1 INDICATIONS AND USAGE Intralipid ® is indicated as a source of calories and essential fatty acids for adult and pediatric patients requiring parenteral nutrition and as a source of essential fatty acids for prevention of essential fatty acid deficiency (EFAD).

Intralipid is indicated as a source of calories and essential fatty acids for adult and pediatric patients requiring parenteral nutrition (PN) and as a source of essential fatty acids for prevention of essential fatty acid deficiency (EFAD).

6 ADVERSE 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 [see Contraindications ( 4 ), Warnings and Precautions ( 5.3 )] Vascular disorders : phlebitis Blood and lymphatic system disorders : hypercoagulability