Liposyn III

Sepsis due to contamination of administration equipment and thrombophlebitis due to vein irritation from concurrently administered hypertonic solutions have been encountered. These are attributable to I.V. therapy in general or to the type of infusion administered.

Adverse reactions directly related to fat emulsions are of two types: (1) immediate (acute) and (2) long term (chronic). In studies of lipid products in general, the following immediate reactions have been noted: Allergic reactions, hyperlipemia, dyspnea, cyanosis, flushing, dizziness, headache, sleepiness, nausea, vomiting, hyperthermia, sweating, chest and back pain, thrombocytopenia (rarely in neonates), hypercoagulability and transient increases in liver enzymes.

The following reactions have been noted with long-term therapy with lipid infusions in general: Hepatomegaly, jaundice due to central lobular cholestasis, splenomegaly, thrombocytopenia, leucopenia, transient increases in liver function tests, overloading syndrome and the deposition of brown pigment ("fat pigment") in the reticuloendothelial tissue of the liver. The significance of this last occurrence and its cause are unknown.

Liposyn III is part of the drug classes:

• Enema

• Other drugs for constipation

Liposyn III (Intravenous Fat Emulsion) is a sterile, nonpyrogenic fat emulsion for intravenous administration. It is supplied in both a 10% and 20% concentration.

Liposyn III 10% contains 10% soybean oil, up to 1.2% egg phosphatides added as an emulsifier and 2.5% glycerin in water for injection. Sodium hydroxide has been added for pH adjustment. pH 8.3 (6.0 to 9.0). Liposyn III 10% has an osmolarity of 284 mOsmol/L (approx.) and a specific gravity of 0.995. The total caloric value of Liposyn III 10% including fat, phospholipid and glycerol is 1.1 kcal/mL. Of this total, approximately 0.5 kcal/mL is supplied by linoleic acid.

Liposyn III 20% contains 20% soybean oil, 1.2% egg phosphatides and 2.5% glycerin in water for injection. Sodium hydroxide has been added for pH adjustment. pH 8.3 (6.0 to 9.0). Liposyn III 20% has an osmolarity of 292 mOsmol/L (approx.) and a specific gravity of 0.988. The total caloric value of Liposyn III 20% including fat, phospholipid and glycerol is 2.0 kcal/mL. Of this total, approximately 1.0 kcal/mL is supplied by linoleic acid.

Both Liposyn III 10% and Liposyn III 20% contain emulsified fat particles of approximately 0.4 micron in diameter, similar to naturally occurring chylomicrons.

Soybean Oil, USP is a mixture of neutral triglycerides with the following structure:

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

Glycerin, USP is chemically designated C3H803 and is a clear, colorless, hygroscopic syrupy liquid. It has the following structural formula:

Liposyn III (intravenous fat emulsion) provides the patient requiring parenteral nutrition with a source of calories and the essential fatty acids normally obtained from a nutritionally complete oral diet. The supplemental polyunsaturated fat prevents biochemical changes of essential fatty acid deficiency (EFAD) and prevents and reverses EFAD clinical manifestations (e.g., scaliness of skin, growth retardation, poor wound healing and sparse hair growth).

The infused fat particles are cleared from the bloodstream in a manner thought to be similar to the clearing of chylomicrons. Following infusion, there is a transient increase in plasma triglycerides. The triglycerides are hydrolyzed to free fatty acids and glycerol by the enzyme, lipoprotein lipase. The free fatty acids either enter the tissues (where they may be oxidized or resynthesized into triglycerides and stored) or circulate in the plasma, bound to albumin. In the liver, circulating free fatty acids are oxidized or converted to very low density lipoproteins that re-enter the bloodstream.

Phosphatides are the hydrophobic components of membranes and provide electrically insulated layers. They are involved in the formation of membrane structures. Choline prevents the deposition of fat in the liver.

Glycerol is metabolized to carbon dioxide and glycogen or is used in the synthesis of body fats.

The administration of Liposyn III (intravenous fat emulsion) is contraindicated in patients demonstrating disturbances in normal fat metabolism such as pathologic hyperlipemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipemia.

With the exception of heparin at 1 to 2 units/mL of fat emulsion, additives to the Liposyn III bottle are contraindicated.

Partly used containers must not be stored for later use. Filters must not be used with Liposyn III. Do not use any bottle in which there appears to be an oiling out of the emulsion.

In the event of fat overload during therapy, stop the infusion of Liposyn III 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.

Liposyn III (intravenous fat emulsion) 10% and 20% is a white to slightly off-white emulsion with no evidence of oiling out of the emulsion.

Liposyn III 10% (List No. 9790) is supplied in 200, 250 and 500 mL single-dose containers. Liposyn III 20% (List No. 9791) is supplied in 200, 250 and 500 mL single-dose containers.

Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing.