INTRALIPID

Intralipid ® 10% (A 10% Intravenous Fat Emulsion) is a sterile, non-pyrogenic fat emulsion prepared for intravenous administration as a source of calories and essential fatty acids. It is made up of 10% 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. The soybean oil is a refined natural product consisting of a mixture of neutral triglycerides of predominantly unsaturated fatty acids with the following structure: where are 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. R 3 is primarily either the choline or ethanolamine ester of phosphoric acid. Glycerin is chemically designated C 3 H 8 O 3 and is a clear colorless, hygroscopic syrupy liquid. It has the following structural formula: Intralipid 10% (A 10% Intravenous Fat Emulsion) has an osmolality of approximately 300 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 1.1 kcal per mL of Intralipid 10%. The phospholipids present contribute 47 milligrams or approximately 1.5 mmol of phosphorus per 100 mL of the emulsion. The primary plastic container (Biofine TM ) 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), PVC. The container is nontoxic and biologically inert. This product is not made with natural rubber latex. 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. Figure Figure Figure Figure Figure Figure Figure

Intralipid ® 10% is indicated as 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 as a source of essential fatty acids for prevention of EFAD.

Intralipid 10% should be administered as a part of Intravenous nutrition via peripheral vein or by central venous infusion. Adult Patients The initial rate of infusion in adults should be 1 mL/minute for the first 15 to 30 minutes of infusion. If no untoward reactions occur (see ADVERSE REACTIONS section), the infusion rate can be increased to 2 mL/minute. Not more than 500 mL of Intralipid 10% (A 10% I.V. Fat Emulsion) should be infused into adults on the first day of therapy. If the patient has no untoward reactions, the dose can be increased on the following day. The daily dosage should not exceed 2.5 g of fat/kg of body weight (25 mL of Intralipid 10% per kg). Intralipid 10% should make up no more than 60% of the total caloric input to the patient. Maximum infusion rate should not exceed 0.1 g/kg/hr. Carbohydrate and a source of amino acids should comprise the remaining caloric input. Pediatric Patients The dosage for premature infants starts at 0.5 g fat/kg body weight/24 hours (5 mL Intralipid 10%) and may be increased in relation to the infant's ability to eliminate fat. The maximum recommended dosage is 3 g fat/kg/24 hours. Pediatric patients may be at risk for parenteral nutrition-associated liver disease (PNALD), also known as intestinal failure-associated liver disease (see WARNINGS section) when receiving Intralipid for durations exceeding two weeks. During intravenous administration of Intralipid 10%, perform liver tests to monitor for PNALD. The initial rate of infusion in older pediatric patients should be no more than 0.1 mL/minute for the first 10 to 15 minutes. If no untoward reactions occur, the rate can be changed to permit infusion of 1 mL of Intralipid 10%/kg/hour (equivalent to 0.1 g/kg/hour). The daily dosage should not exceed 3 g of fat/kg of body weight 3 . Intralipid 10% (equivalent to 0.125 g/kg/hour) should make up no more than 60% of the total caloric input to the patient. Carbohydrate and a source of amino acids should comprise the remaining caloric input. Essential Fatty Acid Deficiency When Intralipid 10% (A 10% I.V. Fat Emulsion) is administered to correct essential fatty acid deficiency, eight to ten percent of the caloric input should be supplied by Intralipid 10% in order to provide adequate amounts of linoleic and linolenic acids. When EFAD occurs together with stress, the amount of Intralipid 10% needed to correct the deficiency may be increased. Administration See MIXING GUIDELINES AND LIMITATIONS section for information regarding mixing this fat emulsion with other parenteral fluids. Intralipid 10% can be infused into the same central or peripheral vein as carbohydrate/amino acids solutions by means of a Y-connector near the infusion site. This allows for mixing of the emulsion immediately before entering the vein or for alternation of each parenteral fluid. If infusion pumps are used, flow rates of each parenteral fluid should be controlled with a separate pump. Fat emulsion may also be infused through a separate peripheral site. Use a 1.2 micron filter with Intralipid 10%. Filters of less than 1.2 micron pore size must not be used. Conventional administration sets and TPN pooling bags contain polyvinyl chloride (PVC) components that have DEHP (di(2-ethylhexyl) phthalate) as a plasticizer. Fat‑containing fluids such as Intralipid 10% extract DEHP from these PVC components and it may be advisable to consider infusion of Intralipid 10% through a non-DEHP administration set. Do not use any bag in which there appears to be an oiling out on the surface of the emulsion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit.

Intralipid 10% 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 of Intralipid 10%.

The adverse reactions observed can be separated into two classes: Those more frequently encountered are due: either to contamination of the intravenous catheter and result in sepsis, or to 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 10% (A 10% I.V. Fat Emulsion). Less frequent reactions more directly related to Intralipid 10% 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 10%. The causes and significance of this phenomenon are unknown.

STORAGE Intralipid 10% should not be stored above 25°C (77°F). Do not freeze Intralipid 10%. If accidentally frozen, discard the bag.