INDICATIONS & USAGE SECTION.


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

CONTRAINDICATIONS SECTION.


4 CONTRAINDICATIONS. The use of CLINIMIX is contraindicated in:oPatients with known hypersensitivity to one or more amino acids or dextrose [see Warnings and Precautions (5.2)]. oPatients with inborn errors of amino acid metabolism due to risk of severe metabolic and neurologic complications. oPatients with pulmonary edema or acidosis due to low cardiac output.. oPatients with known hypersensitivity to one or more amino acids or dextrose [see Warnings and Precautions (5.2)]. oPatients with inborn errors of amino acid metabolism due to risk of severe metabolic and neurologic complications. oPatients with pulmonary edema or acidosis due to low cardiac output.. oKnown hypersensitivity to one or more amino acids or dextrose. (4)oInborn errors of amino acid metabolism. (4)oPatients with pulmonary edema or acidosis due to low cardiac output. (4). oKnown hypersensitivity to one or more amino acids or dextrose. (4). oInborn errors of amino acid metabolism. (4). oPatients with pulmonary edema or acidosis due to low cardiac output. (4).

ADVERSE REACTIONS SECTION.


6 ADVERSE REACTIONS. The following serious adverse reactions are discussed in greater detail in other sections of the prescribing information.oPulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]oHypersensitivity reactions [see Warnings and Precautions (5.2)]oRisk of Infections [see Warnings and Precautions (5.3)]oRefeeding syndrome [see Warnings and Precautions (5.4)]oHyperglycemia or hyperosmolar hyperglycemic state [see Warnings and Precautions (5.5)]oVein damage and thrombosis [see Warnings and Precautions (5.6)]oHepatobiliary disorders [see Warnings and Precautions (5.7)]oParenteral Nutrition Associated Liver Disease [see Warnings and Precautions (5.9) ]oElectrolyte imbalance and fluid overload [see Warnings and Precautions (5.10)]The following adverse reactions from voluntary reports or clinical studies have been reported with CLINIMIX. Because many of these reactions were reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.oDiuresisoExtravasationoGlycosuriaoHyperglycemiaoHyperosmolar coma. oPulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]. oHypersensitivity reactions [see Warnings and Precautions (5.2)]. oRisk of Infections [see Warnings and Precautions (5.3)]. oRefeeding syndrome [see Warnings and Precautions (5.4)]. oHyperglycemia or hyperosmolar hyperglycemic state [see Warnings and Precautions (5.5)]. oVein damage and thrombosis [see Warnings and Precautions (5.6)]. oHepatobiliary disorders [see Warnings and Precautions (5.7)]. oParenteral Nutrition Associated Liver Disease [see Warnings and Precautions (5.9) ]. oElectrolyte imbalance and fluid overload [see Warnings and Precautions (5.10)]. oDiuresis. oExtravasation. oGlycosuria. oHyperglycemia. oHyperosmolar 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.

CLINICAL PHARMACOLOGY SECTION.


12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action CLINIMIX is used as supplement of nutrition in patients, providing macronutrients (amino acids and dextrose) parenterally.The amino acids provide the structural units that make up proteins and are used to synthesize proteins and other biomolecules or are oxidized to urea and carbon dioxide as source of energy.The administered dextrose is oxidized to carbon dioxide and water, yielding energy.. 12.3 Pharmacokinetics The disposition of infused amino acids and dextrose, are essentially the same as those absorbed from ordinary food.

DESCRIPTION SECTION.


11 DESCRIPTION. CLINIMIX sulfite-free (amino acids in dextrose) injection for intravenous use consists of sterile, nonpyrogenic, hypertonic solutions in dual chamber container.The outlet port chamber contains essential and nonessential amino acids. The formulas for the individual amino acids found in CLINIMIX sulfite-free (amino acids in dextrose) injections are provided in Table 8.Table 8: Formulas for Amino AcidsEssential Amino AcidsLeucine(CH3)2 CHCH2CH (NH2) COOHIsoleucineCH3CH2CH (CH3) CH (NH2) COOHValine(CH3)2 CHCH (NH2) COOHLysine (added as the hydrochloride salt)H2N (CH2)4 CH (NH2) COOHPhenylalanine(C6H5) CH2 CH (NH2) COOHHistidine(C3H3N2) CH2CH (NH2) COOHThreonineCH3CH (OH) CH (NH2) COOMethionineCH3S (CH2)2 CH (NH2) COOHTryptophan(C8H6N) CH2 CH (NH2) COOHNonessential Amino AcidsAlanineCH3CH (NH2) COOHArginineH2NC (NH) NH (CH2)3 CH (NH2) COOHGlycineH2NCH2COOHProline[(CH2)3 NH CH] COOHSerineHOCH2CH (NH2) COOHTyrosine[C6H4 (OH)] CH2CH (NH2) COOHThe injection port chamber contains dextrose. Dextrose, USP, is chemically designated D-glucose, monohydrate (C6H12O6 H2O) and has the following structure:Dextrose is derived from corn.See Table for composition, pH, osmolarity, ionic concentration and caloric content of the admixed product [see Dosage Forms and Strengths (3)]. The dual chamber container is lipid-compatible plastic container (PL 2401 Plastic).CLINIMIX contains no more than 25 mcg/L of aluminum.. Structural Formula Dexrose Hydrous, USP.

DOSAGE & ADMINISTRATION SECTION.


