Intralipid 10%

INTRALIPID® 10% (10% i.v fat emulsion) (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:

- ARE SATURATED AND UNSATURATED FATTY ACID RESIDUES.

THE MAJOR COMPONENT FATTY ACIDS ARE LINOLEIC (44-62%), OLEIC (19-30%), PALMITIC (7-14%), LINOLENIC (4-11%) AND STEARIC (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 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® 10% (10% i.v fat emulsion) (A 10% INTRAVENOUS FAT EMULSION) HAS AN OSMOLALITY OF APPROXIMATELY 300 MOSMOL/KG WATER (WHICH REPRESENTS 260 MOSMOL/LITER 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% (10% i.v fat emulsion) . THE PHOSPHOLIPIDS PRESENT CONTRIBUTE 47 MILLIGRAMS OR APPROXIMATELY 1.5 MMOL OF PHOSPHORUS PER 100 ML, OF THE EMULSION.

THE PRIMARY CONTAINER IS MANUFACTURED FROM EXCEL®FILM, A POLYPROPYLENE BASED MATERIAL COMPRISED OF THREE CO-EXTRUDED LAYERS.

THE PLASTIC CONTAINER IS MADE FROM MULTILAYERED FILM SPECIFICALLY DESIGNED FOR PARENTERAL DRUGS. IT CONTAINS NO PLASTICIZERS AND EXHIBITS VIRTUALLY NO LEACHABLES. THE SOLUTION CONTACT LAYER IS A RUBBERIZED COPOLYMER OF ETHYLENE AND PROPYLENE. THE CONTAINER IS NONTOXIC AND BIOLOGICALLY INERT. THE CONTAINER-SOLUTION 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.

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.

THE ADVERSE REACTIONS OBSERVED CAN BE SEPARATED INTO TWO CLASSES:

1. 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 HYPER-ALIMENTATION PROCEDURE WITH OR WITHOUT INTRALIPID® 10% (A 10% I.V. FAT EMULSION).
2. LESS FREQUENT REACTIONS MORE DIRECTLY RELATED TO INTRALIPID® 10% (10% i.v fat emulsion) 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, FLUSH-ING, 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 FUNCTION TESTS, AND OVERLOADING SYNDROME (FOCAL SEIZURES, FEVER, LEUKOCYTOSIS, HEPATOMEGALY, SPLENOMEGALY AND SHOCK).

THE DEPOSITION OF A BROWN PIGMENTATION IN THE RETICULOEN-DOTHELIAL SYSTEM, THE SO-CALLED “INTRAVENOUS FAT PIGMENT,” HAS BEEN REPORTED IN PATIENTS INFUSED WITH INTRALIPID® 10% (10% i.v fat emulsion) . THE CAUSES AND SIGNIFICANCE OF THIS PHENOMENON ARE UNKNOWN.

DEATHS IN PRETERM INFANTS AFTER INFUSION OF INTRAVENOUS FAT EMULSION HAVE BEEN REPORTED IN THE MEDICAL LITERATURE.2 AUTOPSY FINDINGS INCLUDED INTRAVASCULAR FAT ACCUMULATION IN THE LUNGS. TREATMENT OF PREMATURE AND LOW BIRTH WEIGHT INFANTS WITH INTRAVENOUS FAT EMULSION MUST BE BASED UPON CAREFUL BENEFIT-RISK ASSESSMENT.

STRICT ADHERENCE TO THE RECOMMENDED TOTAL DAILY DOSE IS MANDATORY; HOURLY INFUSION RATE SHOULD BE AS SLOW AS POSSIBLE IN EACH CASE AND FAT SHOULD NOT IN ANY CASE EXCEED 1 G FAT/KG IN FOUR HOURS. PREMATURE AND SMALL FOR GESTATIONAL AGE INFANTS HAVE POOR CLEARANCE OF INTRAVENOUS FAT EMULSION AND INCREASED FREE FATTY ACID PLASMA LEVELS FOLLOWING FAT EMULSION INFUSION; THEREFORE, SERIOUS CONSIDERATION MUST BE GIVEN TO ADMINISTRATION OF LESS THAN THE MAXIMUM RECOMMENDED DOSES IN THESE PATIENTS IN ORDER TO DECREASE THE LIKELIHOOD OF INTRAVENOUS FAT OVERLOAD. THE INFANT’S ABILITY TO ELIMINATE THE INFUSED FAT FROM THE CIRCULATION MUST BE CAREFULLY MONITORED (SUCH AS SERUM TRIGLYCERIDES AND/OR PLASMA FREE FATTY ACID LEVELS). THE.LIPEMIA MUST CLEAR BETWEEN DAILY INFUSIONS.

CAUTION SHOULD BE EXERCISED IN ADMINISTERING INTRALIPID® 10% (10% i.v fat emulsion) (A 10% INTRAVENOUS FAT EMULSION) TO PATIENTS WITH SEVERE LIVER DAMAGE, PULMONARY DISEASE, ANEMIA OR BLOOD COAGULATION DISORDERS, OR WHEN THERE IS DANGER OF FAT EMBOLISM.

WARNING: THIS PRODUCT CONTAINS ALUMINUM THAT MAY BE TOXIC. ALUMINUM MAY REACH TOXIC LEVELS WITH PROLONGED PARENTERAL ADMINISTRATION IF KIDNEY FUNCTION IS IMPAIRED. PREMATURE NEONATES ARE PARTICULARLY AT RISK BECAUSE THEIR KIDNEYS ARE IMMATURE, AND THEY REQUIRE LARGE AMOUNTS OF CALCIUM AND PHOSPHATE SOLUTIONS, WHICH CONTAIN ALUMINUM.

RESEARCH INDICATES THAT PATIENTS WITH IMPAIRED KIDNEY FUNCTION, INCLUDING PREMATURE NEONATES, WHO RECEIVE PARENTERAL LEVELS OF ALUMINUM AT GREATER THAN 4 TO 5 MCG/KG/DAY ACCUMULATE ALUMINUM AT LEVELS ASSOCIATED WITH CENTRAL NERVOUS SYSTEM AND BONE TOXICITY. TISSUE LOADING MAY OCCUR AT EVEN LOWER RATES OF ADMINISTRATION.

IN THE EVENT OF FAT OVERLOAD DURING THERAPY, STOP THE INFUSION OF INTRALIPID® 10% 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.