SOYBEAN OIL: 544 Adverse Event Reports & Safety Profile

DESCRIPTION Intralipid ® 20% (A 20% I.V.

Fat

Emulsion)

Pharmacy Bulk

Package is a sterile, non-pyrogenic fat emulsion intended as a source of calories and essential fatty acids for use in a pharmacy admixture program. It is made up of 20% 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. Intralipid ® 20% Pharmacy Bulk Package is not intended for direct infusion. It is a sterile dosage form which contains several single doses for use in the preparation of three-in-one or total nutrient admixtures (TNAs) in a pharmacy admixture program. The soybean oil is a refined natural product consisting of a mixture of neutral triglycerides of predominantly unsaturated fatty acids with the following structure: where 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: Linoleic acid C 18 H 32 O 2 Oleic acid C 18 H 34 O 2 Palmitic acid C 16 H 32 O 2 Linolenic acid C 18 H 30 O 2 Stearic acid C 18 H 36 O 2 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. R 3 is primarily either the choline or ethanolamine ester of phosphoric acid.

Phosphatidylcholine Phosphatidylethanolamine

Glycerin is chemically designated C 3 H 8 O 3 and is a clear colorless, hygroscopic syrupy liquid. It has the following structural formula: Intralipid ® 20% (A 20% I.V.

Fat

Emulsion) has an osmolality of approximately 350 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 2.0 kcal per mL of Intralipid ® 20%. 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. structure r1c r2c r3c structure structure structure structure structure structure structure figure stuct

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 )

AND ADMINISTRATION

• For intravenous infusion into a peripheral or central vein. ( 2.1 )
• Intralipid Pharmacy Bulk Package is only indicated for use in pharmacy admixture program for the preparation of three-in-one or total nutrition admixtures (TNAs). ( 2.2 )
• Protect the admixed PN solution from light. ( 2.2 , 16 )
• Recommended dosage depends on age, energy expenditure, clinical status, body weight, tolerance, ability to metabolize and eliminate lipids, and consideration of additional energy given to the patient. ( 2.3 )

Age Nutritional Requirements Initial Recommended

Dosage Maximum Dosage Birth to 2 years of age (including preterm and term neonates) 0.5 g/kg/day 3 g/kg/day Pediatric patients 2 to <12 years of age 1 to 2 g/kg/day 2.5 g/kg/day Pediatric patients 12 to 17 years of age 1 g/kg/day 2 g/kg/day Adults 1 g/kg/day (stable) ≤1 g/kg/day (critically ill) 2.5 g/kg/day

2.1 Important Administration Instructions

• Intralipid is prepared and administered by a healthcare provider in the inpatient setting. Patients and caregivers may prepare and administer Intralipid for home use after appropriate training by a trained healthcare provider.
• Intralipid is for intravenous infusion into a central or peripheral vein.
• Do not exceed the recommended maximum infusion rate in Table 1 [see Dosage and Administration ( 2.3 ) and Warnings and Precautions ( 5.1 )].
• Intralipid admixtures with osmolarity o Greater than or equal to 900 mOsm/L must be infused through a central vein. o Less than 900 mOsm/L may be administered either through a central or peripheral vein.
• Use a 1.2 micron in-line filter during administration.
• Use a dedicated infusion line without any connections. Do not connect multiple medications in series.
• To prevent air embolism, use a non-vented infusion set or close the vent on a vented set and fully evacuate residual gas in the bag prior to administration.
• Do not pressurize the flexible bag to increase flow rates, and if administration is controlled by a pumping device, turn off the pump before the bag runs dry.
• Do not use infusion sets and lines that contain di-2-ethylhexyl phthalate (DEHP), including infusion sets that contain polyvinyl chloride (PVC) components, because they contain DEHP as a plasticizer.
• Intralipid can be infused concurrently into the same vein as dextrose-amino acid solutions (as part of PN) by a Y-connector located near the infusion site; flow rates of each solution should be controlled separately by infusion pumps.
• After connecting the infusion set, start infusion of Intralipid immediately. Complete the infusion within 12 hours when using a Y-connector and within 24 hours when used as part of an admixture.

2.2 Preparation Instructions Use the following instructions to prepare single-dose 100 mL, 250 mL, and 500 mL Flexible containers for administration: 1.

