenia (unusual bleeding or bruising)—more frequent with prolonged use{01}{11}{19}
    
hyperlipemia (fever; headache; unusual irritability)—more frequent with prolonged use{01}{19}
    
jaundice (yellow eyes or skin)—more frequent with prolonged use{01}
    
pulmonary effects, specifically chest or back pain{01}{17}{19} , or cyanosis (bluish color of skin){01}{17}{19}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Thrombophlebitis (redness, swelling, or pain at injection site){01}{27}

Incidence less frequent
    
Diarrhea {57}{58}{59}
    
dizziness {01}
    
flushing {01}
    
nausea and vomiting {01}





Overdose
For more information on the management of overdose or unintentional ingestion contact a Poison Control Center (see Poison Control Center Listing) .

Treatment of overdose
Discontinue therapy. {01} {19}

Plasma lipid clearance should be determined before restarting therapy. {01} {19}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Fat Emulsions (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to eggs, legumes, soybeans, or fat emulsions





Use in children—May cause or worsen lung problems or jaundice in premature infants

Other medical problems, especially problems with lipid metabolism

Proper use of this medication

» Proper dosing

» Proper storage

Precautions while using this medication
Importance of close monitoring by physician

Importance of reporting any infections to physician


Side/adverse effects
Signs of potential side effects, especially allergic reactions, hematologic abnormalities, hyperlipemia, jaundice, pulmonary effects, and sepsis


General Dosing Information
Although the manufacturer does not recommend the use of a filter during administration of fat emulsions, {01} {18} 1.2-micron filters are used in practice by some clinicians. {28} {29} Filters smaller than 1.2 microns may filter out lipids, or disrupt the stability of the emulsion. {55}

Fat emulsions extract small amounts of plasticizer from PVC containers. {28} {29}

Fat emulsions can be infused into the same central or peripheral vein as amino acids by use of a Y-type infusion set, which allows mixing of the 2 just before they enter the vein. {01} {28}

The combination of parenteral amino acids, dextrose, and fat emulsions in one container (known as 3-in-1, or total nutrient admixture [TNA]) is stable for short periods of time, usually 24 hours, depending on the formulation. {01} {28} {29} {32} {33} {34} The compatibility of electrolytes, vitamins, trace metals, and a few drugs has been evaluated in some combinations, but the stability depends on the formulation used. {29} {33} The order of mixing, final pH, and cation content are {55} important; product information should be consulted. {29}

The addition of 1 or 2 units of heparin per mL to fat emulsions may result in a more rapid clearance of lipemia, {01} {35} {36} {37} {38} may minimize the risks associated with hypercoagulability, {35} and may prevent catheter thrombosis; {46} however, its use is generally not recommended by most clinicians. {56}


Parenteral Dosage Forms

FAT EMULSIONS INJECTION

Usual adult and adolescent dose
Nutritional supplement
Intravenous, 0.5 mL of 20% fat emulsions per minute or 1 mL of 10% fat emulsions per minute for the first fifteen to thirty minutes with the rate then increased to allow no more than 500 mL of the 10% fat emulsions or 250 mL of the 20% fat emulsions to be infused over a period of four to six hours. {01} {28}


Note: Fat emulsions should be administered via peripheral vein or central venous catheter. {01}


Usual adult prescribing limits
The daily dose of fat emulsions should not exceed 3 grams per kilogram of body weight. {01}

Usual pediatric dose
Nutritional supplement
Intravenous, 0.1 mL of 10% or 20% fat emulsions per minute for the first fifteen minutes with the rate then increased to allow no more than 100 mL of 10% fat emulsions per hour or 50 mL of the 20% fat emulsions per hour. {01} {28}


Note: Fat emulsions should be administered via peripheral vein or central venous catheter. A syringe pump unit is used to control administration rates for infants who require small volumes of fat emulsions. {01}


Usual pediatric prescribing limits
The daily dose of fat emulsions should not exceed 4 grams per kilogram of body weight. {01}

Strength(s) usually available
U.S.—

Table 1. Strengths Usually Available



    Safflower
Oil
Soybean
Oil
Fatty Acid Component (%)
Egg
Phospholipid
(%)
Glycerin
(%)
Calories
per mL
Osmolarity
(mOsm)
per Liter
pH
Linoleic
Acid
Oleic
Acid
Palmitic
Acid
Linolenic
Acid
Stearic
Acid
Intralipid                         
  10% [U.S.] (Rx)
  10
50
26
10
9
3.5
1.2
2.25
1.1
260
6–8.9
  10% [Canada](Rx)
  10
50
26.5
10.5
8.5
3.5
1.2
2.25
1.1
300
8
  20% [U.S.] (Rx)
  20
50
26
10
9
3.5
1.2
2.25
2
260
6–8.9
  20% [Canada] (Rx)
  20
50
26.5
10.5
8.5
3.5
1.2
2.25
2
350
8
Liposyn II                Up to:
       
