Leucine, Phenylalanine, Lysine, Methionine, Isoleucine, Valine, Histidine, Threonine, Tryptophan, Alanine, Glycine, Arginine, Proline, Serine, Tyrosine, Dibasic Potassium Phosphate, Magnesium Chloride, Sodium Chloride, Calcium Chloride, Dextrose

1 INDICATIONS AND USAGE CLINIMIX E is indicated as a source of calories, protein, and electrolytes for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. CLINIMIX E may be used to treat negative nitrogen balance in patients. CLINIMIX E is indicated as a source of calories, protein, and electrolytes for patients requiring parenteral nutrition when oral or enteral nutrition is not possible, insufficient, or contraindicated. CLINIMIX E may be used to treat negative nitrogen balance in patients. ( 1 )

2 DOSAGE AND ADMINISTRATION See full prescribing information for information on preparation, administration, instructions for use, dosing considerations, including the recommended dosage in adults and pediatrics, and dosage modifications in patients with kidney disease. ( 2.1 , 2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 ) 2.1 Preparation Prior to Administration • CLINIMIX E is available in a three port container configuration and a two port container configuration. • Three Port Container: the ports consist of one medication port, one additive port and one outlet port. Additives can be introduced to the container through the medication port and lipids through the additive port on the three port container. • Two Port Container: the ports consist of one medication port and one outlet port. Additives, including lipids, can be introduced to the container through the medication port on the two port container. • Tear protective overwrap at slit and remove solution container. Small amounts of moisture may be found on the solution container from water permeating from inside the container. The amount of permeated water is insufficient to affect the solution significantly. If larger amounts of water are found, the container should be checked for tears or leaks. • Inspect the container prior to activation. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Evaluate the following: • If the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired. • Check to ensure seal between chambers is intact, solutions are contained in separate chambers, and the content of the individual chambers is clear, colorless or slightly yellow. Discard if the seal is broken or if the solution is bright yellow or yellowish brown. • Check for minute leaks by separately squeezing each chamber. If external leaks or leakage between the chambers are found, discard solution as sterility or stability may be impaired. • Lipids and/or additives can be introduced to the container after opening seal between chambers. Because additives may be incompatible, evaluate all additions to the plastic container for compatibility. Activate chambers of container prior to introduction of additives. Mix thoroughly when additives have been introduced. Supplemental medication may be added with a 19 to 22 gauge needle through the medication port. • Calcium and phosphate ratios must be considered. Excess addition of calcium and phosphate, especially in the form of mineral salts, may result in the formation of calcium phosphate precipitates [see Warnings and Precautions (5.1) ]. • Inspect the container to ensure precipitates have not formed during the mixing or addition of additives. A slight yellow color does not alter the quality and efficacy of this product. If lipid has been added, ensure the emulsion has not separated. Separation of the emulsion can be visibly identified by a yellowish streaking or the accumulation of yellowish droplets in the mixed emulsion. Discard the admixture if any of the above are observed. 