Inspect

Bag

• Inspect the integrity indicator (Oxalert ® ) (A) before removing the overpouch.
• Discard the product if the indicator is black, overpouch is opened or damaged, emulsion color is not white, or seals of bag are broken. 2.

Remove

Overpouch

• Place the bag on a clean, flat surface.
• Tear the overpouch at notch and pull down.
• Discard the Oxalert sachet (A) and the oxygen absorber (B).
• Visually inspect the bag and contents for particulate matter and discoloration prior to administration. The lipid emulsion should be a homogenous liquid with a milky white appearance. If the mixture is not white or the emulsion has separated (noted by discoloration, phase separation, or oily droplets), or if particulates and/or leakage are observed, discard the bag. 3.

Spike

Bag

• Identify the infusion port ( blue cap with the arrow pointing away from the bag).
• Immediately before inserting the infusion set, break off the blue infusion port cap.
• Use infusion sets according to ISO Number 8536-4 with an external spike diameter of 5.5 to 5.7 mm and use a non-vented infusion set or close the air-inlet on a vented set.
• Use a 1.2 micron in-line filter for administration.
• Hold the base of the infusion port.
• Insert the spike through the infusion port by rotating your wrist slightly until the spike is inserted.
• Do not pierce the infusion port more than once. 4. Hang the bag
• On the hanger cut and start infusion.
• Discard unused portion.

Intralipid

100 mL, 250 mL, and 500 mL single-dose Flexible Containers

• After removing the overpouch, infuse immediately. If not used immediately, the product should be stored at 2°C to 8°C (36°F to 46°F) for no longer than 24 hours. After removal from storage, infuse within 12 hours when using a Y-connector and within 24 hours when used as part of an admixture.

Intralipid

1,000 mL Pharmacy Bulk Package

• For admixing use only and not for direct intravenous infusion . Prior to administration, transfer to a separate PN container for individual patient use.
• Transfer the contents through the blue infusion port using a suitable sterile transfer device or dispensing set. Discard any unused contents.
• Use the Pharmacy Bulk Package immediately for admixing after removal from the overpouch. If not used immediately, the product can be stored for no longer than 24 hours at 2°C to 8°C (36°F to 46°F). After removal from storage, and once the closure is penetrated, use Pharmacy Bulk Package contents within 4 hours.

Admixing

Instructions

• Prepare the admixture in PN containers using strict aseptic techniques to avoid microbial contamination.
• Do not add Intralipid to the PN container first; destabilization of the lipid may occur. The prime destabilizers of emulsions are excessive acidity (such as a pH <5) and inappropriate electrolyte content. Amino acid solutions exert buffering effects that protect the emulsion from destabilization. Give careful consideration to the addition of divalent cations (Ca++ and Mg++), which have been shown to cause emulsion instability.
• Do not inject additives directly into Intralipid.
• Intralipid may be mixed with amino acid and dextrose injections to produce “all-in-one” PN admixtures. The mixing sequence below must be followed for manual compounding to minimize pH-related problems by ensuring that typically acidic dextrose injections are not mixed with lipid emulsions alone; shake bags gently after each addition. o Transfer dextrose injection to the PN container. o Transfer amino acid injection. o Transfer Intralipid.
• Simultaneous transfer of amino acid injection, dextrose injection, and Intralipid to the PN container is also permitted; follow automated compounding device instructions as indicated. Use gentle agitation during admixing to minimize localized concentration effects.
• Additions to the PN admixtures should be evaluated by a pharmacist for compatibility. Questions about compatibility may be directed to Baxter Healthcare.
• Inspect the admixture to ensure that precipitates have not formed during preparation of the admixture and the emulsion has not separated. Discard the admixture if any of the above are observed.
• Infuse admixtures containing Intralipid immediately. If not used immediately, store admixtures under refrigeration at 2°C to 8°C (36°F to 46°F) for no longer than 24 hours. Infusion must be complete within 24 hours after removal from refrigeration. Discard any remaining admixture.
• Protect the admixed PN solution from light. intra-img-01.jpg intra-img-02.jpg intra-img-03.jpg intra-img-04.jpg intra-img-05.jpg