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 oCLINIMIX is available in three port container configuration and two port container configuration.oThree 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. oTwo 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.oTear 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.oInspect 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:oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.oCheck 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.oCheck 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. oLipids 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 19 to 22 gauge needle through the medication port. oCalcium 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)].oInspect the container to ensure precipitates have not formed during the mixing or addition of additives. 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 yellowish streaking or the accumulation of yellowish droplets in the mixed emulsion. Discard the admixture if any of the above are observed.. oCLINIMIX is available in three port container configuration and two port container configuration.oThree 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. oTwo 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.. oThree 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. oTwo 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.. oTear 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.. oInspect 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:oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.oCheck 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.oCheck 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. oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.. oCheck 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.. oCheck 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.. oLipids 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 19 to 22 gauge needle through the medication port. oCalcium 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)].. oInspect the container to ensure precipitates have not formed during the mixing or addition of additives. 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 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 oSet the vent to the closed position on vented intravenous administration set to prevent air embolism.oUse dedicated line without any connections to avoid air embolism.oCLINIMIX is for intravenous infusion only into central or peripheral vein. The choice of 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 central catheter [see Warnings and Precautions (5.6)]. oFor central vein infusion only: CLINIMIX 4.25/10, 5/15, 5/20, 8/10, 8/14oFor central or peripheral vein infusion: CLINIMIX 4.25/5, 6/5oThe solution should be inspected for precipitates before admixing, after admixing, and again before administration.oUse 0.22 micron filter for administration of CLINIMIX. If lipid is also administered, use 1.2 micron filter.oIf 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 plasticizer.. oSet the vent to the closed position on vented intravenous administration set to prevent air embolism.. oUse dedicated line without any connections to avoid air embolism.. oCLINIMIX is for intravenous infusion only into central or peripheral vein. The choice of 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 central catheter [see Warnings and Precautions (5.6)]. oFor central vein infusion only: CLINIMIX 4.25/10, 5/15, 5/20, 8/10, 8/14oFor central or peripheral vein infusion: CLINIMIX 4.25/5, 6/5. oFor central vein infusion only: CLINIMIX 4.25/10, 5/15, 5/20, 8/10, 8/14. oFor central or peripheral vein infusion: CLINIMIX 4.25/5, 6/5. oThe solution should be inspected for precipitates before admixing, after admixing, and again before administration.. oUse 0.22 micron filter for administration of CLINIMIX. If lipid is also administered, use 1.2 micron filter.. oIf 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 plasticizer.. 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 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 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 StorageStorage After Removal of Overwrap: Once removed from the protective overwrap, mixed (peel seal activated) or unmixed (peel seal intact) CLINIMIX solutions may be stored under refrigeration for up to days.Storage Once any Additive is Added:Use promptly after mixing. Any storage with additives should be under refrigeration and limited to 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.. 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 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 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.. 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.. 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.. Figure 1-4. Clinimix Figures 1-4 port Container 2.4 Preparation and Addition of Lipid Emulsion Three Port Container1.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 Container1.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 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 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.. 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.. 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 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.. 2.5 Dosing Considerations oThe dosage of CLINIMIX should be individualized based on the patients 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 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. oCLINIMIX formulations have varying concentrations of protein and carbohydrate; 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.oThe 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.oCLINIMIX 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.oTotal 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.oPrior to administration of CLINIMIX correct severe fluid, electrolyte and acid-base disorders.oMonitor levels of serum potassium during therapy. It may be necessary to add potassium to the CLINIMIX admixture.oLipid emulsion administration should be considered with prolonged use (more than days) of CLINIMIX 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. oThe 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.. oThe dosage of CLINIMIX should be individualized based on the patients 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 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. oCLINIMIX formulations have varying concentrations of protein and carbohydrate; 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.. oThe 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.. oCLINIMIX 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.. oTotal 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.. oPrior to administration of CLINIMIX correct severe fluid, electrolyte and acid-base disorders.. oMonitor levels of serum potassium during therapy. It may be necessary to add potassium to the CLINIMIX admixture.. oLipid emulsion administration should be considered with prolonged use (more than days) of CLINIMIX 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. oThe 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 are shown in Table 1. As indicated on an individual basis, maintenance vitamins, 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 patients 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 Adult DosageCLINIMIX 4.25/5CLINIMIX 4.25/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Fluid (mL/kg/day)19 to 4019 to 4016 to 4016 to 4013 to 3310 to 2510 to 25ProteinProtein 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 1.7(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 (0.13 to 0.32)0.8 to (0.13 to 0.32)0.8 to (0.13 to 0.32)Dextrose (g/kg/day)0.95 to 21.9 to 42.4 to 63.2 to 80.65 to 1.651 to 2.51.4 to 3.5Table 2: Maximum Infusion Rate in Adult Patients Maximum Infusion Rates in Adults PatientsCLINIMIX 4.25/5CLINIMIX 4.25/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Maximum Infusion Rate (mL/kg/hour)2.42.41.671.251.671.31.3Corresponding infusion rateAmino Acid (g/kg/hour)0.1Rate limiting factor 0.1 0.080.060.1 0.1 0.1 Dextrose (g/kg/hour)0.120.240.25 0.25 0.080.130.18. 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 administered as required [see Warnings and Precautions (5.10)].Chronic kidney disease patients with less than nephrotic range proteinuria require 0.8 of protein/kg/day. Chronic kidney disease patients with nephrotic range proteinuria require 0.8g of protein/kg/day plus 1g of protein for each gram of proteinuria. Patients needing dialysis should receive from 1.2 of protein/kg/day up to maximum of 2.5 of protein/kg/day depending on the nutritional status and the dialysis modality. Serum electrolyte levels should be closely monitored. The CLINIMIX 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 container or infused separately. Compatibility of additions should be evaluated by 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 is dosed on the basis of protein provided as amino acids. The recommended dosage, by age group is provided in Tables - 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 Month of Age Recommended CLINIMIX Dosage in Preterm and Term Infants Less than Month of AgeCLINIMIX 4.25/5CLINIMIX 4.2 5/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Infusion Rate Range (mL/kg/hr)2.9 to 3.92.9 to 3.92.5 to 3.32.5 to 3.32.1 to 2.81.6 to 2.11.6 to 2.1Fluid (mL/kg/day)70 to 9470 to 9460 to 7960 to 7950 to 6738.4 to 5038.4 to 50ProteinProtein 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)3.5 to 4.77 to 9.49 to 11.912 to 15.82.5 to 3.43.8 to 55.4 to 7Table 4: Pediatric Patients Month to Less than Year of Age Recommended CLINIMIX Dosage in Pediatric Patients Month to Less than Year of AgeCLINIMIX 4.25/5CLINIMIX 4.25/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Infusion Rate Range (mL/kg/hr)2 to 2.92 to 2.91.7 to 2.51.7 to 2.51.4 to 2.11 to 1.61 to 1.6Fluid (mL/kg/day)48 to 7048 to 7041 to 6041 to 6033.6 to 5024 to 38.424 to 38.4ProteinProtein 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)2.4 to 3.54.8 to 76.1 to 98.2 to 121.7 to 2.52.4 to 3.83.4 to 5.4Table 5: Pediatric Patients Year to Less than 11 Years of Age Recommended CLINIMIX Dosage in Pediatric Patients Year to Less than 11 Years of AgeCLINIMIX 4.25/5CLINIMIX 4.25/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Infusion Rate Range (mL/kg/hr)1 to 21 to 20.8 to 1.70.8 to 1.70.7 to 1.40.5 to 10.5 to 1Fluid (mL/kg/day)24 to 4824 to 4819 to 4119 to 4116.8 to 33.612 to 2412 to 24ProteinProtein 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)1.2 to 2.42.4 to 4.82.9 to 6.13.8 to 8.20.8 to 1.71.2 to 2.41.7 to 3.4Table 6: Pediatric Patients 11 Years to 17 Years of Age Recommended CLINIMIX Dosage in Pediatric Patients 11 Years to 17 Years of AgeCLINIMIX 4.25/5CLINIMIX 4.25/10CLINIMIX 5/15CLINIMIX 5/20CLINIMIX 6/5CLINIMIX 8/10CLINIMIX 8/14Infusion Rate Range (mL/kg/hr)0.8 to 1.50.8 to 1.50.7 to 1.30.7 to 1.30.6 to 10.4 to 0.80.4 to 0.8Fluid (mL/kg/day)19 to 3619 to 3617 to 3117 to 3114.4 to 249.6 to 19.29.6 to 19.2ProteinProtein 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 to 1.81.9 to 3.62.5 to 4.73.4 to 6.20.7 to 1.21 to 1.91.4 to.2.7. 2.9 Discontinuation of CLINIMIX To reduce the risk of hypoglycemia after discontinuation, gradual decrease in flow rate in the last hour of infusion should be considered.