2.2 Important Administration Instructions • Set the vent to the closed position on a vented intravenous administration set to prevent air embolism. • Use a dedicated line without any connections to avoid air embolism. • CLINIMIX E is for intravenous infusion only into a central or peripheral vein. The choice of a central or peripheral venous route should depend on the osmolarity of the final infusate. Solutions with osmolarity of 900 mOsm/L or greater must be infused through a central catheter [see Warnings and Precautions (5.7) ]. • For central vein infusion only: CLINIMIX E 4.25/10, 5/15, 5/20, 8/10, 8/14 • For central or peripheral vein infusion: CLINIMIX E 2.75/5 and 4.25/5 • The solution should be inspected for precipitates before admixing, after admixing, and again before administration. • Use a 0.22 micron filter for administration of CLINIMIX E. If a lipid is also administered, use a 1.2 micron filter. • If lipid emulsion is added, do not use administration sets and lines that contain di-2-ethylhexyl phthalate (DEHP). Administration sets that contain polyvinyl chloride (PVC) components have DEHP as a plasticizer. • Ceftriaxone must not be administered simultaneously with calcium-containing intravenous solutions such as CLINIMIX E via a Y-site. However, in patients other than neonates, ceftriaxone and CLINIMIX E may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid [see Contraindications (4) , Warnings and Precautions (5.2) ] . 2.3 Instructions for Use 1. Open by tearing protective overwrap at slit and remove solution container. The two port container includes an oxygen-absorbing sachet. Discard the oxygen-absorbing sachet after removal from the overwrap. 2. To proceed with activation, the container should be at room temperature. Lay the room temperature container onto a flat surface. Grasp the container firmly on each side of the top of the container ( Figure 1 ). 3. Starting from the top, using some pressure, slowly roll the container to open seal between chambers as shown in Figure 2 . Do not pull or rip the seal apart. The seal must be completely opened towards the port side of the container. The upper section of the seal towards the hanger side can remain unbroken. 4. Mix the contents thoroughly by inverting the container upside down to ensure a homogenous admixture ( Figure 3 ). 5. Once the container is mixed, check for leaks. 6. Make additions (if prescribed). Because additives may be incompatible, evaluate all additions to the container for compatibility and stability of the resulting preparation. Consult with pharmacist, if available. Questions about compatibility may be directed to Baxter. If it is deemed advisable to introduce additives, use aseptic technique. For information on adding lipid emulsions see Dosage and Administration (2.4) . a. Prepare medication port. b. Using syringe with 19 to 22 gauge needle, puncture resealable medication port and inject. c. Mix solution and medication thoroughly ( Figure 3 ). For high density medication (high specific gravity), such as potassium chloride, squeeze ports while ports are upright and mix thoroughly. 7. Inspect final solution for discoloration and particulate matter. Check for leaks. 8. Spike and hang container. a. Suspend container from eyelet support. b. Twist off protector from outlet port at bottom of container ( Figure 4 ). c. Attach administration set. Refer to complete directions accompanying set. For single dose only. Discard unused portion. Figures 1 – 4 (Three Port Container): Figures 1 – 4 (Two Port Container): Instructions on Storage Storage After Removal of Overwrap: Once removed from the protective overwrap, mixed (peel seal activated) or unmixed (peel seal intact), CLINIMIX E solutions may be stored under refrigeration for up to 9 days. Storage Once any Additive is Added: Use promptly after mixing. Any storage with additives should be under refrigeration and limited to a brief period of time, less than 24 hours. After removal from refrigeration, use promptly and complete the infusion within 24 hours. Any remaining mixture must be discarded. Protect the activated parenteral nutrition solution from light. Figure 1-4 Clinimix E Figures 1-4 - (Two Port Container) 2.4 Preparation and Addition of Lipid Emulsion Three Port Container 1. Prior to adding lipid emulsion, mix amino acid and dextrose injection as shown in Figures 1-3 . 2. Prepare lipid emulsion transfer set following instructions provided. 