2.3 Recommended Dosage and Administration

• The recommended nutritional requirements of lipid and recommended dosages of Intralipid to be administered to meet those requirements for adults and pediatric patients are provided in Table 1 , along with recommendations for the initial and maximum infusion rates.
• The dosing of Intralipid depends on the patient's individual energy requirements influenced by age, body weight, tolerance, clinical status, and the ability to metabolize and eliminate lipids.
• When determining dose, energy supplied by dextrose and amino acids from PN, as well as energy from oral or enteral nutrition, has to be taken into account. Energy and lipid provided from lipid-based medications should also be taken into account (e.g., propofol).
• Prior to administration of Intralipid, correct severe fluid and electrolyte disorders and measure serum triglyceride levels to establish a baseline value. In patients with elevated triglyceride levels, initiate Intralipid at a lower dosage and titrate in smaller increments, monitoring the triglyceride levels with each adjustment [see Warnings and Precautions ( 5.7 )] .

Table

1: Recommended Pediatric and Adult Dosage and Infusion Rate * The neonatal period is defined as including term, post-term, and preterm neonates. The neonatal period for term and post-term neonates is the day of birth plus 27 days. For preterm neonates, the neonatal period is defined as the day of birth through the expected age of delivery plus 27 days (i.e., 44 weeks post-menstrual age). ** Daily dosage should also not exceed a maximum of 60% of total energy requirements [see Overdosage ( 10 )].

Age Nutritional Requirements Direct Infusion

Rate Recommended Initial Dosage and Maximum Dosage Initial Maximum Birth to 2 years of age (including preterm and term neonates*) [see Warnings and Precautions ( 5.1 )]

Initial

0.5 g/kg/day not to exceed 3 g/kg/day** 0.1 mL/kg/hour for the first 10 to 15 minutes; gradually increase to the required rate after 15 minutes 0.75 mL/kg/hour Pediatric patients 2 to <12 years of age Initial 1 to 2 g/kg/day not to exceed 2.5 g/kg/day*** 0.2 to 0.4 mL/kg/hour for the first 10 to 15 minutes; gradually increase to the required rate after 15 minutes 0.75 mL/kg/hour Pediatric patients 12 to 17 years of age Initial 1 g/kg/day not to exceed 2 g/kg/day** 0.2 mL/kg/hour for the first 10 to 15 minutes; gradually increase to the required rate after 15 minutes 0.75 mL/kg/hour Adults 1 g/kg/day in stable patients ≤1 g/kg/day in critically ill patients not to exceed 2.5 g/kg/day; not more than 500 mL of Intralipid should be infused on the first day of therapy** 0.2 mL/kg/hour for the first 10 to 15 minutes; gradually increase to the required rate after 30 minutes 0.5 mL/kg/hour Dosage Modifications in Patients with Essential Fatty Acid Deficiency When Intralipid is administered to correct essential fatty acid deficiency (EFAD), supply 8% to 10% of caloric input from Intralipid in order to provide adequate amounts of linoleic and linolenic acids.

CONTRAINDICATIONS Intralipid is contraindicated in patients with: Disturbances of normal fat metabolism such as pathologic hyperlipemia, lipoid nephrosis or acute pancreatitis if accompanied by hyperlipidemia. Known hypersensitivity to egg, soybean, peanut protein, or to any of the active ingredients or excipients in Intralipid 30%. INTRALIPID 30% PHARMACY BULK PACKAGE IS NOT INTENDED FOR DIRECT INTRAVENOUS ADMINISTRATION. DILUTING INTRALIPID 30% TO A 10% OR 20% CONCENTRATION WITH AN INTRAVENOUS FLUID SUCH AS NORMAL SALINE OR OTHER DILUENT DOES NOT PRODUCE A DILUTION THAT IS EQUIVALENT IN COMPOSITION TO INTRALIPID 10% OR 20% I.V. FAT EMULSIONS, AND SUCH A DILUTION SHOULD NOT BE GIVEN BY DIRECT INTRAVENOUS ADMINISTRATION (FOR EXAMPLE, THROUGH A Y‑CONNECTOR).

