Soybean Oil

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 )

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.

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 block

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) ].

5 WARNINGS AND PRECAUTIONS Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants : Acute respiratory distress, metabolic acidosis, and death after rapid infusion of intravenous lipid emulsions have been reported. ( 5.1, 8.4 ) Parenteral Nutrition-Associated Liver Disease : Increased risk in patients who receive parenteral nutrition for greater than 2 weeks, especially preterm neonates. Monitor liver tests; if abnormalities occur, consider discontinuation or dosage reduction. ( 5.2, 8.4 ) Hypersensitivity reactions: Monitor for signs or symptoms. Discontinue infusion if reactions occur. ( 5.3 ) Infections, Fat Overload Syndrome, and Refeeding Syndrome, Hypertriglyceridemia: Monitor for signs and symptoms; monitor laboratory parameters. ( 5.4 , 5.5 , 5.6, 5.7 ) Aluminum Toxicity : Increased risk in patients with renal impairment, including preterm neonates. ( 5.8, 8.4 ) 5.1 Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants In the postmarketing setting, serious adverse reactions including acute respiratory distress, metabolic acidosis, and death have been reported in neonates and infants after rapid infusion of intravenous lipid emulsions. Hypertriglyceridemia was commonly reported. Strictly adhere to the recommended total daily dosage; the hourly infusion rate should not exceed 0.75 mL/kg/hour [see Dosage and Administration (2.4) ]. Preterm and small for gestational age infants have poor clearance of intravenous lipid emulsion and increased free fatty acid plasma levels following lipid emulsion infusion. Carefully monitor the infant’s ability to eliminate the infused lipids from the circulation (e.g., measure serum triglycerides and/or plasma free fatty acid levels). If signs of poor clearance of lipids from the circulation occur, stop the infusion and initiate a medical evaluation [see Warnings and Precautions (5.5, 5.7) and Overdosage (10) ]. 5.2 Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders Risk of Parenteral Nutrition-Associated Liver Disease Parenteral nutrition-associated liver disease (PNALD), also referred to as intestinal failure-associated liver disease (IFALD), can present as cholestasis or hepatic steatosis, and may progress to steatohepatitis with fibrosis and cirrhosis (possibly leading to chronic hepatic failure). The etiology of PNALD is multifactorial; however, intravenously administered phytosterols (plant sterols) contained in plant-derived lipid emulsions, including Nutrilipid 20%, have been associated with development of PNALD. Monitor liver tests in patients treated with Nutrilipid 20% and consider discontinuation or dosage reduction if abnormalities occur. Other Hepatobiliary Disorders Hepatobiliary disorders including cholecystitis and cholelithiasis have developed in some PN-treated patients without preexisting liver disease. Monitor liver tests when administering Nutrilipid 20%. Patients developing signs of hepatobiliary disorders should be assessed early to determine whether these conditions are related to Nutrilipid 20% use. 5.3 Hypersensitivity Reactions Nutrilipid 20% contains soybean oil and egg phospholipids which may cause hypersensitivity reactions. Cross reactions have been observed between soybean and peanut. In postmarketing experience, anaphylaxis has been reported following Nutrilipid administration [see Adverse Reactions (6.2) ]. Nutrilipid 20% is contraindicated in patients with known hypersensitivity to egg, soybean, peanut, or any of the active or inactive ingredients in Nutrilipid 20% [see Contraindications (4)] . If a hypersensitivity reaction occurs, stop infusion of Nutrilipid 20% immediately and initiate appropriate treatment and supportive measures. 5.4 Infections Lipid emulsions, such as Nutrilipid 20%, can support microbial growth and are an independent risk factor for the development of catheter-related bloodstream infections. To decrease the risk of inf

4 CONTRAINDICATIONS Nutrilipid 20% injection is contraindicated in patients who have: Known hypersensitivity to egg, soybean, peanut, or any of the active or inactive ingredients in Nutrilipid 20% [see Warnings and Precautions (5.3) ]. Severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglyceride >1,000 mg/dL) [see Warnings and Precautions (5.7) ]. Known hypersensitivity to egg, soybean, peanut, or any of the active or inactive ingredients. ( 4 ) Severe disorders of lipid metabolism characterized by hypertriglyceridemia (serum triglycerides >1,000 mg/dL). ( 4, 5.7 )

10 OVERDOSAGE In the event of overdose, serious adverse reactions may result [see Warnings and Precautions (5.1, 5.5) ]. Stop the infusion to allow lipids to clear from serum. The effects are usually reversible after the lipid infusion is stopped. If medically appropriate, further intervention may be indicated. The lipid administered and fatty acids produced are not dialyzable.