DIANEAL LOW CALCIUM WITH DEXTROSE

1 INDICATIONS AND USAGE DIANEAL peritoneal dialysis solutions are indicated for patients in acute or chronic renal failure. For management of acute or chronic renal failure.

2 DOSAGE AND ADMINISTRATION For intraperitoneal administration only. ( 2 ) 2.1 Basic Dosing Information DIANEAL peritoneal dialysis solutions are intended for intraperitoneal administration only. Not for intravenous or intra-arterial administration. Select mode of therapy, frequency of treatment, formulation, fill volume, duration of dwell, and length of dialysis based on the patient’s clinical condition, fluid, electrolyte and specific needs. The fill volume depends on body size, usually from 2.0 to 2.5 liters per 1.73m 2 for adults. DIANEAL peritoneal dialysis solutions are intended for use in Continuous Ambulatory Peritoneal Dialysis (CAPD) or Automated Peritoneal Dialysis (APD). Refer to directions accompanying ancillary equipment for CAPD and APD system preparation. Product Selection To avoid the risk of severe dehydration and hypovolemia and to minimize the loss of protein, it is advisable to select the peritoneal dialysis solution with the lowest level of osmolarity consistent with the fluid removal requirements for that exchange. As the patient’s body weight becomes closer to the ideal dry weight, lowering the dextrose concentration of DIANEAL solution is recommended. DIANEAL 4.25% dextrose-containing solution has the highest osmolarity of the DIANEAL solutions and using it for all exchanges may cause dehydration [see Dosage Forms and Strengths (3) ] . 2.2 Adding Medications If the resealable rubber plug on the medication port is missing or partly removed, do not use the product if medication is to be added. To add a medication: 1. Put on mask. Clean and/or disinfect hands. 2. Prepare medication port site using aseptic technique. 3. Using a syringe with a 1-inch long, 25- to 19-gauge needle, puncture the medication port and inject additive. 4. Reposition container with container ports up and evacuate medication port by squeezing and tapping it. 5. Mix solution and additive thoroughly. 2.3 Directions for Use Warming DIANEAL peritoneal dialysis solution can be warmed to 37°C (98.6°F). Only dry heat should be used. For CAPD, it is best to warm solutions within the overwrap using a heating pad. Do not immerse DIANEAL solutions in water for warming. Do not use a microwave oven to warm DIANEAL solutions. To Open To open, tear the overwrap down at the slit and remove the solution container. Do not use sharp objects to remove the overwrap. Product Inspection Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use solutions that are cloudy, discolored, contain visible particulate matter, or show evidence of leakage. Some opacity of the plastic, due to moisture absorption during the sterilization process, may be observed. This does not affect the solution quality or safety and may often leave a slight amount of moisture within the overwrap. The opacity should diminish gradually. Inspect the bag connector to ensure the tip protector (pull ring or blue pull tip) is attached. Do not use if the tip protector is not attached to the connector. Inspect the DIANEAL solution container for signs of leakage and check for minute leaks by squeezing the container firmly. If the container has frangible(s), inspect that they are positioned correctly and are not broken. Do not use DIANEAL solution if the frangible(s) are broken or leaks are suspected as sterility may be impaired. For DIANEAL solutions in ULTRABAG containers, inspect the tubing and drain container for presence of solution. Small droplets are acceptable, but if solution flows past the frangible prior to use, do not use and discard the units. CAPD therapy using ULTRABAG containers Select appropriate formulation from Table 1. Put on mask. Clean and/or disinfect hands. Using aseptic technique; 1. Uncoil tubing and drain bag, ensuring that the transfer set is closed. 2. Break the connector (Y-set) frangible. 3. Remove the tip protector from connector of solution container. Do not reuse the solution or container …

