PRISMASOL B22GK4/0

6 ADVERSE REACTIONS The following adverse reactions have been identified during post approval use with these or other similar products and therefore may occur with use of PHOXILLUM or PRISMASOL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Metabolic acidosis • Hypotension • Acid-base disorders • Electrolyte imbalance including calcium ionized increased (reported in PRISMASOL solutions containing calcium), hyperphosphatemia, and hypophosphatemia • Fluid imbalance

4 CONTRAINDICATIONS PHOXILLUM and PRISMASOL replacement solutions are contraindicated in patients with known hypersensitivities to these products. Known hypersensitivities to PRISMASOL and PHOXILLUM solutions ( 4 )

11 DESCRIPTION PRISMASOL and PHOXILLUM solutions are clear, sterile, free of bacterial endotoxins and contain no bacteriostatic or antimicrobial agents. These solutions are used in Continuous Renal Replacement Therapies (CRRT) as a replacement solution in hemofiltration and hemodiafiltration. Depending on the product (see Table 2 ), the two compartments contain: Calcium chloride, USP, is chemically designated calcium chloride dihydrate (CaCl 2 • 2H 2 O). Magnesium chloride, USP, is chemically designated magnesium chloride hexahydrate (MgCl 2 • 6H 2 O). Sodium chloride, USP, is chemically designated NaCl. Potassium chloride, USP, is chemically designated KCl. Sodium bicarbonate, USP, is chemically designated NaHCO 3 . Dextrose, USP, is chemically designated D-Glucose anhydrous (C 6 H 12 O 6 ) or D-Glucose monohydrate (C 6 H 12 O 6 • H 2 O). Lactic acid, USP, is chemically designated CH 3 CH(OH)COOH. Dibasic sodium phosphate, USP, is chemically designated as disodium hydrogen phosphate, dihydrate (Na 2 HPO 4 • 2H 2 O) Table 2 - Compartment Composition (Before Mixing) Compartment A (g/L) Compartment B (g/L) Calcium Chloride ∙ 2H 2 O Magnesium Chloride ∙ 6H 2 O Dextrose anhydrous (as monohydrate) Lactic Acid Sodium Chloride Sodium bicarbonate Potassium Chloride Sodium Phosphate ∙ 2H 2 O PRISMASOL SOLUTIONS BGK 0/2.5 3.68 3.05 20 (22) 5.40 6.46 3.09 0 0 BGK 4/2.5 3.68 3.05 20 (22) 5.40 6.46 3.09 0.314 0 BGK 2/3.5 5.15 2.03 20 (22) 5.40 6.46 3.09 0.157 0 BGK 2/0 0 2.03 20 (22) 5.40 6.46 3.09 0.157 0 B22GK 4/0 0 3.05 20 (22) 5.40 7.07 2.21 0.314 0 BK 0/0/1.2 0 2.44 0 (0) 5.40 6.46 3.09 0 0 BGK 4/0/1.2 0 2.44 20 (22) 5.40 6.46 3.09 0.314 0 PHOXILLUM SOLUTIONS BK 4/2.5 3.68 3.05 0 (0) 0 6.34 3.09 0.314 0.187 B22K 4/0 0 3.05 0 (0) 0 6.95 2.21 0.314 0.187 The pH of the final solution is in the range of 7.0 to 8.5.