DOSAGE FORMS & STRENGTHS SECTION.


3 DOSAGE FORMS AND STRENGTHS. CLINIMIX injection is available in 1000 mL and 2000 mL dual chamber containers. The individual chambers contain essential and nonessential amino acids and dextrose. Table describes the individual components of CLINIMIX.Table INGREDIENTS PER 100mL OF CLINIMIXStrength of CLINIMIXCLINIMIX 4.25/5 sulfite-free(4.25% Amino Acid in 5% Dextrose) InjectionCLINIMIX4.25/10 sulfite-free(4.25% Amino Acid in 10% Dextrose) InjectionCLINIMIX5/15 sulfite-free(5% Amino Acid in 15% Dextrose) InjectionCLINIMIX5/20 sulfite-free(5% Amino Acid in 20% Dextrose) InjectionCLINIMIX 6/5 sulfite-free(6% Amino Acid in 5% Dextrose) InjectionCLINIMIX 8/10 sulfite-free(8% Amino Acid in 10% Dextrose) InjectionCLINIMIX 8/14 sulfite-free(8% Amino Acid in 14% Dextrose) InjectionDextrose Hydrous, USP (g/100 mL)510152051014Amino Acids (g/100 mL)4.254.2555688Total Nitrogen (mg/100 mL)70270282682699013201320 Essential Amino Acids(mg/100 mL)Leucine 311311365365438584584Isoleucine 255255300300360480480Valine 247247290290348464464Lysine (added as the hydrochloride salt) 247247290290348464464Phenylalanine 238238280280336448448Histidine 204204240240288384384Threonine 179179210210252336336Methionine 170170200200240320320Tryptophan 77779090108144144 Nonessential Amino Acids(mg/100 mL)Alanine 88088010351035124216561656Arginine 489489575575690920920Glycine 438438515515618824824Proline 289289340340408544544Serine 213213250250300400400Tyrosine 17172020243232 AnionProfile(mEq/L)Balanced by ions from amino acids. AcetateDerived from glacial acetic acid (for pH adjustment). 37374242537171ChlorideContributed by lysine hydrochloride and hydrochloric acid (for pH adjustment). 17172020243232pHpH of sulfite-free amino acid injection in the outlet port chamber may be adjusted with glacial acetic acid and pH of dextrose injection port chamber may be adjusted with hydrochloric acid.(Range)6.0(4.5 to 7.0)6.0(4.5 to 7.0)6.0(4.5 to 7.0)6.0(4.5 to 7.0)6.0(4.5 to 7.0)6.0(4.5 to 7.0)6.0(4.5 to 7.0)Osmolarity (mOsmol/L) (calc)6759301255150585013081520Caloric Content(kcal/L)From Dextrose170340510680170343477From Amino Acids170170200200240320320TOTAL (Dextrose and Amino Acids)340510710880410663797. Essential Amino Acids(mg/100 mL). Nonessential Amino Acids(mg/100 mL). AnionProfile(mEq/L)Balanced by ions from amino acids. CLINIMIX injection is available in multiple strengths. See full prescribing information for detailed description of each formulation. (3, 11).

GERIATRIC USE SECTION.


8.5 Geriatric Use Clinical studies of CLINIMIX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from other younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

HOW SUPPLIED SECTION.


16 HOW SUPPLIED/STORAGE AND HANDLING CLINIMIX (amino acids in dextrose) injection (sulfite-free) is available in 1000 mL and 2000 mL volumes (See Table 9).Table 9: CLINIMIX Formulations After mixing, the product represents 1000 mL Code and NDC Number 2000 mL Code and NDC Number CLINIMIX 4.25/5 sulfite-free(4.25% Amino Acid in 5% Dextrose) Injection Code 2B7726NDC 0338-1133-03 Code 2B7704NDC 0338-1089-04 CLINIMIX 4.25/10 sulfite-free(4.25% Amino Acid in 10% Dextrose) Injection Code 2B7727NDC 0338-1134-03 Code 2B7705NDC 0338-1091-04 CLINIMIX 5/15 sulfite-free(5% Amino Acid in 15% Dextrose) Injection Code 2B7730NDC 0338-1137-03 Code 2B7709NDC 0338-1099-04 CLINIMIX 5/20 sulfite-free(5% Amino Acid in 20% Dextrose) Injection Code 2B7731NDC 0338-1138-03 Code 2B7710NDC 0338-1101-04 CLINIMIX 6/5 sulfite-free(6% Amino Acid in 5% Dextrose) Injection Code EADB9913NDC 0338-0198-06 CLINIMIX 8/10 sulfite-free(8% Amino Acid in 10% Dextrose) Injection Code EADB9933NDC 0338-0188-06 Code EADB9935NDC 0338-0194-04 CLINIMIX 8/14 sulfite-free(8% Amino Acid in 14% Dextrose) Injection Code EADB9953NDC 0338-0180-06 Code EADB9955NDC 0338-0184-04Minimize exposure of CLINIMIX to heat and avoid excessive heat. Protect from freezing. Store CLINIMIX at room temperature (25C/77F) (may briefly store at up to 40C/104F). Refrigerated storage is limited to days once the protective overwrap has been opened.Do not use if the protective overwrap has been previously opened or damaged.For storage of admixed solutions see Dosage and Administration (2.3, 2.4).. After mixing, the product represents. 1000 mL Code and NDC Number. 2000 mL Code and NDC Number. CLINIMIX 4.25/5 sulfite-free(4.25% Amino Acid in 5% Dextrose) Injection. Code 2B7726NDC 0338-1133-03. Code 2B7704NDC 0338-1089-04. CLINIMIX 4.25/10 sulfite-free(4.25% Amino Acid in 10% Dextrose) Injection. Code 2B7727NDC 0338-1134-03. Code 2B7705NDC 0338-1091-04. CLINIMIX 5/15 sulfite-free(5% Amino Acid in 15% Dextrose) Injection. Code 2B7730NDC 0338-1137-03. Code 2B7709NDC 0338-1099-04. CLINIMIX 5/20 sulfite-free(5% Amino Acid in 20% Dextrose) Injection. Code 2B7731NDC 0338-1138-03. Code 2B7710NDC 0338-1101-04. CLINIMIX 6/5 sulfite-free(6% Amino Acid in 5% Dextrose) Injection. Code EADB9913NDC 0338-0198-06. CLINIMIX 8/10 sulfite-free(8% Amino Acid in 10% Dextrose) Injection. Code EADB9933NDC 0338-0188-06. Code EADB9935NDC 0338-0194-04. CLINIMIX 8/14 sulfite-free(8% Amino Acid in 14% Dextrose) Injection. Code EADB9953NDC 0338-0180-06. Code EADB9955NDC 0338-0184-04.