  10% [U.S.] (Rx)
5
5
65.8
17.7
8.8
4.2
3.4

1.2
2.5
1.1
276
8
  10% [Canada] (Rx)
5
5
65.8
17.7
8.8
4.2
3.4
0.7
2.5
1.1
276
8.3
  20% [U.S.] (Rx)
10
10
65.8
17.7
8.8
4.2
3.4
1.2
2.5
1.1
258
8.3
  20% [Canada] (Rx)
10
10
65.8
17.7
8.8
4.2
3.4
1.2
2.5
2
258
8.3
Liposyn III                         
  10% [U.S.] (Rx)
  10
54.5
22.4
10.5
8.3
4.2
1.2
2.5
1.1
284
8.3
  20% [U.S.] (Rx)
  20
54.5
22.4
10.5
8.3
4.2
1.2
2.5
2
292
8.3

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Stability:
Fat emulsions have been shown to support bacterial and fungal growth; {28} {30} {31} visual changes in the emulsion were not noted. {28} {31} The addition of fat emulsions to total parenteral nutrition (TPN) solutions has been found to enhance the ability of these solutions to support bacterial growth. {55} {60}

Incompatibilities:
Depending on the product used, the concentration, the temperature, and the length of mixing time, albumin, amikacin, aminophylline, ampicillin, calcium salts, cephalothin, gentamicin, iron dextran, magnesium chloride, methicillin, penicillin, phenytoin, potassium chloride, tetracycline, tobramycin, and vitamin B complex have been found to be physically incompatible with fat emulsions when mixed directly with the emulsion. {28} {29} Amikacin, methyldopate, and tetracycline have been found to be physically incompatible with Y-site injection. {28} {29} Consult the medical literature for additional information.