3. Attach transfer set to lipid emulsion container using aseptic technique. 4. Twist off protector on the additive port of the container. 5. Attach the transfer set to the exposed additive port. 6. Open clamp on transfer set. 7. After completing transfer, use appropriate plastic clamp or metal ferrule to seal off additive port tube. 8. Remove transfer set. 9. Mix contents of container thoroughly. Inspect final solution for discoloration and particulate matter. Check for leaks. Two Port Container 1. Prior to adding lipid emulsion, mix amino acid and dextrose injection as shown in Figures 1-3. 2. Prepare lipid emulsion transfer set following instructions provided. 3. Attach transfer set to lipid emulsion container using aseptic technique. 4. Prepare medication port. 5. Using a 19 to 22 gauge needle, puncture resealable medication port. 6. Open clamp on transfer set and transfer lipid emulsion. 7. Remove needle. 8. Mix contents of container thoroughly. Inspect final solution for discoloration and particulate matter. Check for leaks. Storage Once Lipids are Added: Use promptly after mixing. Any storage with additives should be under refrigeration and limited to a brief period of time, no longer than 24 hours. After removal from refrigeration, use promptly and complete the infusion within 24 hours. Any mixture remaining must be discarded. 2.5 Dosing Considerations • The dosage of CLINIMIX E should be individualized based on the patient’s clinical condition (ability to adequately metabolize amino acids and dextrose), body weight and nutritional/fluid requirements, as well as additional energy given orally/enterally to the patient. Prior to initiating CLINIMIX E the following patient information should be reviewed: all concomitant medications, gastrointestinal function and laboratory data such as electrolytes (including magnesium, calcium, and phosphorus), glucose, urea/creatinine, liver panel, complete blood count and triglyceride level (if adding lipid emulsion). Refer to the complete prescribing information of lipid emulsion for dosing information. • CLINIMIX E formulations have varying concentrations of protein, carbohydrate and a standard concentration of electrolytes; thus infusion rates to achieve requirements will vary. Protein, caloric, fluid and electrolyte requirements all need to be taken into consideration when determining individual patient dosage needs. • The dosage selection is based only on the recommended protein requirements. The maximum dextrose infusion rates and calorie and fluid requirements must also be considered when determining the clinically appropriate infusion rate for patients. • CLINIMIX E meets the total nutritional requirements for protein and dextrose in stable patients, and can be individualized to meet specific needs with the addition of nutrients. • Total daily fluid requirements can be met beyond the volume of amino acids solution by supplementing with non-carbohydrate or carbohydrate-containing electrolyte solutions. In many patients, provision of adequate calories in the form of hypertonic dextrose may require the administration of exogenous insulin to prevent hyperglycemia and glycosuria. • Prior to administration of CLINIMIX E correct severe fluid, electrolyte and acid-base disorders. • Monitor levels of serum potassium during therapy. It may be necessary to add additional potassium to the CLINIMIX E admixture. • Lipid emulsion administration should be considered with prolonged use (more than 5 days) of CLINIMIX E in order to prevent essential fatty acid deficiency (EFAD). Serum lipids should be monitored for evidence of EFAD in patients maintained on fat-free parenteral nutrition. See prescribing information of lipid emulsion. • The flow rate should be increased gradually. The flow rate must be adjusted taking into account the dose being administered, the daily volume intake, and the duration of the infusion. 