INFORMATION FOR PATIENTS SECTION.


17 PATIENT COUNSELING INFORMATION. Inform patients, caregivers, or home healthcare providers of the following risks of CLINIMIX:oPulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]oHypersensitivity reactions [see Warnings and Precautions (5.2)]oRisk of Infections [see Warnings and Precautions (5.3)]oRefeeding syndrome [see Warnings and Precautions (5.4)]oHyperglycemia or hyperosmolar hyperglycemic state [see Warnings and Precautions (5.5)]oVein damage and thrombosis [see Warnings and Precautions (5.6)]oHepatobiliary disorders [see Warnings and Precautions (5.7)]oAluminum toxicity [see Warnings and Precautions (5.8)]oParenteral Nutrition Associated Liver Disease (PNULLLD) [see Warnings and Precautions (5.9)]oElectrolyte imbalance and fluid overload [see Warnings and Precautions (5.10)]. oPulmonary embolism due to pulmonary vascular precipitates [see Warnings and Precautions (5.1)]. oHypersensitivity reactions [see Warnings and Precautions (5.2)]. oRisk of Infections [see Warnings and Precautions (5.3)]. oRefeeding syndrome [see Warnings and Precautions (5.4)]. oHyperglycemia or hyperosmolar hyperglycemic state [see Warnings and Precautions (5.5)]. oVein damage and thrombosis [see Warnings and Precautions (5.6)]. oHepatobiliary disorders [see Warnings and Precautions (5.7)]. oAluminum toxicity [see Warnings and Precautions (5.8)]. oParenteral Nutrition Associated Liver Disease (PNULLLD) [see Warnings and Precautions (5.9)]. oElectrolyte imbalance and fluid overload [see Warnings and Precautions (5.10)].

LACTATION SECTION.


8.2 Lactation Risk SummaryIt is not known whether CLINIMIX is present in human milk. There are no data on the effects of CLINIMIX on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for CLINIMIX and any potential adverse effects on the breastfed child from CLINIMIX or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.


12.1 Mechanism of Action CLINIMIX is used as supplement of nutrition in patients, providing macronutrients (amino acids and dextrose) parenterally.The amino acids provide the structural units that make up proteins and are used to synthesize proteins and other biomolecules or are oxidized to urea and carbon dioxide as source of energy.The administered dextrose is oxidized to carbon dioxide and water, yielding energy.

OVERDOSAGE SECTION.


