Intralipid® 20% (A 20% I.V. Fat Emulsion) is a sterile, non-pyrogenic fat emulsion intended as a source of calories and essential fatty acids for use in a pharmacy admixture program. It is made up of 20% Soybean Oil, 1.2% Egg Yolk Phospholipids, 2.25% Glycerin, and Water for Injection. In addition, sodium hydroxide has been added to adjust the pH so that the final product pH is 8. pH range is 6 to 8.9.

Intralipid 20% Pharmacy Bulk Package is not intended for direct infusion. It is a sterile dosage form which contains several single doses for use in preparation of three-in-one or total nutrient admixtures (TNAs) in a pharmacy admixture program.

The soybean oil is a refined natural product consisting of a mixture of neutral triglycerides of predominantly unsaturated fatty acids with the following structure:

Whereare saturated and unsaturated fatty acid residues.

The major component fatty acids are linoleic acid (44-62%), oleic acid (19-30%), palmitic acid (7-14%), α-linolenic acid (4-11%) and stearic acid (1.4-5.5%)1. These fatty acids have the following chemical and structural formulas:

Purified egg phosphatides are a mixture of naturally occurring phospholipids which are isolated from the egg yolk. These phospholipids have the following general structure:

contain saturated and unsaturated fatty acids that abound in neutral fats. R3 is primarily either the choline or the ethanolamine ester of phosphoric acid.

Glycerin is chemically designated C3H8O3 and is a clear colorless, hygroscopic syrupy liquid. It has the following structural formula:

Intralipid 20% (A 20% I.V. Fat Emulsion) has an osmolality of approximately 350 mOsmol/kg water (which represents 260 mOsmol/L of emulsion) and contains emulsified fat particles of approximately 0.5 micron size.

The total caloric value, including fat, phospholipid and glycerin, is 2.0 kcal per mL of Intralipid 20%. The phospholipids present contribute 47 milligrams or approximately 1.5 mmol of phosphorus per 100 mL of the emulsion.

The primary plastic container (BiofineTM) is made from multilayered film specifically designed for parenteral nutrition drug products. The film is polypropylene based comprising three co-extruded layers. It contains no plasticizers and exhibits virtually no leachables. The container does not contain DEHP (di(2-ethylhexyl) phthalate) or PVC. This product is not made with natural rubber latex. The container is nontoxic and biologically inert.

The container-emulsion unit is a closed system and is not dependent upon entry of external air during administration.

The container is overwrapped to provide protection from the physical environment and to provide an additional moisture barrier when necessary.

Intralipid is metabolized and utilized as a source of energy causing an increase in heat production, decrease in respiratory quotient and increase in oxygen consumption. The infused fat particles are cleared from the blood stream in a manner thought to be comparable to the clearing of chylomicrons.

Intralipid will prevent the biochemical lesions of essential fatty acid deficiency (EFAD) and correct the clinical manifestations of the EFAD syndrome.

Intralipid® 20% Pharmacy Bulk Package is indicated for use in a pharmacy admixture program for the preparation of three-in-one or total nutrition admixtures (TNAs) to provide a source of calories and essential fatty acids for patients requiring parenteral nutrition for extended periods of time (usually for more than 5 days) and a source of essential fatty acids for prevention of EFAD.

Intralipid is contraindicated in patients with:

• Disturbances of normal fat metabolism such as pathologic hyperlipemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipidemia.
• Known hypersensitivity to egg, soybean, peanut protein, or to any of the active ingredients or excipients in Intralipid 20%.

INTRALIPID 20% PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INTRAVENOUS ADMINISTRATION. DILUTING INTRALIPID 20% TO A 10% CONCENTRATION WITH INTRAVENOUS FLUID SUCH AS NORMAL SALINE OR OTHER DILUENTS DOES NOT PRODUCE A DILLITION THAT IS EQUIVALENT IN COMPOSITION TO INTRALIPID 10% I.V. FAT EMULSION, AND SUCH A DILUTION SHOULD NOT BE GIVEN BY DIRECT INTRAVENOUS ADMINISTRATION.

Caution should be exercised in administering of Intralipid 20% (A 20% I.V. Fat Emulsion) to patients with severe liver damage, pulmonary disease, anemia or blood coagulation disorders, or when there is danger of fat embolism as occurs in post traumatic fractures of the pelvis and of long bones.

Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders

Risk of Parenteral Nutrition-Associated Liver Disease

Parenteral nutrition-associated liver disease (PNALD), also referred to as intestinal failure- associated liver disease (IFALD), can present as cholestasis or hepatic steatosis, and may progress to steatohepatitis with fibrosis and cirrhosis (possibly leading to chronic hepatic failure). The etiology of PNALD is multifactorial; however, intravenously administered phytosterols (plant sterols) contained in plant-derived lipid emulsions, including Intralipid, have been associated with development of PNALD.

In a randomized active-controlled, double-blind, parallel-group, multi-center study that included 152 neonates and 9 patients ranging in age from 29 to 153 days who were expected to require PN for at least 28 days, parenteral nutrition-associated cholestasis (PNAC), a precursor to PNALD, developed more frequently in Intralipid-treated patients than in patients treated with a 4-oil mixed lipid emulsion.

PNAC (defined as direct bilirubin >2mg/dl with a second confirmed elevation >2mg/dl at least 7 days later) occurred in 11.5% (9/78) in Intralipid-treated patients and 2.4% (2/83) of patients treated with a 4-oil mixed lipid emulsion. Most PNAC events occurred in patients who were treated for longer than 28 days.

The estimated cumulative incidence of PNAC is shown in the Kaplan-Meier cumulative incidence curve in Figure 1.

Figure 1: Cumulative Incidence Curve of Time to Parenteral Nutrition-Associated Cholestasis (PNAC) with Standard Error Bars

Monitor liver tests in patients treated with Intralipid and consider discontinuation or dosage reduction if abnormalities occur.

Other Hepatobiliary Disorders

Hepatobiliary disorders including cholecystitis and cholelithiasis have developed in some PN-treated patients without preexisting liver disease.

Monitor liver tests when administering Intralipid. Patients developing signs of hepatobiliary disorders should be assessed early to determine whether these conditions are related to Intralipid use.

When Intralipid 20% is administered, the patient's capacity to eliminate the infused fat from the circulation must be monitored by use of an appropriate laboratory determination of serum triglycerides. Overdosage must be avoided.

During intravenous administration with Intralipid 20%, perform liver tests to monitor for PNALD. If patients develop liver test abnormalities, consider discontinuation of Intralipid or dosage reduction. (See WARNINGS section).

Frequent platelet counts should be done in neonatal patients receiving parenteral nutrition with Intralipid.

Drug product contains no more than 25 mcg/L of aluminum.

The adverse reactions observed can be separated into two classes:

1. Those more frequently encountered are due either to a) contamination of the intravenous catheter and result in sepsis, or to b) vein irritation by concurrently infused hypertonic solutions and may result in thrombophlebitis. These adverse reactions are inseparable from the hyperalimentation procedure with or without Intralipid.
2. Less frequent reactions more directly related to Intralipid are: a) immediate or early adverse reactions, each of which has been reported to occur in clinical trials, in an incidence of less than 1%; dyspnea, cyanosis, allergic reactions, hyperlipemia, hypercoagulability, nausea, vomiting, headache, flushing, increase in temperature, sweating, sleepiness, pain in the chest and back, slight pressure over the eyes, dizziness, and irritation at the site of infusion, and, rarely, thrombocytopenia in neonates; b) delayed adverse reactions such as hepatomegaly, jaundice due to central lobular cholestasis, splenomegaly, thrombocytopenia, leukopenia, transient increases in liver tests, and overloading syndrome (focal seizures, fever, leukocytosis, hepatomegaly, splenomegaly and shock).

The deposition of a brown pigmentation in the reticuloendothelial system, the so-called “intravenous fat pigment,” has been reported in patients infused with Intralipid . The causes and significance of this phenomenon are unknown.

In the event of fat overload during therapy, stop the infusion of Intralipid 20% (A 20% I.V. Fat Emulsion) until visual inspection of the plasma, determination of triglyceride concentrations, or measurement of plasma light-scattering activity by nephelometry indicates the lipid has cleared. Re-evaluate the patient and institute appropriate corrective measures. See WARNINGS and PRECAUTIONS.