2.6 Recommended Dosage in Adults The recommended daily nutritional requirements for protein and dextrose compared to the amount of nutrition provided by CLINIMIX E are shown in Table 1 . As indicated on an individual basis, maintenance vitamins, additional electrolytes, trace elements and other components (including lipids) should be administered as required to prevent deficiencies and complications from developing. The maximum infusion rates in adult patients are show in Table 2 . In addition to meeting protein needs, the administration rate should be governed, especially during the first few day of therapy, by the patient’s tolerance to dextrose. Daily intake of amino acids and dextrose should be increased gradually to the maximum required dose as indicated by frequent determinations of blood glucose levels. Table 1: Nutritional Comparison – Adult Patients Recommended CLINIMIX E Adult Dosage CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Fluid (mL/kg/day) 29 to 40 19 to 40 19 to 40 16 to 40 16 to 40 10 to 25 10 to 25 Protein Protein is provided as amino acids. When infused intravenously amino acids are metabolized and utilized as the building blocks of protein. (g/kg/day) (Nitrogen g/kg/day) 0.8 to 1.1 (0.13 to 0.18) 0.8 to 1.7 (0.13 to 0.27) 0.8 to 1.7 (0.13 to 0.27) 0.8 to 2 (0.13 to 0.32) 0.8 to 2 (0.13 to 0.32) 0.8 to 2 (0.13 to 0.32) 0.8 to 2 (0.13 to 0.32) Dextrose (g/kg/day) 1.45 to 2 0.95 to 2 1.9 to 4 2.4 to 6 3.2 to 8 1 to 2.5 1.4 to 3.5 Table 2: Maximum Infusion Rate in Adult Patients Maximum Infusion Rates in Adults Patients CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Maximum Infusion Rate (mL/kg/hour) 3.6 2.4 2.4 1.67 1.25 1.3 1.3 Corresponding infusion rate Amino Acid (g/kg/hour) 0.1 Rate limiting factor 0.1 0.1 0.08 0.06 0.1 0.1 Dextrose (g/kg/hour) 0.18 0.12 0.24 0.25 0.25 0.13 0.18 2.7 Dosage Modifications in Patients with Kidney Disease Prior to administration, correct severe fluid or electrolyte imbalances. Closely monitor serum electrolyte levels and adjust the volume of CLINIMIX E administered as required [see Warnings and Precautions (5.11) ] . Chronic kidney disease patients with less than nephrotic range proteinuria require 0.8 g of protein/kg/day. Chronic kidney disease patients with nephrotic range proteinuria require 0.8 g of protein/kg/day plus 1 g of protein for each gram of proteinuria. Patients needing dialysis should receive from 1.2 g of protein/kg/day up to a maximum of 2.5 g of protein/kg/day depending on the nutritional status and the dialysis modality. Serum electrolyte levels should be closely monitored. The CLINIMIX E dosage can be adjusted based on the severity of kidney disease, supplementing protein as indicated. If required, additional amino acids may be added to the CLINIMIX E container or infused separately. Compatibility of additions should be evaluated by a pharmacist and questions may be directed to Baxter. 2.8 Recommended Dosage in Pediatric Patients The dosage and constant infusion rate of intravenous dextrose must be selected with caution in pediatric patients, particularly neonates and low weight infants, because of the increased risk of hyperglycemia/hypoglycemia [see Use in Specific Populations (8.4) ] . Frequent monitoring of serum glucose concentrations is required when dextrose is prescribed to pediatric patients, particularly neonates and low birth weight infants. The infusion rate and volume should be determined by the consulting physician experienced in pediatric intravenous fluid therapy. In pediatric patients, CLINIMIX E is dosed on the basis of protein provided as amino acids. The recommended dosage, by age group is provided in Tables 3 - 6 . Infusion rates are based on protein and do not take carbohydrates, fluid or electrolytes into consideration. This product does not contain the amino acids cysteine and taurine, considered conditionally essential for neonates and infants. If possible, these amino acids should be added to this product if used in this pediatric population. Table 3: Preterm and Term Infants Less than 1 Month of Age Recommended CLINIMIX E Dosage in Preterm and Term Infants Less than 1 Month of Age CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Infusion Rate Range (mL/kg/hr) 4.5 to 6 2.9 to 3.9 2.9 to 3.9 2.5 to 3.3 2.5 to 