Developed: 04/13/1993
Revised: 09/02/1999



References
  1. Liposyn II product information (Abbott—US) Rev 8/89, Rec 1/93.
  1. Cochran E, et al. Parenteral nutrition in pediatric patients. Clin Pharm Vol 7, 5/88, p 352-66.
  1. Olin B, editor. Facts and Comparison Inc. St Louis, MO 1989.
  1. Levene M, et al. Pulmonary fat accumulation after Intralipid infusion in the preterm infant. Lancet 1980; 8199: 815-8.
  1. Boxed warning on IV fat emulsions. FDA Drug Bulletin 3/81.
  1. Gossum A, et al. Lipid-associated total parenteral nutrition in patients with severe acute pancreatitis. JPEN 1988; 12: 250-5.
  1. Cooke R, Burckhart G. Hypertriglyceridemia during the intravenous infusion of a safflower oil-based fat emulsion. J of Pediatr 1983; 103[6]: 959-61.
  1. Carpenter Y, Thonnart N. Parameters for evaluation of lipid metabolism. JPEN 1987; 11[5]: 104S-108S.
  1. Brans Y, et al. Influence of intravenous fat emulsion on serum bilirubin in very low birthweight neonates. Arch Dis Child 1987; 62[2]: 156-60.
  1. Campbell A, et al. Bleeding disorder from the ``Fat Overload'' syndrome. JPEN 1984; 8: 447-9.
  1. Goulet O, et al. Hematologic disorders following prolonged use of intravenous fat emulsions in children. JPEN 1986; 10: 284-8.
  1. McGrath, et al. Intralipid induces hemolysis. Br J of Haematol 1982; 50[2]: 376-8.
  1. Young L, Koda-Kimble M. Applied Therapeutics. 4th ed, 1988.
  1. Adverse cardiopulmonary effects of IV fat emulsions. Reactions 1981 May, p 8-12.
  1. Dahms B, Halpin T. Pulmonary arterial lipid deposit in newborn infants receiving intravenous lipid infusion. J Pediatr 1980; 97[5]: 800-5.
  1. Pereira G, et al. Decreased oxygenation and hyperlipemia during intravenous fat emulsions in premature infants. Pediatr 1980; 66[1]: 26-30.
  1. Pelham L. Rational use of intravenous fat emulsions. Am J Hosp Pharm. 1981; 38: 198-208.
  1. Intralipid 10% and 20% product information (Baxter—Canada) CPS, 1990.
  1. Liposyn II 10% and 20% product information (Abbott—Canada) CPS, 1990.
  1. Andreq G, et al. Lipid metabolism in the neonate. J Pediatr 1976; 88[2]: 279-84.
  1. Hiyama D, et al. Hypersensitivity following lipid emulsion infusion in an adult patient JPEN. 1989; 13[3]: 318-20.
  1. Driscoll D, Blackburn G. Total parenteral nutrition. Drugs. 1990; 40[3]: 346-63.
  1. Freeman J, et al. Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units. NEJM 1990; 323[5]: 301-8.
  1. Venus B, et al. Pulmonary effects of lipid infusion in patients with acute respiratory failure. Crit Care Med 1984; 12[3]: 293.
  1. Hwang T, et al. Effects of intravenous fat emulsion on respiratory failure. Chest 1990; 97: 934-8.
  1. Wicklmayr M, et al. Comparison of metabolic clearance rates of MCT/LCT and LCT emulsions in diabetics. JPEN 1988; 12[1]: 68-71.
  1. Hatton J, et al. Safety and efficacy of a lipid emulsion containing medium-chain triglycerides. Clin Pharm 1990; 9: 366-71.
  1. Trissel L. Handbook on injectable drugs. 5th ed. pp 288-97.
  1. Wells P. An update on lipid compatibility issues. 3/89.
  1. Kim C, et al. Bacterial and fungal growth in intravenous fat emulsions. Am J Hosp Pharm 1983; 40: 1650-3.
  1. Keammerer D. Microbial growth patterns in intravenous fat emulsions. Am J Hosp Pharm 1983; 40: 2159-61.
  1. Driscoll D. Clinical issues regarding the use of total nutrient admixtures. DICP 1990; 24: 296-303.
  1. Allen L. TPN admixtures. U.S. Pharmacist 1990 Jun: 56-9.
  1. Vasilakis A, Apelgren K. Answering the fat emulsion contamination question: three in one admixture vs conventional total parenteral nutrition in a clinical setting. JPEN 1988; 12[4]: 356-9.
  1. Somani P, et al. Safflower oil emulsion: single and multiple infusions with or without added heparin in normal human volunteers. JPEN 1980; 4[3]: 307-11.
  1. Persson E, et al. Plasma clearance of fat emulsion during continuous heparin infusion. Acta Anaesthesiol Scand 1987; 31: 189-92.
  1. Benderly A, et al. Effect of heparin on lipoprotein profile during parenteral fat infusions. JPEN 1983; 7[1]: 37-9.
  1. Committee on Nutrition, Am Academy of Pediatrics. Use of intravenous fat emulsions in pediatric patients. Pediatrics 1981; 68[5]: 738-43.
  1. Intralipid 10% product information (Clintec Nutrition—US), Rev 8/91, Rec 2/92.
  1. Intralipid 20% product information (Clintec Nutrition—US), Rev 8/91, Rec 12/92.
  1. Liposyn III product information (Abbott—US), Rev 6/89.
  1. Liposyn II 10%, 20% (Abbott—Canada) 1992 CPS.
  1. Intralipid 10%, 20% (Clinitec—Canada) 1992 CPS.
  1. To be reused at a later date.
  1. To be reused at a later date.
  1. Meguid M, et al. Short-term effects of fat emulsion on serum lipids in post-operative patients. JPEN 1989; 13[1]: 77-80.
  1. Sax H. Practicalities of lipids: ICU patient, autoimmune disease, and vascular disease. JPEN 1990; 14[5]: 223S-225S.
  1. Cheney C, et al. Association of intravenous lipid emulsion with risk of infection. J Am Coll Nutr 1990; 9[5]: 532.
  1. Burch K, Helms R. Rational use of intravenous fat emulsions. U.S. Pharmacist 1984; 2/84 1984 Feb; H1-7, H-60.
  1. Fischer G, et al. Diminished bacterial defences with Intralipid. Lancet 1980 Oct; p 819-20.
  1. Wan J. Invited comment: lipids and the development of immune dysfunction and infection. JPEN 1988; 12[6]: 43S-52S.
  1. Seidner D, et al. Effects of long-chain triglyceride emulsions on reticuloendothelial system function in humans. JPEN 1989; 13[6]: 614-9.
  1. Roesner M, Grant J. Intravenous lipid emulsions. Nutr in Clin Pract 1987, pp 96-107.
  1. AHFS, 1990, pp 1389-90.
  1. Panelist comment, 1991 revision cycle.
  1. Panel consensus, 1991 revision cycle.
  1. Panelist comment, 1991 revision cycle.
  1. Faintuch J, et al. Diarrhea associated with Intralipid Infusion. JPEN 1981; 5[4]: 325.
  1. Connon J. Diarrhea possibly caused by total parenteral nutrition. N Eng J Med 1979; 301[5]: 273-4.
  1. Scheckelhoff D, et al. Growth of bacteria and fungi in total nutrient admixtures. Am J Hosp Pharm 1986; 43: 73-7.
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