REACTIONS Adverse reactions described elsewhere in this Prescribing Information are:

• Clinical Decompensation with Rapid Infusion of Intravenous Lipid Emulsion in Neonates and Infants [see Warnings and Precautions ( 5.1 )]
• Parenteral Nutrition-Associated Liver Disease and Other Hepatobiliary Disorders [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 )] Most common adverse drug reactions (≥5%) from clinical trials in adults were nausea, vomiting, and pyrexia. Most common adverse drug reactions (≥5%) from clinical trials in pediatric patients were anemia, vomiting, increased gamma-glutamyltransferase, and cholestasis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 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 compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Intralipid

20% or equivalent soybean oil lipid emulsions functioned as the comparator in trials of the 4-oil mixed lipid emulsion [see Clinical Studies ( 14 )]. The adverse reactions from these studies are included to present the clinical experience with Intralipid because Intralipid 30% is to be diluted down to 20% or lower for PN admixture. The safety database for Intralipid or equivalent soybean oil lipid emulsion exposure in these studies include 393 patients (230 adults; 163 pediatric) in 9 clinical trials. Adult patients were exposed for 5 days to 4 weeks in 5 clinical trials. Intralipid or equivalent soybean oil lipid emulsion was used as a component of PN which also included dextrose, amino acids, vitamins, and trace elements. Two of the 5 studies in adults were performed with Intralipid as a component of PN delivered in a 3-chamber bag.

Table

2: Adverse Reactions in >1% of Adult Patients Treated with Intralipid/Soybean Oil Emulsion Adverse Reaction Number of Patients in Soybean Oil Lipid Emulsion Group (N=230) Number of Patients in 4-Oil Mixed Lipid Emulsion Comparator Group (N=229)

Nausea

26 (11%) 20 (9%)

Vomiting

12 (5%) 15 (7%)

Pyrexia

11 (5%) 9 (4%)

Hypertension

9 (4%) 6 (3%)

Headache

7 (3%) 3 (1%)

Hyperglycemia

5 (2%) 12 (5%) Abdominal pain 5 (2%) 8 (4%)

Flatulence

4 (2%) 10 (4%) Blood triglycerides increased 4 (2%) 6 (3%)

Sepsis

4 (2%) 5 (2%)

Diarrhea

4 (2%) 3 (1%)

Pneumonia

4 (2%) 3 (1%)

Pruritus

4 (2%) 3 (1%) Gamma-glutamyltransferase increased 4 (2%) 2 (1%) Less common adverse reactions occurring in ≤1% of adult patients who received Intralipid or equivalent soybean oil lipid emulsion were dyspepsia, urinary tract infection, anemia, infection, dyspnea, cholestasis, dysgeusia, increased blood alkaline phosphatase, tachycardia, liver function test abnormalities, dizziness, rash, and thrombophlebitis.

The

163 patients treated with Intralipid in four pediatric trials consisted of 147 patients <28 days of age, 9 patients 28 days to <2 years of age, and 7 patients 2 to 7 years of age; the duration of exposure was 7 to 84 days. Fifty-six percent of the pediatric patients were female, and 85% were Caucasian. Most pediatric patients were preterm neonates with feeding intolerance or other conditions requiring short-term (<29 days) PN.

Table

3: Adverse Reactions in >1% of Pediatric Patients Treated with Intralipid Adverse Reaction Number of Patients in Intralipid Group (N=163) Number of Patients in 4-Oil Mixed Lipid Emulsion Comparator Group (N=170)

Anemia

33 (20%) 30 (18%)

Vomiting

16 (10%) 16 (9%) Gamma-glutamyltransferase increased 12 (7%) 10 (6%)

Cholestasis

10 (6%) 7 (4%)

Pyrexia

7 (4%) 7 (4%) C-reactive protein increased 7 (4%) 6 (4%)

Hyperbilirubinemia

7 (4%) 5 (3%) Bilirubin conjugated increased 7 (4%) 3 (2%) Nosocomial infection 6 (4%) 10 (6%) Blood alkaline phosphatase increased 6 (4%) 1 (1%) Abdominal pain 5 (3%) 4 (2%) Hematocrit decreased 5 (3%) 2 (1%) Metabolic acidosis 5 (3%) 2 (1%)

Diarrhea

4 (3%) 3 (2%)

Tachycardia

4 (3%) 3 (2%)