2 DOSAGE AND ADMINISTRATION • Therapy must be individualized based on the patient's clinical condition, fluid, electrolyte, acid-base and glucose balance ( 2.2 ) • Solution must be mixed prior to use ( 2.2 ) • Use only with extracorporeal dialysis equipment appropriate for CRRT ( 2.3 ) 2.1 Administration Instructions Visually inspect PRISMASOL and PHOXILLUM for particulate matter and discoloration prior to administration. Administration should only be under the direction of a physician competent in intensive care treatment including CRRT. Use only with extracorporeal dialysis equipment appropriate for CRRT. The prepared solution is for single patient use only. Aseptic technique should be used throughout administration to the patient. Discard any unused solution. 2.2 Dosing Considerations PRISMASOL replacement solutions contain 4 different combinations of active ingredients (7 different products with varying ingredient amounts). PHOXILLUM replacement solutions contain 2 different combinations of active ingredients (2 different products with varying ingredient amounts). PRISMASOL and PHOXILLUM are supplied in a two-compartment bag that must be mixed immediately prior to use [see Dosage and Administration (2.3) ]: • Small compartment A (250 mL) containing an electrolyte solution, and • Large compartment B (4750 mL) containing the buffer solution. See Table 1 for the concentrations of the active ingredients (after mixing) in these 9 different replacement solutions (total volume is 5 Liters). Table 1: Concentrations of Active Ingredients in the 7 PRISMASOL and 2 PHOXILLUM Replacement Solutions after Mixing Ca 2+ mEq/L HCO 3 - mEq/L K + mEq/L Mg 2+ mEq/L Na + mEq/L HPO 4 2- mmol/L Cl - mEq/L Lactate mEq/L Dextrose mg/dL Osmolarity mOsm/L Ca 2+ = calcium, HCO 3 - = bicarbonate, K + = potassium, Mg 2+ = magnesium, Na + = sodium, HPO 4 2- = phosphate, Cl- = chloride; osmolarity is estimated PRISMASOL Replacement Solutions BGK0/2.5 2.5 32 0 1.5 140 0 109 3 100 292 BGK4/2.5 2.5 32 4 1.5 140 0 113 3 100 300 BGK2/3.5 3.5 32 2 1 140 0 111.5 3 100 296 BGK2/0 0 32 2 1 140 0 108 3 100 291 B22GK4/0 0 22 4 1.5 140 0 120.5 3 100 296 BGK4/0/1.2 0 32 4 1.2 140 0 110.2 3 100 295 BK0/0/1.2 0 32 0 1.2 140 0 106.2 3 0 282 PHOXILLUM Replacement Solutions BK4/2.5 2.5 32 4 1.5 140 1 114.5 0 0 294 B22K4/0 0 22 4 1.5 140 1 122 0 0 290 The mode of therapy, solute formulation, flow rates, and length of PRISMASOL and PHOXILLUM replacement therapy in CRRT should be established by a physician based on the patient’s clinical condition, blood concentration of phosphate and other electrolytes, acid-base and glucose balance. Administer either PRISMASOL or PHOXILLUM into the extracorporeal circuit: • Before (pre-dilution) the hemofilter or hemodiafilter, • After (post-dilution) the hemofilter or hemodiafilter, or • Before and after the hemofilter or hemodiafilter. 2.3 Preparing the Solution Use only if the overwrap is not damaged, all seals are intact, peel seal is not broken, and the solution is clear. The solution may be warmed to 37°C/98.6°F prior to removing the overwrap to enhance patient comfort. However, only dry heat should be used. Solutions should not be heated in water or in a microwave oven. After heating, verify that the solution remains clear and contains no particulate matter. The solutions are supplied in two different two-compartment bags made of polyolefin with a peel seal separating compartment A and B (see Figure 1 ). Follow the instructions below when connecting the solution bags for correct use of the access ports. Instructions for preparing solutions supplied in a two-compartment, polyolefin bag with a peel seal: Figure 1 Figure 1 Figure 2 Step 1 Immediately before use, remove the overwrap from the bag and mix the solutions in the two different compartments. After removing the overwrap, inspect the bag for leakage by pressing firmly on the bag. Discard the bag if any leakage is detected since sterility cannot be assured. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the mixed solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Hold the small compartment with both hands and squeeze it until an opening is created in the peel seal. (See Figure 2 beside) Figure 3 Step 2 Squeeze with both hands on the large compartment until the peel seal between the two compartments is entirely open. Shake gently to mix. (See Figure 3 beside) The solution is now ready to use and the bag can be hung on the equipment. Figure 4a Step 3 The replacement line may be connected to the bag through either of the luer connector or the injection connector (spike connector). Step 3a The luer connector is a needle-less and swabbable connector. Remove the cap with a twist and pull motion, and connect the male luer lock on the replacement line to the female luer receptor on the bag. (See Figure 4 a beside) Ensure that the connection is fully seated and tighten. The connector is now open. Verify that the fluid is flowing freely during use. When the replacement line is disconnected from the luer connector, the connector will close and the flow of the solution will stop. Figure 4b Step 3b If the injection connector (spike connector) is used, first remove the snap-off cap. Then introduce the replacement line spike through the rubber septum of the bag connector. (See Figure 4 b beside) Ensure that the spike is fully inserted and verify that the fluid is flowing freely during use. Figure 2 Figure 3 Figure 4a Figure 4b 2.4 Adding Drugs to the Solutions After mixing, additional drugs may be added to the bag via injection connector (spike connector) in large compartment B. In general, administer drugs other than phosphate through a different access line. When introducing drugs, use aseptic techniques and mix thoroughly prior to connecting the solution bag to the extracorporeal circuit. Do not use if there is a color change and/or the appearance of precipitates, insoluble complexes or crystals after addition of medication. Phosphate: Up to 1.2 mmol/L of phosphate can be added to the bag as potassium phosphate or sodium phosphate. The total potassium concentration of PRISMASOL solution should not exceed 4 mEq/L. Use sodium phosphate to add phosphate if the total potassium concentration in PRISMASOL solution is 4 mEq/L. PHOXILLUM Solutions: Phosphate: Phosphate up to 0.2 mmol/L may be added to the solution. Use sodium phosphate if adding phosphate to bag. The total phosphate concentration should not exceed 1.2 mmol/L.

1 INDICATIONS AND USAGE PRISMASOL and PHOXILLUM solutions are indicated in pediatric and adult patients for use as a replacement solution in Continuous Renal Replacement Therapy (CRRT) to replace plasma volume removed by ultrafiltration and to correct electrolyte and acid-base imbalances. They may also be used in case of drug poisoning when CRRT is used to remove dialyzable substances. PRISMASOL and PHOXILLUM solutions are indicated: • As a replacement solution in Continuous Renal Replacement Therapy (CRRT) and in case of drug poisoning when CRRT is used to remove dialyzable substances ( 1 )

7 DRUG INTERACTIONS As with the use of other replacement solutions, blood concentrations of dialyzable drugs may be reduced by CRRT due to their removal by the hemofilter or hemodiafilter. The blood concentrations of certain drugs may need to be monitored and appropriate therapy implemented to correct for removal during treatment. 7.1 Citrate When used as an anticoagulant, citrate contributes to the overall buffer load and can reduce plasma calcium levels. Select the PRISMASOL/PHOXILLUM formulation(s) accordingly.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action PRISMASOL and PHOXILLUM solutions are pharmacologically inactive. The electrolyte concentrations in the solutions are chosen to restore plasma levels to clinically desired concentrations or maintain plasma levels at the desired concentrations. PRISMASOL and PHOXILLUM solutions are used as replacement solution to replace water and electrolytes removed during hemofiltration and hemodiafiltration. Bicarbonate (or precursor lactate) in the solution is used as an alkalinizing buffer to restore acid-base balance to a clinically desirable level. 12.3 Pharmacokinetics The distribution of electrolytes, bicarbonate, and dextrose is determined by the patient's clinical condition, metabolic status, and residual renal function. The elimination and replacement of water, electrolytes and buffer depend on the patient's electrolyte and acid-base balance, metabolic status, residual renal function and ongoing physiologic losses through intestinal, respiratory and cutaneous routes.

12.1 Mechanism of Action PRISMASOL and PHOXILLUM solutions are pharmacologically inactive. The electrolyte concentrations in the solutions are chosen to restore plasma levels to clinically desired concentrations or maintain plasma levels at the desired concentrations. PRISMASOL and PHOXILLUM solutions are used as replacement solution to replace water and electrolytes removed during hemofiltration and hemodiafiltration. Bicarbonate (or precursor lactate) in the solution is used as an alkalinizing buffer to restore acid-base balance to a clinically desirable level.

12.3 Pharmacokinetics The distribution of electrolytes, bicarbonate, and dextrose is determined by the patient's clinical condition, metabolic status, and residual renal function. The elimination and replacement of water, electrolytes and buffer depend on the patient's electrolyte and acid-base balance, metabolic status, residual renal function and ongoing physiologic losses through intestinal, respiratory and cutaneous routes.

20181101

27

3 DOSAGE FORMS AND STRENGTHS See Table 1 for the concentrations of the active ingredients (after mixing) in these 9 different replacement solutions [see Dosage and Administration (2.2) ] . PRISMASOL and PHOXILLUM are available in multiple combinations of ingredients and in multiple variations of strengths. See full Prescribing Information for detailed descriptions of each formulation. ( 2 , 3 , 11 )

PRISMASOL BGK0/2.5 calcium chloride, magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride and sodium bicarbonate CALCIUM CHLORIDE CALCIUM CATION CHLORIDE ION MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION WATER CARBON DIOXIDE PRISMASOL BGK4/2.5 calcium chloride, magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride CALCIUM CHLORIDE CALCIUM CATION CHLORIDE ION MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION WATER CARBON DIOXIDE PRISMASOL BGK2/3.5 calcium chloride, magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride CALCIUM CHLORIDE CALCIUM CATION CHLORIDE ION MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION WATER CARBON DIOXIDE PRISMASOL BGK2/0 magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION WATER CARBON DIOXIDE PRISMASOL B22GK4/0 magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION WATER CARBON DIOXIDE PRISMASOL BK0/0/1.2 magnesium chloride, lactic acid, sodium chloride and sodium bicarbonate MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION WATER CARBON DIOXIDE PRISMASOL BGK4/0/1.2 magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION DEXTROSE MONOHYDRATE ANHYDROUS DEXTROSE LACTIC ACID, UNSPECIFIED FORM LACTIC ACID, UNSPECIFIED FORM SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION WATER CARBON DIOXIDE PHOXILLUM BK4/2.5 calcium chloride, magnesium chloride, sodium chloride, sodium bicarbonate, potassium chloride and sodium phosphate dibasic dihydrate CALCIUM CHLORIDE CALCIUM CATION CHLORIDE ION MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION SODIUM PHOSPHATE, DIBASIC, DIHYDRATE SODIUM CATION PHOSPHATE ION WATER CARBON DIOXIDE HYDROCHLORIC ACID PHOXILLUM B22K4/0 magnesium chloride, sodium chloride, sodium bicarbonate, potassium chloride and sodium phosphate dibasic dihydrate MAGNESIUM CHLORIDE MAGNESIUM CATION CHLORIDE ION SODIUM CHLORIDE SODIUM CATION CHLORIDE ION SODIUM BICARBONATE SODIUM CATION BICARBONATE ION POTASSIUM CHLORIDE POTASSIUM CATION CHLORIDE ION SODIUM PHOSPHATE, DIBASIC, DIHYDRATE SODIUM CATION PHOSPHATE ION WATER CARBON DIOXIDE HYDROCHLORIC ACID

NDA021703

PRISMASOL B22GK4/0

magnesium chloride, dextrose monohydrate, lactic acid, sodium chloride, sodium bicarbonate and potassium chloride

24571-111

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

Package/Label Display Panel Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-108-06 OK + mEq/L 2.5 Ca 2+ mEq/L PrismaSolBGK0/2.5 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Calcium chloride • 2H 2 O 3.68 Magnesium chloride • 6H 2 O 3.05 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 6.46 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 1.25 0.75 140 109.0 3.0 32 0 5.5 mEq/L 2.5 1.5 140 109.0 3.0 32 0 (100 mg/dL) Theoretical osmolarity: 292 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091613 Product # 110240 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0110 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-105-06 4K + mEq/L 2.5 Ca 2+ mEq/L PrismaSolBGK4/2.5 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Calcium chloride • 2H 2 O 3.68 Magnesium chloride • 6H 2 O 3.05 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 6.46 Potassium chloride 0.314 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 1.25 0.75 140 113.0 3.0 32 4.0 5.5 mEq/L 2.5 1.5 140 113.0 3.0 32 4.0 (100 mg/dL) Theoretical osmolarity: 300 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091637 Product # 110242 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0112 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-103-06 2K + mEq/L 3.5 Ca 2+ mEq/L PrismaSolBGK2/3.5 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Calcium chloride • 2H 2 O 5.15 Magnesium chloride • 6H 2 O 2.03 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 6.46 Potassium chloride 0.157 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment Rx only A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 1.75 0.5 140 111.5 3.0 32 2.0 5.5 mEq/L 3.5 1.0 140 111.5 3.0 32 2.0 (100 mg/dL) Theoretical osmolarity: 296 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091644 Product # 110243 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0113 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-102-06 2K + mEq/L 0Ca 2+ mEq/L PrismaSol BGK2/0 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Magnesium chloride • 6H 2 O 2.03 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 6.46 Potassium chloride 0.157 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 0 0.5 140 108.0 3.0 32 2.0 5.5 mEq/L 0 1.0 140 108.0 3.0 32 2.0 (100 mg/dL) Theoretical osmolarity: 291 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091651 Product # 110244 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0114 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-111-06 4K + mEq/L Bicarbonate 22 0Ca 2+ mEq/L PrismaSol B22GK4/0 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Magnesium chloride • 6H 2 O 3.05 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 7.07 Potassium chloride 0.314 Lactic acid 5.40 Sodium bicarbonate 2.21 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 0 0.75 140 120.5 3.0 22 4.0 5.5 mEq/L 0 1.5 140 120.5 3.0 22 4.0 (100 mg/dL) Theoretical osmolarity: 296 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414116781 Product # 115001 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0115 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-113-06 0K + mEq/L 0Ca 2+ mEq/L PrismaSol BK0/0/1.2 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Magnesium chloride • 6H 2 O 2.44 Sodium chloride 6.46 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 0 0.6 140 106.2 3.0 32 0 0 mEq/L 0 1.2 140 106.2 3.0 32 0 (0 mg/dL) Theoretical osmolarity: 282 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091309 Product # 110239 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0109 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Barcode NDC# 24571-114-06 4K + mEq/L 0Ca 2+ mEq/L PrismaSol BGK4/0/1.2 Rx only Barcode Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution each 1000 mL contains (g) A B Magnesium chloride • 6H 2 O 2.44 Dextrose anhydrous 20.0 (as dextrose monohydrate) 22.0 Sodium chloride 6.46 Potassium chloride 0.314 Lactic acid 5.40 Sodium bicarbonate 3.09 Water for injections q.s, Carbon dioxide for pH adjustment A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Lactate C 3 H 5 O 3 - Bicarbonate HCO 3 - Potassium K + Dextrose mmol/L 0 0.6 140 110.2 3.0 32 4.0 5.5 mEq/L 0 1.2 140 110.2 3.0 32 4.0 (100 mg/dL) Theoretical osmolarity: 295 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UNUSED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled room Temperature.] Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. 5000 mL EAN-14: 07332414091620 Product # 110241 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0111 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Compartment B Barcode NDC# 24571-116-06 4K + mEq/L 1 Phosphate mmol/L 2.5 Ca 2+ mEq/L Phoxillum BK4/2.5 Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution, each 1000 mL contains (g): A B Calcium chloride • 2H 2 O 3.68 Magnesium chloride • 6H 2 O 3.05 Sodium chloride 6.34 Potassium chloride 0.314 Sodium bicarbonate 3.09 Dibasic sodium phosphate • 2H 2 O 0.187 Water for injections q.s Rx only A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Bicarbonate HCO 3 - Potassium K + Phosphate HPO 4 2- Dextrose mmol/L 1.25 0.75 140 114.5 32 4.0 1 0 mEq/L 2.5 1.5 140 114.5 32 4.0 (1 mmol/L) (0 mg/dL) Theoretical osmolarity: 294 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UN- USED SOLUTION. Store at +20ºC to +25ºC (+68ºF to +77ºF); excursions permitted to +15ºC - +30ºC (+59ºF to +86ºF). [See USP Controlled Room Temperature]. Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. Carbon dioxide and diluted hydrochloric acid added for pH adjustment. 5000 mL EAN-14: 07332414116040 Product # 114905 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0107 Mixing steps ① SQUEEZE TOP corners to break seal ② Squeeze BAG SIDES to fully open seal Compartment B Barcode NDC# 24571-117-06 4K + mEq/L 0 Ca 2+ mEq/L 22 Bicarbonate mEq/L 1 Phosphate mmol/L Phoxillum B22K4/0 Replacement Solution for Continuous Renal Replacement Therapy Before reconstitution, each 1000 mL contains (g): A B Magnesium chloride • 6H 2 O 3.05 Sodium chloride 6.95 Potassium chloride 0.314 Sodium bicarbonate 2.21 Dibasic sodium phosphate • 2H 2 O 0.187 Water for injections q.s Rx only A 250 mL B 4750 mL After reconstitution, A + B Calcium Ca 2+ Magnesium Mg 2+ Sodium Na + Chloride Cl - Bicarbonate HCO 3 - Potassium K + Phosphate HPO 4 2- Dextrose mmol/L 0 0.75 140 122.0 22 4.0 1 0 mEq/L 0 1.5 140 122.0 22 4.0 (1 mmol/L) (0 mg/dL) Theoretical osmolarity: 290 mOsm/L pH: 7.0 – 8.5 Mix both compartments before use. See package insert for dosage information and further instructions. Sterile and free from bacterial endotoxins. Confirm the integrity of the packaging. Use only if solution is clear. For single use only. DISCARD ANY UN- USED SOLUTION. Store at +20°C to +25°C (+68°F to +77°F); excursions permitted to +15°C to +30°C (+59°F to +86°F). [See USP Controlled Room Temperature]. Do not freeze or expose to excessive heat. As soon as the overwrap is removed, the reconstitution of compartments A and B should be done and the reconstituted solution should be used immediately. After removal of the overwrap, the solution is stable for 24 hours including the duration of the treatment. Mix additives BEFORE connecting this bag to the extracorporeal circuit. (See insert for further information.) This product is not made with natural rubber latex. Carbon dioxide and diluted hydrochloric acid added for pH adjustment. 5000 mL EAN-14: 07332414116057 Product # 114906 Batch No. and expiry date are printed on the back of the bag. Manufactured for: Baxter Healthcare Corporation Deerfield IL 60015 USA Made in Italy GAMBRO Logo REPLACEMENT Solution for Continuous Renal Replacement Therapy 07-25-00-0108 PrismaSol Representative Container Label BGK0/2.5 PrismaSol Representative Container Label BGK4/2.5 PrismaSol Representative Container Label BGK2/3.5 PrismaSol Representative Container Label BGK2/0 PrismaSol Representative Container Label B22GK4/0 PrismaSol Representative Container Label BK0/0/1.2 PrismaSol Representative Container Label BGK4/0/1.2 Phoxillum Representative Container Label BK4/2.5 Phoxillum Representative Container Label B22K4/0

8.5 Geriatric Use The experience with PRISMASOL and PHOXILLUM solutions in geriatric patients has not identified novel concerns.

8.4 Pediatric Use Safety and effectiveness have been established based on published clinical data of CRRT replacement solutions with compositions similar to PRISMASOL and PHOXILLUM used in adults and two hemofiltration studies in pediatric patients, including a study of newborns to 17 years old.

8.1 Pregnancy Risk Summary PRISMASOL and PHOXILLUM are pharmacologically inactive solutions. While there are no adequate and well controlled studies in pregnant women, appropriate administration of PRISMASOL and PHOXILLUM solutions with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to cause fetal harm. Animal reproduction studies have not been conducted with PRISMASOL and PHOXILLUM solutions. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Maintenance of normal acid-base balance is important for fetal well-being.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary PRISMASOL and PHOXILLUM are pharmacologically inactive solutions. While there are no adequate and well controlled studies in pregnant women, appropriate administration of PRISMASOL and PHOXILLUM solutions with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to cause fetal harm. Animal reproduction studies have not been conducted with PRISMASOL and PHOXILLUM solutions. The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Maintenance of normal acid-base balance is important for fetal well-being. 8.2 Lactation Risk Summary The components of PRISMASOL and PHOXILLUM solutions are excreted in human milk. Appropriate administration of PRISMASOL and PHOXILLUM solutions with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to harm a nursing infant. 8.4 Pediatric Use Safety and effectiveness have been established based on published clinical data of CRRT replacement solutions with compositions similar to PRISMASOL and PHOXILLUM used in adults and two hemofiltration studies in pediatric patients, including a study of newborns to 17 years old. 8.5 Geriatric Use The experience with PRISMASOL and PHOXILLUM solutions in geriatric patients has not identified novel concerns.

16 HOW SUPPLIED/STORAGE AND HANDLING PRISMASOL and PHOXILLUM solutions are supplied in a two-compartment bag made of polyolefin. The 5000 mL bag is composed of a small compartment (250 mL) and a large compartment (4750 mL). The two compartments are separated by a peel seal. The bag is overwrapped with a transparent overwrap. See Table 2 for the concentrations of the active ingredients in each compartment for each product [see Description (11) ]. Container Fill Volume NDC PRISMASOL Solutions PRISMASOL BGK0/2.5 5000 mL 24571-108-06 PRISMASOL BGK4/2.5 5000 mL 24571-105-06 PRISMASOL BGK2/3.5 5000 mL 24571-103-06 PRISMASOL BGK2/0 5000 mL 24571-102-06 PRISMASOL B22GK4/0 5000 mL 24571-111-06 PRISMASOL BK0/0/1.2 5000 mL 24571-113-06 PRISMASOL BGK4/0/1.2 5000 mL 24571-114-06 PHOXILLUM Solutions PHOXILLUM BK4/2.5 5000 mL 24571-116-06 PHOXILLUM B22K4/0 5000 mL 24571-117-06 Not all formulations may be marketed. Storage conditions Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). [See USP Controlled Room Temperature] Do not freeze or expose to excessive heat. Do not use if precipitate has formed or if container seals have been damaged. Manufactured for: Baxter Healthcare Corporation One Baxter Parkway Deerfield, Illinois 60015 07-19-00-0408 Baxter, Gambro, Phoxillum and PrismaSol are trademarks of Baxter International Inc., or its subsidiaries

Storage conditions Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15ºC to 30ºC (59ºF to 86ºF). [See USP Controlled Room Temperature] Do not freeze or expose to excessive heat. Do not use if precipitate has formed or if container seals have been damaged. Manufactured for: Baxter Healthcare Corporation One Baxter Parkway Deerfield, Illinois 60015 07-19-00-0408 Baxter, Gambro, Phoxillum and PrismaSol are trademarks of Baxter International Inc., or its subsidiaries