10 OVERDOSAGE. An increased infusion rate of CLINIMIX cause hyperglycemia, hyperosmolality, and adverse effects on water and electrolyte balance [see Warnings and Precautions (5.5, 5.10)]. Severe hyperglycemia and severe dilutional hyponatremia, and their complications, can be fatal.Discontinue infusion and institute appropriate corrective measures in the event of overhydration or solute overload during therapy, with particular attention to respiratory and cardiovascular systems. For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PACKAGE LABEL PRINCIPAL DISPLAY PANEL. Container Label LOT EXP2B7727 NDC 0338-1134-03CLINIMIX4.25/10SULFITE-FREE(4.25% Amino Acidsin 10% Dextrose)Injection500 mL INJECTION PORT CHAMBER20% Dextrose Injection USP500 mL OUTLET PORT CHAMBER8.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXEDINJECTIONDEXTROSE HYDROUS USP 10 gESSENTIAL AMINO ACIDSLEUCINE 311 mgISOLEUCINE 255 mgVALINE 247 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 247 mgPHENYLALANINE 238 mgHISTIDINE 204 mgTHREONINE 179 mgMETHIONINE 170 mgTRYPTOPHAN 77 mgNONESSENTIAL AMINO ACIDSALANINE 880 mgARGININE 489 mgGLYCINE 438 mgPROLINE 289 mgSERINE 213 mgTYROSINE 17 mgmEq/LACETATE 37CHLORIDE 17BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7726 NDC 0338-1133-03CLINIMIX4.25/5SULFITE-FREE(4.25% Amino Acidsin 5% Dextrose)Injection500 mL INJECTION PORT CHAMBER10% Dextrose Injection USP500 mL OUTLET PORT CHAMBER8.5% Amino Acid InjectionACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXEDINJECTIONDEXTROSE HYDROUS USP gESSENTIAL AMINO ACIDSLEUCINE 311 mgISOLEUCINE 255 mgVALINE 247 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 247 mgPHENYLALANINE 238 mgHISTIDINE 204 mgTHREONINE 179 mgMETHIONINE 170 mgTRYPTOPHAN 77 mgNONESSENTIAL AMINO ACIDSALANINE 880 mgARGININE 489 mgGLYCINE 438 mgPROLINE 289 mgSERINE 213 mgTYROSINE 17 mgmEq/LACETATE 37CHLORIDE 17BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7704 NDC 0338-1089-04CLINIMIX 4.25/5SULFITE-FREE(4.25% Amino Acidin 5% Dextrose)Injection1000 mL INJECTION PORT CHAMBER10% Dextrose Injection USP1000 mL OUTLET PORT CHAMBER8.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP gESSENTIAL AMINO ACIDSLEUCINE 311 mgISOLEUCINE 255 mgVALINE 247 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 247 mgPHENYLALANINE 238 mgHISTIDINE 204 mgTHREONINE 179 mgMETHIONINE 170 mgTRYPTOPHAN 77 mgNONESSENTIAL AMINO ACIDSALANINE 880 mgARGININE 489 mgGLYCINE 438 mgPROLINE 289 mgSERINE 213 mgTYROSINE 17 mgmEq/LACETATE 37CHLORIDE 17BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer LabelLOT EXP2B7705 NDC 0338-1091-04CLINIMIX 4.25/10SULFITE-FREE(4.25% Amino Acidin 10% Dextrose)Injection1000 mL INJECTION PORT CHAMBER20% Dextrose Injection USP1000 mL OUTLET PORT CHAMBER8.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 10 gESSENTIAL AMINO ACIDSLEUCINE 311 mgISOLEUCINE 255 mgVALINE 247 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 247 mgPHENYLALANINE 238 mgHISTIDINE 204 mgTHREONINE 179 mgMETHIONINE 170 mgTRYPTOPHAN 77 mgNONESSENTIAL AMINO ACIDSALANINE 880 mgARGININE 489 mgGLYCINE 438 mgPROLINE 289 mgSERINE 213 mgTYROSINE 17 mgmEq/LACETATE 37CHLORIDE 17BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7730 NDC 0338-1137-03CLINIMIX 5/15SULFITE-FREE(5% Amino Acidin 15% Dextrose)Injection500 mL INJECTION PORT CHAMBER30% Dextrose Injection USP500 mL OUTLET PORT CHAMBER10% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 15 gESSENTIAL AMINO ACIDSLEUCINE 365 mgISOLEUCINE 300 mgVALINE 290 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 290 mgPHENYLALANINE 280 mgHISTIDINE 240 mgTHREONINE 210 mgMETHIONINE 200 mgTRYPTOPHAN 90 mgNONESSENTIAL AMINO ACIDSALANINE 1035 mgARGININE 575 mgGLYCINE 515 mgPROLINE 340 mgSERINE 250 mgTYROSINE 20 mgmEq/LACETATE 42CHLORIDE 20BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7709 NDC 0338-1099-04CLINIMIX 5/15SULFITE-FREE(5% Amino Acidin 15% Dextrose)Injection1000 mL INJECTION PORT CHAMBER30% Dextrose Injection USP1000 mL OUTLET PORT CHAMBER10% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 15 gESSENTIAL AMINO ACIDSLEUCINE 365 mgISOLEUCINE 300 mgVALINE 290 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 290 mgPHENYLALANINE 280 mgHISTIDINE 240 mgTHREONINE 210 mgMETHIONINE 200 mgTRYPTOPHAN 90 mgNONESSENTIAL AMINO ACIDSALANINE 1035 mgARGININE 575 mgGLYCINE 515 mgPROLINE 340 mgSERINE 250 mgTYROSINE 20 mgmEq/LACETATE 42CHLORIDE 20BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7731 NDC 0338-1138-03CLINIMIX 5/SULFITE-FREE(5% Amino Acidin 20% Dextrose)Injection500 mL INJECTION PORT CHAMBER40% Dextrose Injection USP500 mL OUTLET PORT CHAMBER10% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 20 gESSENTIAL AMINO ACIDSLEUCINE 365 mgISOLEUCINE 300 mgVALINE 290 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 290 mgPHENYLALANINE 280 mgHISTIDINE 240 mgTHREONINE 210 mgMETHIONINE 200 mgTRYPTOPHAN 90 mgNONESSENTIAL AMINO ACIDSALANINE 1035 mgARGININE 575 mgGLYCINE 515 mgPROLINE 340 mgSERINE 250 mgTYROSINE 20 mgmEq/LACETATE 42CHLORIDE 20BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USAContainer Label LOT EXP2B7710 NDC 0338-1101-04CLINIMIX 5/20SULFITE-FREE(5% Amino Acidin 20% Dextrose)Injection1000 mL INJECTION PORT CHAMBER40% Dextrose Injection USP1000 mL OUTLET PORT CHAMBER10% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ONULLCTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITYAND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 20 gESSENTIAL AMINO ACIDSLEUCINE 365 mgISOLEUCINE 300 mgVALINE 290 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 290 mgPHENYLALANINE 280 mgHISTIDINE 240 mgTHREONINE 210 mgMETHIONINE 200 mgTRYPTOPHAN 90 mgNONESSENTIAL AMINO ACIDSALANINE 1035 mgARGININE 575 mgGLYCINE 515 mgPROLINE 340 mgSERINE 250 mgTYROSINE 20 mgmEq/LACETATE 42CHLORIDE 20BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACIDSTERILESINGLE DOSE CONTAINERROOM TEMPERATURE (25C/77F)AVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxterBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN USA1000 mLNDC 0338-0198-01CLINIMIX 6/5SULFITE-FREE(6% Amino Acidin 5% Dextrose)Injection400 mL INJECTION PORT CHAMBER12.5% Dextrose Injection USP600 mL OUTLET PORT CHAMBER10% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHTLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ON ACTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSONCE OVERWRAP IS OPENEDA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYEADB9913EXPCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP g ESSENTIAL AMINO ACIDS LEUCINE 438 mgISOLEUCINE 360 mgVALINE 348 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 348 mgPHENYLALANINE 336 mgHISTIDINE 288 mgTHREONINE 252 mgMETHIONINE 240 mgTRYPTOPHAN 108 mg NONESSENTIAL AMINO ACIDS ALANINE 1242 mgARGININE 690 mgGLYCINE 618 mgPROLINE 408 mgSERINE 300 mgTYROSINE 24 mg mEq/L ACETATE 53CHLORIDE 24BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACID AND HYDROCHLORIC ACIDSTERILESINGLE DOSE CONTAINERSTORE AT ROOM TEMPERATURE (25oC/77oF) IN UNOPENED OVERWRAPAVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxter LogoBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN BELGIUMLOTBE-35-04-0401000 mLNDC 0338-0188-01CLINIMIX 8/10SULFITE-FREE(8% Amino Acidin 10% Dextrose)Injection360 mL INJECTION PORT CHAMBER28% Dextrose Injection USP640 mL OUTLET PORT CHAMBER12.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHTLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ON ACTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSONCE OVERWRAP IS OPENEDA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYEADB9933EXPCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 10 ESSENTIAL AMINO ACIDS LEUCINE 584 mgISOLEUCINE 480 mgVALINE 464 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 464 mgPHENYLALANINE 448 mgHISTIDINE 384 mgTHREONINE 336 mgMETHIONINE 320 mgTRYPTOPHAN 144 mg NONESSENTIAL AMINO ACIDS ALANINE 1656 mgARGININE 920 mgGLYCINE 824 mgPROLINE 544 mgSERINE 400 mgTYROSINE 32 mg mEq/L ACETATE 71CHLORIDE 32BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACID AND HYDROCHLORIC ACIDSTERILESINGLE DOSE CONTAINERSTORE AT ROOM TEMPERATURE (25oC/77oF) IN UNOPENED OVERWRAPAVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxter LogoBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN BELGIUMLOTBE-35-04-0412000 mLNDC 0338-0194-01CLINIMIX 8/10SULFITE-FREE(8% Amino Acidin 10% Dextrose)Injection720 mL INJECTION PORT CHAMBER28% Dextrose Injection USP1280 mL OUTLET PORT CHAMBER12.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHTLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ON ACTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSONCE OVERWRAP IS OPENEDA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYEADB9935ExpCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 10 ESSENTIAL AMINO ACIDS LEUCINE 584 mgISOLEUCINE 480 mgVALINE 464 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 464 mgPHENYLALANINE 448 mgHISTIDINE 384 mgTHREONINE 336 mgMETHIONINE 320 mgTRYPTOPHAN 144 mg NONESSENTIAL AMINO ACIDS ALANINE 1656 mgARGININE 920 mgGLYCINE 824 mgPROLINE 544 mgSERINE 400 mgTYROSINE 32 mg mEq/L ACETATE 71CHLORIDE 32BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACID AND HYDROCHLORIC ACIDSTERILESINGLE DOSE CONTAINERSTORE AT ROOM TEMPERATURE (25oC/77oF) IN UNOPENED OVERWRAPAVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxter LogoBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN BELGIUMLotBE-35-04-0451000 mLNDC 0338-0180-01CLINIMIX 8/14SULFITE-FREE(8% Amino Acidin 14% Dextrose)Injection360 mL INJECTION PORT CHAMBER39% Dextrose Injection USP640 mL OUTLET PORT CHAMBER12.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHTLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ON ACTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 1000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSONCE OVERWRAP IS OPENEDA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYEADB9953EXPCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 14 ESSENTIAL AMINO ACIDS LEUCINE 584 mgISOLEUCINE 480 mgVALINE 464 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 464 mgPHENYLALANINE 448 mgHISTIDINE 384 mgTHREONINE 336 mgMETHIONINE 320 mgTRYPTOPHAN 144 mg NONESSENTIAL AMINO ACIDS ALANINE 1656 mgARGININE 920 mgGLYCINE 824 mgPROLINE 544 mgSERINE 400 mgTYROSINE 32 mg mEq/L ACETATE 71CHLORIDE 32BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACID AND HYDROCHLORIC ACIDSTERILESINGLE DOSE CONTAINERSTORE AT ROOM TEMPERATURE (25oC/77oF) IN UNOPENED OVERWRAPAVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxter LogoBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN BELGIUMLOTBE-35-04-0432000 mLNDC 0338-0184-01CLINIMIX 8/14SULFITE-FREE(8% Amino Acidin 14% Dextrose)Injection720 mL INJECTION PORT CHAMBER39% Dextrose Injection USP1280 mL OUTLET PORT CHAMBER12.5% Amino Acid InjectionRx OnlyACTIVATE SEAL ANDMIX THOROUGHTLY BEFORE USESEE PRESCRIBING INFORMATION FOR INSTRUCTIONS ON ACTIVATIONULLFTER MIXING THE PRODUCT REPRESENTS 2000 mLREFRIGERATED STORAGE IS LIMITED TO DAYSONCE OVERWRAP IS OPENEDA SLIGHT YELLOW COLOR DOES NOT ALTER THE QUALITY AND EFFICACY OF THIS PRODUCTASK PHARMACIST ABOUT ADDITIVE COMPATIBILITYEADB9955ExpCONTENTS OF EACH 100 mL OF THE ADMIXED INJECTIONDEXTROSE HYDROUS USP 14 ESSENTIAL AMINO ACIDS LEUCINE 584 mgISOLEUCINE 480 mgVALINE 464 mgLYSINE (ADDED AS THEHYDROCHLORIDE SALT) 464 mgPHENYLALANINE 448 mgHISTIDINE 384 mgTHREONINE 336 mgMETHIONINE 320 mgTRYPTOPHAN 144 mg NONESSENTIAL AMINO ACIDS ALANINE 1656 mgARGININE 920 mgGLYCINE 824 mgPROLINE 544 mgSERINE 400 mgTYROSINE 32 mg mEq/L ACETATE 71CHLORIDE 32BALANCED BY IONS FROM AMINO ACIDSpH ADJUSTED WITH GLACIAL ACETIC ACID AND HYDROCHLORIC ACIDSTERILESINGLE DOSE CONTAINERSTORE AT ROOM TEMPERATURE (25oC/77oF) IN UNOPENED OVERWRAPAVOID EXCESSIVE HEATPROTECT FROM FREEZINGSEE PRESCRIBING INFORMATIONBaxter LogoBAXTER HEALTHCARE CORPORATIONDEERFIELD IL 60015 USAMADE IN BELGIUMLotBE-35-04-047. Representative Container Label 0338-1134. Representative Container Label 0338-1133-03. Representative Container Label 0338-1089-04. Representative Container Label 0338-1091-04. Representative Container 0338-1137-03. Representative Container Label 0338-1099-04. Representative Container Label 0338-1138-03. Representative Container Label 0338-1101-04. Clinimix Representative Container Label 0338-0198-01. Clinimix Representative Container Label 0338-0188-01. Clinimix Representative Container Label 0338-0194-01. Clinimix Representative Container Label 0338-0180-01. Clinimix Representative Container Label 0338-0184-01.