Thrombocytopenia

4 (3%) 3 (2%) Alanine aminotransferase increased 3 (2%) 1 (1%) Aspartate aminotransferase increased 3 (2%) 0 (0%) Parenteral nutrition-associated liver disease 3 (2%) 0 (0%) Less common adverse reactions occurring in ≤1% of pediatric patients who received Intralipid were hyperglycemia, sepsis, increased blood triglycerides, infection, fluid overload, hypertension, hypertriglyceridemia, rash, and hyperlipidemia. In a randomized active-controlled, double-blind, parallel-group, multi-center study that included 152 neonates and 9 patients ranging in age from 29 to 153 days who were expected to require PN for at least 28 days, PNAC, a precursor to PNALD, developed more frequently in Intralipid-treated patients than in patients treated with a comparator 4-oil mixed lipid emulsion. PNAC (defined as direct bilirubin >2 mg/dL with a second confirmed elevation >2 mg/dL at least 7 days later) occurred in 11.5% (9/78) in Intralipid-treated patients and 2.4% (2/83) of patients treated with a 4-oil mixed lipid emulsion. Most PNAC events occurred in patients who were treated for longer than 28 days. The estimated cumulative incidence of PNAC is shown in the Kaplan-Meier cumulative incidence curve in Figure 1 [see Pediatric Clinical Studies ( 14.2 )] .

Figure

1: Cumulative Incidence Curve of Time to Parenteral Nutrition-Associated Cholestasis (PNAC) with Standard Error Bars intra-graph-01.jpg

6.2 Postmarketing Experience The following adverse reactions from voluntary reports have been reported with Intralipid. Because many of these reactions were 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. Cardiac disorders: palpitations Gastrointestinal disorders: vomiting, nausea General disorders and administration site conditions: chills, chest discomfort, pyrexia Nervous system disorders: dizziness Respiratory, thoracic, and mediastinal disorders : dyspnea Immune system disorders: hypersensitivity reactions, including anaphylaxis <span class="opacity-50 text-xs">[see Contraindications ( 4 ), Warnings and Precautions ( 5.3 )]</span> Vascular disorders : phlebitis Blood and lymphatic system disorders : hypercoagulability

AND PRECAUTIONS

• Risk of 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.

When Intralipid

30% is diluted to 20%, strictly adhere to the recommended total daily dosage; the hourly infusion rate should not exceed 0.125 g/kg/hour for neonates and infants. ( 5.1 , 8.4 )

• Risk of Parenteral Nutrition-Associated Liver Disease (PNALD): Increased risk in patients who receive PN for extended periods of time, especially preterm neonates. Monitor liver function tests; if abnormalities occur consider discontinuation or dosage reduction. ( 5.2 , 6.1 , 8.4 )
• Hypersensitivity Reactions: Monitor for signs or symptoms. Discontinue infusion if reactions occur. ( 5.3 )
• Risk of Infections, Fat Overload Syndrome, Refeeding Syndrome, and 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 Emulsions 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.

Intralipid

30% Pharmacy Bulk Package is not intended for direct infusion. When it is diluted to 20%, strictly adhere to the recommended total daily dosage; the hourly infusion rate should not exceed 0.125 g/kg/hour. 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 or 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 Intralipid, have been associated with development of PNALD. In a randomized study of neonates and infants expected to be treated with PN for at least 28 days, parenteral nutrition-associated cholestasis (PNAC), a precursor to PNALD, developed more frequently in Intralipid-treated patients than patients treated with a 4-oil mixed lipid emulsion. <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Use in Specific Populations ( 8.4 )]</span> . Monitor liver tests in patients treated with admixtures containing Intralipid 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 admixtures containing Intralipid. Patients developing signs of hepatobiliary disorders should be assessed early to determine whether these conditions are related to Intralipid use.

5.3 Hypersensitivity Reactions Intralipid 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 Intralipid administration <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . Intralipid is contraindicated in patients with known hypersensitivity to egg, soybean, peanut or any of the active or inactive ingredients in Intralipid <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . If a hypersensitivity reaction occurs, stop infusion of admixtures containing Intralipid immediately and initiate appropriate treatment and supportive measures.

5.4 Infections Parenteral nutrition, such as Intralipid, can support microbial growth and is an independent risk factor for the development of catheter-related bloodstream infections. To decrease the risk of infectious complications, ensure aseptic techniques are used for catheter placement, catheter maintenance, and preparation and administration of admixtures containing Intralipid. Monitor for signs and symptoms of infection including fever and chills, as well as laboratory test results that might indicate infection (including leukocytosis and hyperglycemia). Perform frequent checks of the intravenous catheter insertion site for edema, redness, and discharge.

5.5 Fat Overload Syndrome Fat overload syndrome is a rare condition that has been reported with intravenous lipid injectable emulsions and is characterized by a sudden deterioration in the patient&apos;s condition (e.g., fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, hepatomegaly, deteriorating liver function, and central nervous system manifestations such as coma). A reduced or limited ability to metabolize lipids, accompanied by prolonged plasma clearance (resulting in higher lipid levels), may result in this syndrome. Although fat overload syndrome has been most frequently observed when the recommended lipid dose or infusion rate was exceeded, cases have also been described when the lipid formulation was administered according to instructions. If signs or symptoms of fat overload syndrome occur, stop the infusion of admixtures containing Intralipid. The syndrome is usually reversible when the infusion of the lipid emulsion is stopped.

5.6 Refeeding Syndrome Administering PN to severely malnourished patients may result in refeeding syndrome, which is characterized by the intracellular shift of potassium, phosphorus, and magnesium as patients become anabolic. Thiamine deficiency and fluid retention may also develop. To prevent these complications, closely monitor severely malnourished patients and slowly increase their nutrient intake.

5.7 Hypertriglyceridemia The use of Intralipid is contraindicated in patients with hypertriglyceridemia with serum triglyceride concentrations &gt;1,000 mg/dL. Patients with conditions such as inherited lipid disorders, obesity, diabetes mellitus, or metabolic syndromes have a higher risk of developing hypertriglyceridemia with the use of Intralipid. In addition, patients with hypertriglyceridemia may have worsening of their hypertriglyceridemia with administration of Intralipid. Excessive dextrose administration may further increase such risk. Evaluate patients&apos; capacity to metabolize and eliminate the infused lipid emulsion by measuring serum triglycerides before the start of infusion (baseline value) and regularly throughout treatment. If triglyceride levels are above 400 mg/dL in adults, stop the Intralipid infusion and monitor serum triglyceride levels to avoid clinical consequences of hypertriglyceridemia such as pancreatitis. In pediatric patients with hypertriglyceridemia, lower triglyceride levels (i.e., below 400 mg/dL) may be associated with adverse reactions. Monitor serum triglyceride levels to avoid potential complications with hypertriglyceridemia such as pancreatitis, lipid pneumonitis, and neurologic changes, including kernicterus. To minimize the risk of new or worsening of hypertriglyceridemia, assess high-risk patients for their overall energy intake including other sources of lipids and dextrose, as well as concomitant drugs that may affect lipid and dextrose metabolism.

5.8 Aluminum Toxicity Intralipid contains no more than 25 mcg/L of aluminum. Prolonged PN administration in patients with renal impairment may result in aluminum reaching toxic levels. Preterm neonates are at greater risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions that contain aluminum. Patients with impaired kidney function, including preterm neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day can accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading in these patients may occur at even lower rates of administration.

5.9 Monitoring/Laboratory Tests Monitor fluid status closely in patients with pulmonary edema or heart failure. Throughout treatment, monitor serum triglycerides <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.7 )]</span>, essential fatty acids, fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count (including platelets), and coagulation parameters. The lipids contained in Intralipid may interfere with some laboratory tests (e.g., hemoglobin, lactate dehydrogenase, bilirubin, oxygen saturation) if blood is sampled before lipids have cleared from the bloodstream. Conduct these tests at least 6 hours after stopping the infusion. Intralipid contains vitamin K that may counteract anticoagulant activity <span class="opacity-50 text-xs">[see Drug Interactions ( 7 )]</span> .

PRECAUTIONS When Intralipid ® is administered, the patients capacity to eliminate the infused fat from the circulation must be monitored by use of an appropriate laboratory determination of serum triglycerides. Overdosage must be avoided. During long term intravenous nutrition with Intralipid ® , liver function tests should be performed. If these tests indicate that liver function is impaired, the therapy should be withdrawn. Frequent (some advise daily) platelet counts should be done in neonatal patients receiving parenteral nutrition with Intralipid ® . Drug product contains no more than 25 mcg/L of aluminum. Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies with Intralipid ® have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Pregnancy

Category C: Animal reproduction studies have not been conducted with Intralipid ® . It is also not known whether Intralipid ® can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Intralipid ® should be given to a pregnant woman only if clearly needed.

Nursing

Mothers: Caution should be exercised when Intralipid ® is administered to a nursing woman.

Pediatric

Use: See DOSAGE AND ADMINISTRATION. AVOID OVERDOSAGE ABSOLUTELY.

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.