Soybean oil

12.1 Mechanism of Action Nutrilipid 20% administered intravenously provides biologically utilizable source of calories and essential fatty acids. Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation. Fatty acids are important for membrane structure and function, precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression. Nutrilipid 20% causes an increase in heat production, decrease in respiratory quotient, and increase in oxygen consumption following its administration.

1 INDICATIONS AND USAGE Nutrilipid ® 20% is indicated as a source of calories and essential fatty acids for parenteral nutrition and as a source of essential fatty acids when a deficiency occurs when oral or enteral nutrition is not possible, insufficient, or contraindicated. Nutrilipid 20% is indicated as a source of calories and essential fatty acids for parenteral nutrition and as a source of essential fatty acids when a deficiency occurs when oral or enteral nutrition is not possible, insufficient, or contraindicated. ( 1 )

2 DOSAGE AND ADMINISTRATION Nutrilipid 20% Pharmacy Bulk Package is not intended for direct intravenous administration. ( 2.1 ) For intravenous infusion through a peripheral or central line ( 2.1 ) Recommended dosage depends on age, energy expenditure, clinical status, body weight, tolerance, ability to metabolize and consideration of additional energy given to the patient. ( 2.4 ) For information on the age-appropriate infusion rate, see the full prescribing information. ( 2.4 , 5.1 ) Age Nutritional Requirements Initial Recommended Dosage Maximum Dosage Preterm and term infants (<1 year) 1 to 2 g/kg/day 3 g/kg/day Pediatric patients 1 to 10 years Pediatric patients 11 to <17 years 1 g/kg/day 2.5 g/kg/day Adults 1 to 1.5 g/kg/day 2.5 g/kg/day 2.1 Administration Instructions Nutrilipid 20% Pharmacy Bulk Package is not intended for direct intravenous administration. Nutrilipid 20% is for intravenous infusion through a peripheral or central line. When administered with dextrose and amino acids, the choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Do not exceed the recommended maximum infusion rate in Table 1 [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ]. Use a non-vented infusion set or close the air vent on a vented set. Use of a vented intravenous administration set with the vent in the open position could result in air embolism. Use a dedicated line without any connections. Multiple connections could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed. Use a 1.2 micron in-line filter. Nutrilipid 20% can be infused concurrently into the same vein as carbohydrate-amino acid solutions by means of a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps. Do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Conventional administration sets contain polyvinyl chloride (PVC) components that have DEHP as a plasticizer. 2.2 Preparation Instructions for Nutrilipid 20% Bags for Direct Infusion Caution: Nutrilipid 20% Pharmacy Bulk Package is not intended for direct intravenous administration. Step 1: Inspect infusion bag overwrap and primary bag and do not use if damaged. Inspect oxygen indicator and do not use if oxygen indicator is pink or dark pink. Use only if container and seals are intact. Step 2: To open, tear overwrap starting from the tear notches (Figure 1). Remove Nutrilipid 20% bag from overwrap and discard oxygen indicator, oxygen absorber and overwrap. Step 3: Inspect Nutrilipid 20% bag visually (Figure 2). Nutrilipid 20% is a homogenous white and milky, sterile, nonpyrogenic lipid injectable emulsion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Inspect Nutrilipid 20% to ensure that the emulsion has not separated. Discard the bag if any particulates or discoloration are observed. Step 4: Remove aluminum foil of outlet port at the bottom of the bag (Figure 3a) and attach administration set (Figure 3b). Do not use/penetrate blocked port. Step 5: Hang bag on IV Pole (Figure 4). If infusion pumps are used, flow rates of each parenteral fluid should be controlled with a separate pump. Do not connect flexible bags in series to avoid air embolism due to possible residual gas contained in the primary bag. Air embolism can result if residual gas in the bag is not fully evacuated prior to administration if the flexible bag is pressurized to increase flow rates. If administration is controlled by a pumping device, discontinue pumping action before the bag runs dry to avoid air embolism. Overwrap Illustration Figure 1 Tear Overwrap Figure 2 Inspect Bag Blocked port illustration Figure 3a and 3b Peel Foil and Insert Spike Do not use blocked port illustration Figure 4 Hang Bag 2.3 Preparation Instructions for Admixing Using Total Parenteral Nutrition Pooling Bags Prepare the admixture into pooling bags using strict aseptic techniques to avoid microbial contamination. Do not add additives directly to Nutrilipid 20% Pharmacy Bulk Package. Some additives may be incompatible and should not be used. If it is deemed advisable to introduce additives, prepare the admixture using strict aseptic techniques to avoid microbial contamination. Additions to the pooling bag should be evaluated by a pharmacist for compatibility. Questions about compatibility may be directed to B. Braun Medical Inc., Medical Affairs. Do not add Nutrilipid 20% to the pooling bag first; destabilization of the lipid may occur from such an admixture. 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: Manual Admixing Manually tran

6 ADVERSE REACTIONS Adverse Reactions described elsewhere in labeling: Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants [see Warnings and Precautions (5.1) ] Risk of Parenteral Nutrition Associated Liver Disease [see Warnings and Precautions (5.2) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Infections [see Warnings and Precautions (5.4) ] Fat Overload Syndrome [see Warnings and Precautions (5.5) ] Refeeding Syndrome [see Warnings and Precautions (5.6)] Hypertriglyceridemia [see Warnings and Precautions (5.7) ] Aluminum Toxicity [see Warnings and Precautions (5.8) ] Adverse reactions include administration site reactions (e.g., erythema, extravasation, pain, phlebitis, pruritus, swelling), hyperlipidemia, hypercoagulability, thrombophlebitis, thrombocytopenia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact B. Braun Medical Inc. at 1-833-425-1464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions reported with other intravenous lipid emulsions include hyperlipidemia, hypercoagulability, thrombophlebitis, and thrombocytopenia. Adverse reactions reported in long-term use with other intravenous lipid emulsions include hepatomegaly, jaundice due to central lobular cholestasis, splenomegaly, thrombocytopenia, leukopenia, abnormalities in liver function tests, brown pigmentation of the liver and overloading syndrome (focal seizures, fever, leukocytosis, hepatomegaly, splenomegaly and shock). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Nutrilipid 20%. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions: extravasation, infusion site erythema, infusion site pain, infusion site phlebitis, infusion site pruritus, and infusion site swelling. Immune system disorders: hypersensitivity reactions, including anaphylaxis [see Contraindications (4) , Warnings and Precautions (5.3) ].

7 DRUG INTERACTIONS Coumarin and coumarin derivatives, including warfarin: Anticoagulant activity may be counteracted; monitor laboratory parameters (7.1) 7.1 Coumarin and Coumarin Derivatives The soybean oil in Nutrilipid 20% contains vitamin K1. Vitamin K can reverse the anticoagulant activity of coumarin and coumarin derivatives, including warfarin, which work by blocking recycling of vitamin K. Monitor laboratory parameters for anticoagulant activity in patients who are on both Nutrilipid 20% and coumarin or coumarin derivatives.