PEDIATRIC USE SECTION.


8.4 Pediatric Use Safety and effectiveness of CLINIMIX in pediatric patients have not been established by adequate and well-controlled studies. Use of dextrose, amino acid infusions and electrolytes in pediatric patients is based on clinical practice [see Dosage and Administration (2.8)].Newborns, especially those born premature and with low birth weight, are at increased risk of developing hypo or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death. Plasma electrolyte concentrations should be closely monitored in the pediatric population as this population may have impaired ability to regulate fluids and electrolytes.Because of immature renal function, preterm infants receiving prolonged treatment with CLINIMIX may be at risk of aluminum toxicity [see Warnings and Precautions (5.8)].Patients, including pediatric patients, may be at risk for Parenteral Nutrition Associated Liver Disease (PNULLLD) [see Warnings and Precautions (5.9)].Hyperammonemia is of special significance in infants (birth to two years). This reaction appears to be related to deficiency of the urea cycle amino acids of genetic or product origin. It is essential that blood ammonia be measured frequently in infants [see Warnings and Precautions (5.7) ].

PHARMACOKINETICS SECTION.


12.3 Pharmacokinetics The disposition of infused amino acids and dextrose, are essentially the same as those absorbed from ordinary food.

PREGNULLNCY SECTION.


8.1 Pregnancy. Risk SummaryThere are no adequate or well-controlled studies in pregnant women with CLINIMIX. Additionally, animal reproduction studies have not been conducted with amino acids and electrolytes and dextrose. It is not known whether CLINIMIX can cause fetal harm when administered to pregnant woman.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. However, the estimated background risk in the U.S. general population of major birth defects is to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Clinical ConsiderationsDisease-Associated Maternal and/or Embryo-Fetal RiskBased on clinical practice guidelines, parenteral nutrition should be considered in cases of severe maternal malnutrition where nutritional requirements cannot be fulfilled by the enteral route because of the risks to the fetus associated with severe malnutrition, such as preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality.

RECENT MAJOR CHANGES SECTION.