Intralipid 20% (A 20% I.V. Fat Emulsion) Pharmacy Bulk Package should be administered only as a part of a three-in-one or total nutrient admixture via peripheral vein or by central venous infusion.

Because of the potential for life threatening events, caution should be taken to ensure that precipitates have not formed in any parenteral nutrition mixture.

Perform all manipulations in a suitable work area, such as a laminar flow hood.

Failure to follow the Mixing Guidelines and Limitations below, including recommended storage temperature, storage time, order of mixing, etc., may result in an unstable admixture.

Intralipid 20% (A 20% I.V. Fat Emulsion) may be mixed with Amino Acid and Dextrose Injections where compatibility have been demonstrated. Additives known to be incompatible should not be used. Please consult with pharmacist. If, in the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store solutions containing additives (e.g., Vitamins and Minerals). Protect the admixed PN solution from light.

Protect the admixed PN solution from light.

When being mixed the following proper mixing sequence must be followed to minimize pH related problems by ensuring that typically acidic Dextrose Injections are not mixed with lipid emulsions alone:

1. Transfer Dextrose Injection to the TPN (Total Parenteral Nutrition) Admixture Container
2. Transfer Amino Acid Injection
3. Transfer Intralipid 20%

Note: Amino Acid Injection, Dextrose Injection and Intralipid 20% may be simultaneously transferred to the admixture container using an automatic mixer. Admixing should be accompanied by gentle agitation to avoid localized concentration effects.

Additives must not be added directly to Intralipid 20% (A 20% I.V. Fat Emulsion) Pharmacy Bulk Package and in no case should Intralipid 20% be added to the TPN container first. Bags should be shaken gently after each addition to minimize localized concentration.

If the admixture is not used immediately, the in-use storage time and conditions prior to use are the responsibility of the user and should normally not be longer than 24 hours at 2-8°C. After removal from storage at 2-8°C, the admixture should be infused within 24 hours.

It is essential that the admixture be prepared using strict aseptic techniques as this nutrient mixture is a good growth medium for microorganisms.

Supplemental electrolytes, trace metals or multivitamins may be required in accordance with the prescription of the attending physician.

The prime destabilizers of emulsions are excessive acidity (low pH) and inappropriate electrolyte content. Careful consideration should be given to addition of divalent cations (Ca++ and Mg++) which have been shown to cause emulsion instability. Amino acid solutions exert a buffering effect protecting the emulsion. The admixture should be inspected carefully for “breaking or oiling out” of the emulsion. “Breaking or oiling out” is described as the separation of the emulsion and can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the admixed emulsion. The admixture should also be examined for particulates. The admixture must be discarded if any of the above is observed.

Intralipid 20% is supplied as a sterile emulsion in 1000 mL Pharmacy Bulk Package.

1000 mL NDC 0338-0519-14

Intralipid 20% is also available in the following fill sizes:

100 mL: 0338-0519-58

250 mL: 0338-0519-09

500 mL: 0338 0519-13

Intralipid 20% should not be stored above 25°C (77°F). Do not freeze Intralipid 20%. If accidentally frozen, discard the bag.

1. Padley FB: “Major Vegetable Fats”, The Lipid Handbook (Gunstone FD, Harwood JL, Padley FB, eds.), Chapman and Hall Ltd., Cambridge, UK (1986), pp. 88-9.
2. Levene MI, Wigglesworth JS, Desai R: Pulmonary fat accumulation after Intralipid infusion in the preterm infant. Lancet 1980; 2(8199):815-8.
3. American Academy of Pediatrics: Use of intravenous fat emulsion in pediatric patients. Pediatrics 1981; 68:5(Nov) 738-43.

(Rev May 2022) Manufactured for
Baxter Healthcare Corporation
Deerfield, IL 60015 USA

Manufactured by
Fresenius Kabi,
Uppsala, Sweden

Intralipid® is a registered trademark of Fresenius Kabi AB.

Instruction for Use - Intralipid® 20% Pharmacy Bulk Package Container

PACKAGE LABEL - PRINCIPAL DISPLAY - Intralipid 1000 mL Bag Label

NDC 0338-0519-14

Intralipid ® 20%

A 20% I.V. Fat Emulsion

1000 mL
Pharmacy Bulk Package

Not for Direct Infusion
For Intravenous Use
Rx only