FDA label beb4f755-7fb0-4c82-b486-16135006ea4b

Pharmacy Bulk Package − Not for Direct Infusion.

Deaths in preterm infants after infusion of intravenous fat emulsions have been reported in the medical literature. 1,2 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 should not in any case exceed 1 g/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 infused fat from the circulation must be carefully monitored (such as triglyceride and/or plasma free fatty acid levels). The lipemia must clear between daily infusions.

WARNINGS Deaths in preterm infants after infusion of intravenous fat emulsions have been reported in the medical literature. 1,2 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 should not in any case exceed 1 g/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 infused fat from the circulation must be carefully monitored (such as triglyceride and/or plasma free fatty acid levels). The lipemia must clear between daily infusions. Precipitation occurring in parenteral nutrition admixtures as a result of incorrect admixture practices has been reported. Precipitate formation may occur as a result of incompatibility of calcium and phosphate salts. Liposyn III 30%, as a component of these admixtures, will obscure the presence of particulate matter (see DOSAGE AND ADMINISTRATION and MIXING INSTRUCTIONS FOR COMBINED ADMINISTRATION). Caution should be exercised in administering Liposyn III (intravenous fat emulsion) to patients with severe liver damage, pulmonary disease, anemia or blood coagulation disorders or when there is danger of fat embolism. The too rapid administration of Liposyn III can cause fluid and/or fat overloading resulting in dilution of serum electrolyte concentrations, over-hydration, congested states, pulmonary edema, impaired pulmonary diffusion capacity or metabolic acidosis. Caution should be exercised when admixing Liposyn III 30% (Intravenous Fat Emulsion). Studies have documented the stability of Liposyn III 30%, when admixed with Hospira electrolytes, Hospira trace metals, and Hospira Dextrose Injection, USP and Hospira Aminosyn II (amino acid) Injection. (Also see MIXING INSTRUCTIONS FOR COMBINED ADMINISTRATION under DOSAGE AND ADMINISTRATION). These compounded admixtures may be stored under refrigeration for up to 24 hours. Administration of admixtures should be completed within 24 hours after removal of refrigeration. Admixtures should be stored at room temperature (25°C) during this period. Reference should be made to the individual package inserts for detailed information on each component. The prime destabilizers of emulsions are excessive acidity (low pH) and inappropriate electrolyte content. Careful consideration should be given to the dosage levels of the divalent cations (Ca ++ and Mg ++ ) and phosphates administered, as these have been shown to cause emulsion instability. Amino acid solutions exert a buffering effect, protecting the emulsion. NOTE: The TPN admixture containers used in the stability studies were formulated to minimize lipid/container interactions. The principal bag materials were a nonphthalate polyvinylchloride (PVC) or the CR3 co-polyester material of which the Nutrimix ® dual-chamber flexible container is comprised. CR3 contains no plasticizers. 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.

ADVERSE REACTIONS 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. If symptoms and signs of acute respiratory distress develop, appropriate medical intervention should be instituted immediately and the cause of the distress investigated. The parenteral nutrition infusion should be replaced with a dextrose infusion (to prevent rebound hypoglycemia) and checked for the presence of particulate matter and oiling out of the emulsion (see MIXING INSTRUCTIONS FOR COMBINED ADMINISTRATION).