Dosage and Administration, Instructions for Use (2.3, 2.7) 04/2021Warnings and Precautions (5.5) 04/2021Dosage and Administration (2.1, 2.3, 2.4, 2.6, 2.8) 09/2020. Dosage and Administration, Instructions for Use (2.3, 2.7) 04/2021Warnings and Precautions (5.5) 04/2021Dosage and Administration (2.1, 2.3, 2.4, 2.6, 2.8) 09/2020.

SPL UNCLASSIFIED SECTION.


2.1 Preparation Prior to Administration oCLINIMIX is available in three port container configuration and two port container configuration.oThree 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. oTwo 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.oTear 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.oInspect 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:oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.oCheck 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.oCheck 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. oLipids 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 19 to 22 gauge needle through the medication port. oCalcium 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)].oInspect the container to ensure precipitates have not formed during the mixing or addition of additives. 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 yellowish streaking or the accumulation of yellowish droplets in the mixed emulsion. Discard the admixture if any of the above are observed.. oCLINIMIX is available in three port container configuration and two port container configuration.oThree 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. oTwo 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.. oThree 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. oTwo 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.. oTear 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.. oInspect 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:oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.oCheck 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.oCheck 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. oIf the outlet or additive port protectors are damaged, detached, or not present, discard container as solution path sterility may be impaired.. oCheck 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.. oCheck 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.. oLipids 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 19 to 22 gauge needle through the medication port. oCalcium 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)].. oInspect the container to ensure precipitates have not formed during the mixing or addition of additives. 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 yellowish streaking or the accumulation of yellowish droplets in the mixed emulsion. Discard the admixture if any of the above are observed.

USE IN SPECIFIC POPULATIONS SECTION.


8 USE IN SPECIFIC POPULATIONS. Pediatric Use: increased risk of hypoglycemia/hyperglycemia: monitor serum glucose concentrations. (8.4). 8.1 Pregnancy. Risk SummaryThere are no adequate or well-controlled studies in pregnant women with CLINIMIX. Additionally, animal reproduction studies have not been conducted with amino acids and electrolytes and dextrose. It is not known whether CLINIMIX can cause fetal harm when administered to pregnant woman.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. However, the estimated background risk in the U.S. general population of major birth defects is to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Clinical ConsiderationsDisease-Associated Maternal and/or Embryo-Fetal RiskBased on clinical practice guidelines, parenteral nutrition should be considered in cases of severe maternal malnutrition where nutritional requirements cannot be fulfilled by the enteral route because of the risks to the fetus associated with severe malnutrition, such as preterm delivery, low birth weight, intrauterine growth restriction, congenital malformations and perinatal mortality.. 8.2 Lactation Risk SummaryIt is not known whether CLINIMIX is present in human milk. There are no data on the effects of CLINIMIX on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for CLINIMIX and any potential adverse effects on the breastfed child from CLINIMIX or from the underlying maternal condition.. 8.4 Pediatric Use Safety and effectiveness of CLINIMIX in pediatric patients have not been established by adequate and well-controlled studies. Use of dextrose, amino acid infusions and electrolytes in pediatric patients is based on clinical practice [see Dosage and Administration (2.8)].Newborns, especially those born premature and with low birth weight, are at increased risk of developing hypo or hyperglycemia and therefore need close monitoring during treatment with intravenous glucose solutions to ensure adequate glycemic control in order to avoid potential long term adverse effects. Hypoglycemia in the newborn can cause prolonged seizures, coma and brain damage. Hyperglycemia has been associated with intraventricular hemorrhage, late onset bacterial and fungal infection, retinopathy of prematurity, necrotizing enterocolitis, bronchopulmonary dysplasia, prolonged length of hospital stay, and death. Plasma electrolyte concentrations should be closely monitored in the pediatric population as this population may have impaired ability to regulate fluids and electrolytes.Because of immature renal function, preterm infants receiving prolonged treatment with CLINIMIX may be at risk of aluminum toxicity [see Warnings and Precautions (5.8)].Patients, including pediatric patients, may be at risk for Parenteral Nutrition Associated Liver Disease (PNULLLD) [see Warnings and Precautions (5.9)].Hyperammonemia is of special significance in infants (birth to two years). This reaction appears to be related to deficiency of the urea cycle amino acids of genetic or product origin. It is essential that blood ammonia be measured frequently in infants [see Warnings and Precautions (5.7) ]. 8.5 Geriatric Use Clinical studies of CLINIMIX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from other younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or drug therapy.

WARNINGS AND PRECAUTIONS SECTION.


