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…

5 WARNINGS AND PRECAUTIONS • Encapsulating peritoneal sclerosis ( 5.1 ) • Peritonitis: Initiate appropriate antimicrobial therapy ( 5.1 ) • Monitor for lactic acidosis in patients at risk ( 5.2 ) • Monitor for electrolyte, fluid, and nutrition imbalances ( 5.4 ) 5.1 Peritonitis and Encapsulating Peritoneal Sclerosis Peritonitis has been associated with DIANEAL peritoneal dialysis solution use. Following use, inspect the drained fluid for the presence of fibrin or cloudiness, which may indicate the presence of peritonitis. Improper clamping or priming sequence may result in infusion of air into the peritoneal cavity, which may result in abdominal pain and/or peritonitis. If peritonitis occurs, treat with appropriate therapy. Encapsulating Peritoneal Sclerosis (EPS), sometimes fatal, is a complication of peritoneal dialysis therapy and has been reported in patients using DIANEAL solutions. 5.2 Lactic Acidosis Monitor patients with conditions known to increase the risk of lactic acidosis [e.g., severe hypotension or sepsis that can be associated with acute renal failure, hepatic failure, inborn errors of metabolism, and treatment with drugs such as nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] before the start of treatment and during treatment with lactate-based peritoneal dialysis solutions. Use of DIANEAL solutions in patients with severe lactic acidosis is contraindicated [see Contraindications (4) ]. 5.3 Overinfusion Overinfusion of peritoneal dialysis solution volume into the peritoneal cavity may be characterized by abdominal distention, feeling of fullness and/or shortness of breath. Drain the peritoneal dialysis solution from the peritoneal cavity to treat overinfusion. 5.4 Electrolyte, Fluid, and Nutrition Imbalances Peritoneal dialysis may affect a patient’s protein, water-soluble vitamin, potassium, bicarbonate, calcium, and magnesium levels and volume status. Monitor hematology, electrolytes, blood chemistry and fluid status periodically and take appropriate clinical action. Potassium is omitted from DIANEAL solutions because dialysis may be performed to correct hyperkalemia. In situations where there is a normal serum potassium level or hypokalemia, addition of potassium chloride (up to a concentration of 4 mEq/L) to the solution may be necessary to prevent severe hypokalemia. Monitor fluid status to avoid hyper- or hypovolemia and potentially severe consequences including congestive heart failure, volume depletion and hypovolemic shock. 5.5 Hyperglycemia DIANEAL solutions contain dextrose and may increase the risk for hyperglycemia in patients with impaired glucose tolerance. Patients may require initiation or modification of antidiabetic therapy during treatment with DIANEAL solutions. Monitor blood glucose.

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

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) ] .

8.1 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.

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