3 DOSAGE FORMS AND STRENGTHS DIANEAL peritoneal dialysis solution is clear with color being slightly yellow to colorless and is formulated with the following ionic concentrations: Table 1 - DIANEAL PD-2 and Low Calcium Peritoneal Dialysis Solution ULTRABAG Container for CAPD therapy AMBU-FLEX Container with pull ring for APD therapy Ionic Concentration (mEq/L) OSMOLARITY (mOsmol/L) (calc) pH Sodium Calcium Magnesium Chloride Lactate DIANEAL PD-2 1.5% Dextrose 346 5.2 (4.0 to 6.5) 132 3.5 0.5 96 40 DIANEAL PD-2 2.5% Dextrose 396 5.2 (4.0 to 6.5) 132 3.5 0.5 96 40 DIANEAL PD-2 4.25% Dextrose 485 5.2 (4.0 to 6.5) 132 3.5 0.5 96 40 DIANEAL Low Calcium (2.5 mEq/L) 1.5% Dextrose 344 5.2 (4.0 to 6.5) 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 2.5% Dextrose 395 5.2 (4.0 to 6.5) 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 4.25% Dextrose 483 5.2 (4.0 to 6.5) 132 2.5 0.5 95 40 Table 2 - DIANEAL Low Calcium Peritoneal Dialysis Solution Plastic container with blue pull tip for APD therapy Ionic Concentration (mEq/L) OSMOLARITY (mOsmol/L) (calc) pH Sodium Calcium Magnesium Chloride Lactate DIANEAL Low Calcium (2.5 mEq/L) 1.5% Dextrose 344 5.0 to 6.5 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 2.5% Dextrose 395 5.0 to 6.5 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 4.25% Dextrose 483 5.0 to 6.5 132 2.5 0.5 95 40 Table 3 – DIANEAL PD-2 and DIANEAL Low Calcium Peritoneal Dialysis Solution Plastic container with pull ring for APD therapy OSMOLARITY (mOsmol/L) (calc) pH Ionic Concentration (mEq/L) Sodium Calcium Magnesium Chloride Lactate DIANEAL PD-2 1.5% Dextrose 346 5.0 to 5.6 132 3.5 0.5 96 40 DIANEAL PD-2 2.5% Dextrose 396 5.0 to 5.6 132 3.5 0.5 96 40 DIANEAL PD-2 4.25% Dextrose 485 5.0 to 5.6 132 3.5 0.5 96 40 DIANEAL Low Calcium (2.5 mEq/L) 1.5% Dextrose 344 5.0 to 5.6 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 2.5% Dextrose 395 5.0 to 5.6 132 2.5 0.5 95 40 DIANEAL Low Calcium (2.5 mEq/L) 4.25% Dextrose 483 5.0 to 5.6 132 2.5 0.5 95 40 DIANEAL solutions are available in multiple combinations of ingredients and in composition, calculated osmolarity, pH, and ionic concentrations. See full prescribing information for detailed descriptions of each formulation. ( 3 )

4 CONTRAINDICATIONS DIANEAL peritoneal dialysis solutions are contraindicated in patients with severe lactic acidosis. • Pre-existing severe lactic acidosis ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the label: Peritonitis and Encapsulating Peritoneal Sclerosis [see Warnings and Precautions (5.1) ] Electrolyte and Fluid Imbalances [see Warnings and Precautions (5.4) ] To report SUSPECTED ADVERSE REACTIONS, contact Vantive US Healthcare LLC at 1-855-857-0003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience There are no data available on adverse reactions from controlled clinical trials conducted to evaluate the safety of DIANEAL peritoneal dialysis solutions. 6.2 Post-Marketing Experience The following adverse experiences have been identified during post-approval use of DIANEAL solutions or in conjunction with performing the peritoneal dialysis procedure. Because these experiences are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship during drug exposure. Most of these adverse experiences are believed to be consequences of peritoneal dialysis. INFECTIONS AND INFESTATIONS: Fungal peritonitis, Peritonitis bacterial, Catheter related infection METABOLISM AND NUTRITION DISORDERS: Hypovolemia, Hypervolemia, Fluid retention, Hypokalemia, Hyponatremia, Dehydration, Hypochloremia VASCULAR DISORDERS: Hypotension, Hypertension RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Dyspnea GASTROINTESTINAL DISORDERS: Sclerosing encapsulating peritonitis, Peritonitis, Peritoneal cloudy effluent, Vomiting, Diarrhea, Nausea, Constipation, Abdominal pain, Abdominal distension, Abdominal discomfort SKIN AND SUBCUTANEOUS DISORDERS: Stevens-Johnson syndrome, Urticaria, Rash, (including pruritic, erythematous and generalized), Pruritus MUSCULOSKELETAL, CONNECTIVE TISSUE DISORDERS: Myalgia, Muscle spasms, Musculoskeletal pain GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Generalized edema, Pyrexia, Malaise, Infusion site pain, Catheter related complication

7 DRUG INTERACTIONS As with other dialysis solutions, blood concentrations of dialyzable drugs may be reduced by dialysis. Dosage adjustment of concomitant medications may be necessary. Diabetic patients may require dosage adjustments of insulin or other treatments for hyperglycemia [see Warnings and Precautions (5.5) ] .

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy DIANEAL peritoneal dialysis solution is a pharmacologically inactive solution. While there are no adequate and well controlled studies in pregnant women, appropriate administration of DIANEAL solutions, with appropriate monitoring of hematology, electrolytes, blood chemistry and fluid status is not expected to cause fetal harm. Animal reproduction studies have not been conducted with DIANEAL solutions. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. 8.2 Lactation The components of DIANEAL solutions are excreted in human milk. 8.4 Pediatric Use Safety and effectiveness have been established based on published clinical data. No adequate and well-controlled studies have been conducted with DIANEAL solutions in pediatric patients. 8.5 Geriatric Use Safety and effectiveness have been established based on published clinical data.

12.1 Mechanism of Action DIANEAL peritoneal dialysis solutions are a pharmacologically inactive, hypertonic peritoneal dialysis solution 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 DIANEAL solutions exert an osmotic pressure across the peritoneal membrane resulting in transcapillary ultrafiltration. Like other peritoneal dialysis solutions, DIANEAL solutions contain electrolytes to facilitate the correction of electrolyte abnormalities. DIANEAL solutions contain a buffer, lactate, to help normalize acid-base abnormalities.

11 DESCRIPTION DIANEAL peritoneal dialysis solutions are sterile, nonpyrogenic solutions in flexible containers for intraperitoneal administration only. The peritoneal dialysis solutions contain no bacteriostatic or antimicrobial agents. DIANEAL solutions are hyperosmolar solutions. Table 4 - DIANEAL PD-2 and Low Calcium Peritoneal Dialysis Solution ULTRABAG Container for CAPD therapy AMBU-FLEX/Plastic Container with pull ring for APD therapy Composition/100 mL *Dextrose, Hydrous, USP Sodium Chloride, USP (NaCl) Sodium Lactate (C 3 H 5 NaO 3 ) Calcium Chloride, USP (CaCl2•2H2O) Magnesium Chloride, USP (MgCl2•6H2O) DIANEAL PD-2 1.5% Dextrose 1.5 g 538 mg 448 mg 25.7 mg 5.08 mg DIANEAL PD-2 2.5% Dextrose 2.5 g 538 mg 448 mg 25.7 mg 5.08 mg DIANEAL PD-2 4.25% Dextrose 4.25 g 538 mg 448 mg 25.7 mg 5.08 mg DIANEAL Low Calcium (2.5 mEq/L) 1.5% Dextrose 1.5 g 538 mg 448 mg 18.3 mg 5.08 mg DIANEAL Low Calcium (2.5 mEq/L) 2.5% Dextrose 2.5 g 538 mg 448 mg 18.3 mg 5.08 mg DIANEAL Low Calcium (2.5 mEq/L) 4.25% Dextrose 4.25 g 538 mg 448 mg 18.3 mg 5.08 mg Table 5 - DIANEAL Low Calcium Peritoneal Dialysis Solution Plastic container with blue pull tip for APD therapy Composition/100 mL *Dextrose, Hydrous Sodium Chloride (NaCl) Sodium Lactate (C3H5NaO3) Calcium Chloride (CaCl2•2H2O) Magnesium Chloride (MgCl2•6H2O) DIANEAL Low Calcium (2.5 mEq/L) 1.5% Dextrose 1.5 g 538 mg 448 mg 18.4 mg 5.08 mg DIANEAL Low Calcium (2.5 mEq/L) 2.5% Dextrose 2.5 g 538 mg 448 mg 18.4 mg 5.08 mg DIANEAL Low Calcium (2.5 mEq/L) 4.25% Dextrose 4.25 g 538 mg 448 mg 18.4 mg 5.08 mg The plastic container is fabricated from polyvinyl chloride (PVC Plastic). 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. The amount of water that can permeate from inside the solution container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the expiration period, e.g. di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million; however, the safety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers as well as by cell culture toxicity studies. Structural Formula Dextrose Hydrous USP

10 OVERDOSAGE There is a potential for overdose resulting in hypervolemia, hypovolemia, electrolyte disturbances or hyperglycemia. Excessive use of DIANEAL peritoneal dialysis solution with 4.25% dextrose during a peritoneal dialysis treatment can result in significant removal of water from the patient.

16 HOW SUPPLIED/STORAGE AND HANDLING DIANEAL peritoneal dialysis solutions are available in the following single-dose containers and fill volumes as shown in Tables 6-7. The solution is clear with color being slightly yellow to colorless. Table 6 - DIANEAL Peritoneal Dialysis Solutions for CAPD therapy Container Fill Volume (mL) Container Size (mL) Product Code NDC ULTRABAG Container DIANEAL PD-2 Peritoneal Dialysis Solution with 1.5% Dextrose 2000 2500 2000 3000 5B9866 5B9868 0941-0426-52 0941-0426-53 DIANEAL PD-2 Peritoneal Dialysis Solution with 2.5% Dextrose 2000 2500 2000 3000 5B9876 5B9878 0941-0427-52 0941-0427-53 DIANEAL PD-2 Peritoneal Dialysis Solution with 4.25% Dextrose 2000 2500 2000 3000 5B9896 5B9898 0941-0429-52 0941-0429-53 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 1.5% Dextrose 1500 2000 2500 2000 2000 3000 5B9765 5B9766 5B9768 0941-0424-51 0941-0424-52 0941-0424-53 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 2.5% Dextrose 1500 2000 2500 2000 2000 3000 5B9775 5B9776 5B9778 0941-0430-51 0941-0430-52 0941-0430-53 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 4.25% Dextrose 1500 2000 2500 2000 2000 3000 5B9795 5B9796 5B9798 0941-0433-51 0941-0433-52 0941-0433-53 Table 7 - DIANEAL Peritoneal Dialysis Solutions for APD therapy Container Fill Volume (mL) Container Size (mL) Product Code NDC AMBU-FLEX / Plastic Container with pull ring DIANEAL PD-2 Peritoneal Dialysis Solution with 1.5% Dextrose 1000 2000 3000 5000 6000 1000 3000 3000 6000 6000 L5B5163 L5B5166 L5B5169 L5B5193 L5B9710 0941-0411-05 0941-0411-06 0941-0411-04 0941-0411-07 0941-0411-11 DIANEAL PD-2 Peritoneal Dialysis Solution with 2.5% Dextrose 1000 2000 3000 5000 6000 1000 3000 3000 6000 6000 L5B5173 L5B5177 L5B5179 L5B5194 L5B9711 0941-0413-05 0941-0413-06 0941-0413-04 0941-0413-07 0941-0413-01 DIANEAL PD-2 Peritoneal Dialysis Solution with 4.25% Dextrose 1000 2000 3000 5000 6000 1000 3000 3000 6000 6000 L5B5183 L5B5187 L5B5189 L5B5195 L5B9712 0941-0415-05 0941-0415-06 0941-0415-04 0941-0415-07 0941-0415-01 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 1.5%Dextrose 2000 3000 5000 6000 3000 3000 6000 6000 L5B4825 L5B9901 L5B4826 L5B9770 0941-0409-06 0941-0409-05 0941-0409-07 0941-0409-01 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 2.5% Dextrose 2000 3000 5000 6000 3000 3000 6000 6000 L5B9727 L5B9902 L5B5202 L5B9771 0941-0457-08 0941-0457-02 0941-0457-05 0941-0457-01 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 4.25% Dextrose 2000 3000 5000 6000 3000 3000 6000 6000 L5B9747 L5B9903 L5B5203 L5B9772 0941-0459-08 0941-0459-02 0941-0459-05 0941-0459-01 Plastic container with blue pull tip DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 1.5% Dextrose 5000 5000 EZPB5245R 0941-0484-01 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 2.5% Dextrose 5000 5000 EZPB5255R 0941-0487-01 DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 4.25% Dextrose 5000 5000 EZPB5265R 0941-0490-01 All DIANEAL peritoneal dialysis solutions have overfills which are declared on container labeling. Freezing of solution may occur at temperatures below 0°C (32°F). Allow to thaw naturally in ambient conditions and thoroughly mix contents by shaking. Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the product be stored at room temperature (25°C/77°F): brief exposure up to 40°C (104°F) does not adversely affect the product. Store in moisture barrier overwrap and in carton until ready to use.