5 WARNINGS AND PRECAUTIONS. oPulmonary Embolism due to Pulmonary Vascular Precipitates: if signs of pulmonary distress occur, stop the infusion and initiate medical evaluation. (5.1)oHypersensitivity Reactions: monitor for signs and symptoms and discontinue infusion if reactions occur. (5.2)oRisk of Infections, Refeeding Complications, and Hyperglycemia or Hyperosmolar Hyperglycemic State: monitor for signs and symptoms; monitor laboratory parameters. (5.3, 5.4, 5.5)oVein Damage and Thrombosis: solutions with osmolarity of >= 900 mOsm/L must be infused through central catheter. (2.2, 5.6)oHepatobiliary Disorders: monitor liver function parameters and ammonia levels. (5.7)oAluminum Toxicity: increased risk in patients with impaired kidney function, including preterm infants. (5.8, 8.4)oParenteral Nutrition Associated Liver Disease: increased risk in patients who receive parenteral nutrition for extended periods of time, especially preterm infants; monitor liver function tests, if abnormalities occur consider discontinuation or dosage reduction. (5.9, 8.4)oElectrolyte Imbalance and Fluid Overload: patients with cardiac insufficiency or kidney disease may require adjustment of fluid, protein and electrolyte content. (5.10, 8.4). oPulmonary Embolism due to Pulmonary Vascular Precipitates: if signs of pulmonary distress occur, stop the infusion and initiate medical evaluation. (5.1). oHypersensitivity Reactions: monitor for signs and symptoms and discontinue infusion if reactions occur. (5.2). oRisk of Infections, Refeeding Complications, and Hyperglycemia or Hyperosmolar Hyperglycemic State: monitor for signs and symptoms; monitor laboratory parameters. (5.3, 5.4, 5.5). oVein Damage and Thrombosis: solutions with osmolarity of >= 900 mOsm/L must be infused through central catheter. (2.2, 5.6). oHepatobiliary Disorders: monitor liver function parameters and ammonia levels. (5.7). oAluminum Toxicity: increased risk in patients with impaired kidney function, including preterm infants. (5.8, 8.4). oParenteral Nutrition Associated Liver Disease: increased risk in patients who receive parenteral nutrition for extended periods of time, especially preterm infants; monitor liver function tests, if abnormalities occur consider discontinuation or dosage reduction. (5.9, 8.4). oElectrolyte Imbalance and Fluid Overload: patients with cardiac insufficiency or kidney disease may require adjustment of fluid, protein and electrolyte content. (5.10, 8.4). 5.1 Pulmonary Embolism due to Pulmonary Vascular Precipitates. Pulmonary vascular precipitates causing pulmonary vascular emboli and pulmonary distress have been reported in patients receiving parenteral nutrition. In some cases, fatal outcomes due to pulmonary embolism have occurred. CLINIMIX contains no added phosphorus. Patients, especially those with hypophosphatemia, may require the addition of phosphate. To prevent hypocalcemia, calcium supplementation should always accompany phosphate administration. Excessive addition of calcium and phosphate increases the risk of the formation of calcium phosphate precipitates. Precipitates have been reported even in the absence of phosphate salt in the solution. Precipitation following passage through an in-line filter and suspected in vivo precipitate formation has also been reported. If signs of pulmonary distress occur, stop the infusion and initiate medical evaluation. In addition to inspection of the solution [see Dosage and Administration (2.1, 2.2, 2.3, 2.4)], the infusion set and catheter should also periodically be checked for precipitates.. 5.2 Hypersensitivity Reactions. Hypersensitivity/infusion reactions including anaphylaxis have been reported with CLINIMIX. Stop infusion immediately and treat patient accordingly if any signs or symptoms of hypersensitivity reaction develop. Signs or symptoms may include: hypotension, hypertension, peripheral cyanosis, tachycardia, dyspnea, vomiting, nausea, urticaria, rash, pruritus, erythema, hyperhidrosis, pyrexia, and chills.. 5.3 Risk of Infections. Patients who require parenteral nutrition are at high risk of infections because the nutritional components of these solutions can support microbial growth. Infection and sepsis may also occur as result of the use of intravenous catheters to administer parenteral nutrition.The risk of infection is increased in patients with malnutrition-associated immunosuppression, hyperglycemia exacerbated by dextrose infusion, long-term use and poor maintenance of intravenous catheters, or immunosuppressive effects of other concomitant conditions, drugs, or other components of the parenteral formulation (e.g., lipid emulsion). To decrease the risk of infection, ensure aseptic technique in catheter placement and maintenance, as well as aseptic technique in the preparation and administration of the nutritional formula. Monitor for signs and symptoms (including fever and chills) of early infections, including laboratory test results (including leukocytosis and hyperglycemia) and frequent checks of the parenteral access device and insertion site for edema, redness and discharge.. 5.4 Refeeding Syndrome. Refeeding severely undernourished patients may result in refeeding syndrome, characterized by the intracellular shift of potassium, phosphorus, and magnesium as the patient becomes anabolic. Thiamine deficiency and fluid retention may also develop. To prevent these complications, monitor severely undernourished patients and slowly increase nutrient intakes.. 5.5 Hyperglycemia or Hyperosmolar Hyperglycemic State. When using CLINIMIX in patients with diabetes mellitus, impaired glucose tolerance may worsen hyperglycemia. Administration of dextrose at rate exceeding the patients utilization rate may lead to hyperglycemia, coma, and death. Patients with dehydration, resulting in transient reduction in glomerular filtration rate and pre-renal azotemia, may be greater risk of developing hyperosmolar hyperglycemic state. Monitor blood glucose levels and treat hyperglycemia to maintain optimum levels while administering CLINIMIX. Insulin may be administered or adjusted to maintain optimal blood glucose levels during CLINIMIX administration.. 5.6 Vein Damage and Thrombosis. Solutions with osmolarity of 900 mOsm/L or greater must be infused through central catheter. CLINIMIX solutions containing more than 5% dextrose have an osmolarity greater than or equal to 900 mOsm/L. CLINIMIX 4.25/10, 5/15, 5/20, 8/10 and 8/14 are indicated for administration into central vein only, such as the superior vena cava [see Dosage and Administration (2.2)]. The infusion of hypertonic nutrient injections into peripheral vein may result in vein irritation, vein damage, and/or thrombosis.CLINIMIX 4.25/5 and 6/5 are indicated for peripheral administration, or may be infused into central vein [see Dosage and Administration (2.2)]. The primary complication of peripheral access is venous thrombophlebitis, which manifests as pain, erythema, tenderness or palpable cord. Remove the catheter as soon as possible, if thrombophlebitis develops.. 5.7 Hepatobiliary Disorders. Hepatobiliary disorders are known to develop in some patients without preexisting liver disease who receive parenteral nutrition, including cholecystitis, cholelithiasis, cholestasis, hepatic steatosis, fibrosis and cirrhosis, possibly leading to hepatic failure. The etiology of these disorders is thought to be multifactorial and may differ between patients. Increase in blood ammonia levels and hyperammonemia may occur in patients receiving amino acid solutions. In some patients this may indicate hepatic insufficiency or the presence of an inborn error of amino acid metabolism [see Contraindications (4) .]Monitor liver function parameters and ammonia levels. Patients developing signs of hepatobiliary disorders should be assessed early by clinician knowledgeable in liver diseases in order to identify possible causative and contributory factors, and possible therapeutic and prophylactic interventions.. 5.8 Aluminum Toxicity. CLINIMIX contains no more than 25 mcg/L of aluminum. The aluminum contained in CLINIMIX may reach toxic levels with prolonged administration in patients with impaired kidney function. Preterm infants are at greater risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum. Patients with impaired kidney function, including preterm infants, who receive parenteral levels of aluminum at greater than to mcg/kg/day, accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.. 5.9 Risk of Parenteral Nutrition Associated Liver Disease Parenteral Nutrition Associated Liver Disease (PNULLLD) has been reported in patients who receive parenteral nutrition for extended periods of time, especially preterm infants, and can present as cholestasis or steatohepatitis. The exact etiology is unknown and is likely multifactorial. If CLINIMIX treated patients develop liver test abnormalities consider discontinuation or dosage reduction.. 5.10 Electrolyte Imbalance and Fluid Overload Patients with abnormal renal function due to pre-renal azotemia, renal obstruction, or intrinsic kidney disease may be at increased risk of electrolyte and fluid volume imbalance. Patients with cardiac insufficiency due to left ventricular systolic dysfunction are susceptible to excess fluid accumulation. Use CLINIMIX with caution in patients with cardiac insufficiency or kidney disease. CLINIMIX dosage may require adjustment with specific attention to fluid, protein, and electrolyte content in these patients.Monitor renal function parameters. Patients developing signs of kidney disease should be assessed early by clinician knowledgeable in kidney disease in order to determine the appropriate CLINIMIX dosage and other treatment options.. 5.11 Monitoring/Laboratory Tests Monitor fluid and electrolyte status, serum osmolarity, blood glucose, liver and kidney function, blood count and coagulation parameters throughout treatment. Patients receiving CLINIMIX should be monitored frequently and their electrolyte requirements individualized.