3.3 1.6 to 2.1 1.6 to 2.1 Fluid (mL/kg/day) 108 to 144 70 to 94 70 to 94 60 to 79 60 to 79 38.4 to 50 38.4 to 50 Protein Protein is provided as amino acids. When infused intravenously amino acids are metabolized and utilized as the building blocks of protein. (g/kg/day) (Nitrogen g/kg/day) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) 3 to 4 (0.48 to 0.64) Dextrose (g/kg/day) 5.4 to 7.2 3.5 to 4.7 7 to 9.4 9 to 11.9 12 to 15.8 3.8 to 5 5.4 to 7 Table 4: Pediatric Patients 1 Month to Less than 1 Year of Age Recommended CLINIMIX E Dosage in Pediatric Patients 1 Month to Less than 1 Year of Age CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Infusion Rate Range (mL/kg/hr) 3 to 4.5 2 to 2.9 2 to 2.9 1.7 to 2.5 1.7 to 2.5 1 to 1.6 1 to 1.6 Fluid (mL/kg/day) 72 to 108 48 to 70 48 to 70 41 to 60 41 to 60 24 to 38.4 24 to 38.4 Protein Protein is provided as amino acids. When infused intravenously amino acids are metabolized and utilized as the building blocks of protein. (g/kg/day) (Nitrogen g/kg/day) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) 2 to 3 (0.32 to 0.48) Dextrose (g/kg/day) 3.6 to 5.4 2.4 to 3.5 4.8 to 7 6.1 to 9 8.2 to 12 2.4 to 3.8 3.4 to 5.4 Table 5: Pediatric Patients 1 Year to Less than 11 Years of Age Recommended CLINIMIX E Dosage in Pediatric Patients 1 Year to Less than 11 Years of Age CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Infusion Rate Range (mL/kg/hr) 1.5 to 3 1 to 2 1 to 2 0.8 to 1.7 0.8 to 1.7 0.5 to 1 0.5 to 1 Fluid (mL/kg/day) 36 to 72 24 to 48 24 to 48 19 to 41 19 to 41 12 to 24 12 to 24 Protein Protein is provided as amino acids. When infused intravenously amino acids are metabolized and utilized as the building blocks of protein. (g/kg/day) (Nitrogen g/kg/day) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) 1 to 2 (0.16 to 0.32) Dextrose (g/kg/day) 1.8 to 3.6 1.2 to 2.4 2.4 to 4.8 2.9 to 6.1 3.8 to 8.2 1.2 to 2.4 1.7 to 3.4 Table 6: Pediatric Patients 11 Years to 17 Years of Age Recommended CLINIMIX E Dosage in Pediatric Patients 11 Years to 17 Years of Age CLINIMIX E 2.75/5 CLINIMIX E 4.25/5 CLINIMIX E 4.25/10 CLINIMIX E 5/15 CLINIMIX E 5/20 CLINIMIX E 8/10 CLINIMIX E 8/14 Infusion Rate Range (mL/kg/hr) 1.2 to 2.3 0.8 to 1.5 0.8 to 1.5 0.7 to 1.3 0.7 to 1.3 0.4 to 0.8 0.4 to 0.8 Fluid (mL/kg/day) 29 to 55 19 to 36 19 to 36 17 to 31 17 to 31 9.6 to 19.2 9.6 to 19.2 Protein Protein is provided as amino acids. When infused intravenously amino acids are metabolized and utilized as the building blocks of protein. (g/kg/day) (Nitrogen g/kg/day) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) 0.8 to 1.5 (0.13 to 0.24) Dextrose (g/kg/day) 1.4 to 2.8 1 to 1.8 1.9 to 3.6 2.5 to 4.7 3.4 to 6.2 1 to 1.9 1.4 to 2.7 2.9 Discontinuation of CLINIMIX E injection To reduce the risk of hypoglycemia after discontinuation, a gradual decrease in flow rate in the last hour of infusion should be considered.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information. • Pulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1) ] • Death in neonates due to calcium-ceftriaxone precipitates [see Warnings and Precautions (5.2) ] • Hypersensitivity reactions [see Warnings and Precautions (5.3) ] • Risk of Infections [see Warnings and Precautions (5.4) ] • Refeeding syndrome [see Warnings and Precautions (5.5) ] • Hyperglycemia or hyperosmolar hyperglycemic state [see Warnings and Precautions (5.6) ] • Vein damage and thrombosis [see Warnings and Precautions (5.7) ] • Hepatobiliary disorders [see Warnings and Precautions (5.8) ] • Parenteral Nutrition Associated Liver Disease (PNALD) [see Warnings and Precautions (5.10) ] • Electrolyte imbalance and fluid overload [see Warnings and Precautions (5.11) ] The following adverse reactions from voluntary reports or clinical studies have been reported with CLINIMIX E. 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. • Diuresis • Extravasation • Glycosuria • Hyperglycemia • Hyperosmolar coma Adverse reactions include diuresis, extravasation, glycosuria, hyperglycemia, and hyperosmolar coma. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch