DELFLEX

1. INDICATIONS AND USAGE DELFLEX® is indicated in the treatment of chronic kidney failure in patients being maintained on peritoneal dialysis. For treatment of chronic kidney failure. ( 1 )

2. DOSAGE AND ADMINISTRATION For intraperitoneal dialysis only. ( 2 ) 2.1 Basic Dosing Information DELFLEX® is intended for intraperitoneal administration only. Not for intravenous or intra-arterial administration. The mode of therapy, frequency of treatment, formulation, exchange volume, duration of dwell, and length of dialysis should be selected by the physician responsible for the treatment of the individual patient. Utilize the peritoneal dialysis solution with lowest level of osmolarity consistent with the fluid removal requirements for that exchange. Do not store solutions containing additives. 2.2 Administration Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not heat in a microwave oven. Get Ready Clean work surface and gather supplies: Masks (enough for everyone in the room). Warmed DELFLEX peritoneal dialysis solution bag with attached stay•safe exchange set. stay•safe organizer, a stand-alone item provided separately. Povidone iodine prefilled stay•safe cap, a stand-alone item provided separately. IV Pole (optional). Prescribed medication(s), if ordered by your healthcare provider. After removing the overwrap, check your DELFLEX solution bag(s) for strength, clarity, amount, leaks, and expiration date. Do not use DELFLEX solution if leaks are found, the solution bag is damaged, the solution is cloudy or discolored, and/or the product is expired. Color may vary from clear to slightly yellow but does not affect efficacy and may be used. Prepare supplies: Retrieve stay•safe catheter extension set and ensure clamp is closed. Tear the overwrap from the slit edge down the length of the inner bag to open. Wipe away any moisture from the solution bags. Some opacity may be observed in the plastic of the bag and/ or tubing and is due to moisture absorption during the sterilization process. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Visually check that the solution bag tubing is free from kinks. If kinks are present, straighten tubing to allow the solution to flow freely. Note: Retain DELFLEX peritoneal dialysis bag sample for manufacturer evaluation and notify your healthcare provider if any of the above defects are found. Put on mask. Wash your hands per facility protocol. Position the stay•safe organizer at the edge of your clean work surface or with the stay•safe holder on the IV pole. Remove color-coded cover: Turn the blue dial as directed by the arrow in the color—coded cover. Remove the colored—coded cover from the stay•safe DISC. The blue dial will be in Position 1 ( ) DRAIN. Prepare organizer and solution bag: Place the stay•safe DISC and tubing into the organizer and tubing channels on the organizer. If you will be adding medication(s): Clean hands (as per facility's protocol). Clean the medication port as instructed by your healthcare provider. Add the medicine(s). Turn the bag upside down several times to mix the medicine(s). Hang the DELFLEX peritoneal dialysis solution bag on the IV pole and place the drain bag with the clear side up on the floor. Break cone of the administration port. Remove new stay•safe cap from its package and place stay•safe cap into the left notch of the organizer. Place stay•safe catheter extension set into organizer. Clean hands (as per facility's protocol). Place stay•safe catheter extension set into the right notch of the organizer. Ensure clamp of stay•safe catheter extension set is closed. Remove protective cap from stay•safe DISC and set aside. Connect stay•safe catheter extension set to the stay•safe DISC. Unscrew stay•safe catheter extension set from its cap. Immediately connect the stay•safe catheter extension set to the stay•safe DISC. Open the white clamp of stay•safe catheter extension set and start DRAIN. Place discarded protective cap from stay•safe DISC onto the used stay•safe cap in the …

3. DOSAGE FORMS AND STRENGTHS DELFLEX peritoneal dialysis solutions are available in transparent single-dose flexible bags comprised of either polyvinyl chloride (PVC), or a proprietary blend of polyolefins called Biofine®. The solution is clear with color being slightly yellow to colorless. All DELFLEX peritoneal dialysis solutions have overfills declared on the bag label. DELFLEX peritoneal dialysis solutions are available in the sizes and formulations shown in Table 1 . Table 1. DELFLEX peritoneal dialysis solution sizes and formulations PVC Biofine ® 3L 5L 3L 5L 6L DELFLEX Standard with 1.5% Dextrose X X X DELFLEX Standard with 2.5% Dextrose X X X DELFLEX Low Magnesium, Low Calcium with 1.5% Dextrose X X X X X DELFLEX Low Magnesium, Low Calcium with 2.5% Dextrose X X X X X DELFLEX Low Magnesium, Low Calcium with 4.25% Dextrose X X X X X DELFLEX solutions are available in multiple compositions, calculated osmolarity, pH, and ionic concentrations. See full prescribing information for detailed descriptions of each formulation. ( 3 , 11 )

4. Contraindications None. None

6. ADVERSE REACTIONS Solution related adverse reactions may include peritonitis, catheter site infection, electrolyte and fluid imbalances, hypovolemia, hypervolemia, hypertension, hypotension, disequilibrium syndrome, muscle cramping, abdominal pain, abdominal distension, and abdominal discomfort. Adverse reactions may include peritonitis, catheter site infection, electrolyte and fluid imbalances, hypovolemia, hypervolemia, hypertension, disequilibrium syndrome, muscle cramping, abdominal pain, abdominal distension, and abdominal discomfort. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Medical Care North America at 1-800-323-5188 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary DELFLEX solutions consist of electrolytes, lactate, and bicarbonate at physiological levels, and glucose to facilitate ultrafiltration. While there are no adequate and well controlled studies in pregnant women, appropriate administration of DELFLEX 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 DELFLEX. 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. 8.2 Lactation Risk Summary The components of DELFLEX solutions are excreted in human milk. Appropriate administration of DELFEX 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 in pediatric patients have not been established.

12.1 Mechanism of Action DELFLEX peritoneal dialysis solutions are hypertonic peritoneal dialysis solutions containing dextrose, a monosaccharide, as the primary osmotic agent. An osmotic gradient must be created between the peritoneal membrane and the dialysis solution in order for ultrafiltration to occur. The hypertonic concentration of glucose in DELFLEX solutions exert an osmotic pressure across the peritoneal membrane resulting in transcapillary ultrafiltration. Like other peritoneal dialysis solutions, DELFLEX solutions contain electrolytes to facilitate the correction of acid-base and electrolyte abnormalities. DELFLEX solutions contain a buffer, lactate, to help normalize acid-base abnormalities.

11. DESCRIPTION The DELFLEX® peritoneal dialysis solutions (standard and low magnesium/low calcium) are sterile, non-pyrogenic formulations of dextrose and electrolytes in water for injection, USP, for use in peritoneal dialysis. These solutions do not contain antimicrobial agents or additional buffers. Composition, calculated osmolarity, pH, and ionic concentrations are shown in Table 2 . Table 2. Composition, calculated osmolarity, pH and ionic concentration Composition/100mL Total Osmolarity (mOsmoL/L) (calc) pH (5.0 - 6.0) Ionic Concentration (mEq/L) Dextrose Hydrous, USP (C 6 H 12 O 6 ⋅H 2 O) Sodium Chloride. USP (NaCI) Sodium Lactate (C 3 H 5 NaO 3 ) Calcium Chloride, USP (CaCl 2 ⋅2H 2 O) Magnesium Chloride, USP (MgCl 2 -6H 2 0) Sodium Calcium Magnesium Chloride Lactate DELFLEX Standard with 1.5% Dextrose 1,500 mg 567 mg 392 mg 25.7 mg 15.2 mg 347 5.5 132 3.5 1.5 102 35 DELFLEX Standard with 2.5% Dextrose 2,500 mg 567 mg 392 mg 25.7 mg 15.2 mg 398 5.5 132 3.5 1.5 102 35 DELFLEX Low Magnesium, Low Calcium with 1.5% Dextrose 1,500 mg 538 mg 448 mg 18.4 mg 5.08 mg 344 5.5 132 2.5 0.5 95 40 DELFLEX Low Magnesium, Low Calcium with 2.5% Dextrose 2,500 mg 538 mg 448 mg 18.4 mg 5.08 mg 394 5.5 132 2.5 0.5 95 40 DELFLEX Low Magnesium, Low Calcium with 4.25% Dextrose 4,250 mg 538 mg 448 mg 18.4 mg 5.08 mg 483 5.5 132 2.5 0.5 95 40 Dextrose, USP, is chemically designated D-glucose monohydrate (C 6 H 12 O 6 •H 2 O) a hexose sugar freely soluble in water. The structural formula is shown here: Calcium chloride, USP, is chemically designated calcium chloride dihydrate (CaCl 2 •2H 2 O) white fragments or granules freely soluble in water. Magnesium chloride, USP, is chemically designated magnesium chloride hexahydrate (MgCl 2 •6H 2 O) colorless flakes or crystals very soluble in water. Sodium lactate solution, USP, is chemically designated (CH 3 CH(OH)COONa), a 60% aqueous solution miscible in water. Sodium chloride, USP, is chemically designated (NaCl), a white, crystalline compound freely soluble in water. Water for injection, USP, is chemically designated (H 2 O). Hydrochloric Acid or Sodium Hydroxide may be added for pH adjustment. pH is 5.5 ± 0.5. Exposure to temperatures above 25°C (77°F) during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period. Since the inner bag is compounded from flexible plastic, water may permeate from the inner bag into the overwrap in quantities insufficient to affect the solution significantly. Solutions in contact with the plastic inner bag can cause certain chemical components of the bag to leach out in very small amounts; however, the safety of the plastic formulation is supported by biological tests for plastic containers. Structural Formula

16. HOW SUPPLIED/STORAGE AND HANDLING DELFLEX peritoneal dialysis solutions are available in the sizes and formulations shown in Table 1 [see Dosage Forms and Strengths ( 3 )] . DELFLEX peritoneal dialysis solutions are delivered in transparent, single-dose flexible bags. The solution is clear with color being slightly yellow to colorless. Table 3. DELFLEX peritoneal dialysis NDC designations PVC Biofine ® Unit Volume 3L 5L 3L 5L 6L Number of units per carton 4 2 4 2 2 Standard 1.5% Dextrose 49230- 188-50 49230- 188-52 49230- 188-62 Standard 2.5% Dextrose 49230- 191-50 49230- 191-52 49230- 191-62 Low Mg/Low Ca 1.5% Dextrose 49230- 206-30 49230- 206-50 49230- 206-32 49230- 206-52 49230- 206-62 Low Mg/Low Ca 2.5% Dextrose 49230- 209-30 49230- 209-50 49230- 209-32 49230- 209-52 49230- 209-62 Low Mg/Low Ca 4.25% Dextrose 49230- 212-30 49230- 212-50 49230- 212-32 49230- 212-52 49230- 212-62 Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). See USP Controlled Room Temperature. Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized. Keep DELFLEX and all medicines out of the reach of children.