Baxter 5B5202 - SOLUTION, DIANEAL LOW CALCIUM 500 ML PD, 2/CS

Baxter 5B5202 - SOLUTION, DIANEAL LOW CALCIUM 500 ML PD, 2/CS

DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis Solution with 2.5% Dextrose AMBU-FLEX III CONTAINER

DIANEAL Peritoneal Dialysis Solutions are sterile, nonpyrogenic solutions in AMBU-FLEX and ULTRABAG containers for intraperitoneal administration only. The peritoneal dialysis solutions contain no bacteriostatic or antimicrobial agents. Composition, calculated osmolarity, pH, and ionic concentrations are shown in Table A. DIANEAL is a hyperosmolar solution.

Table A

The plastic container is fabricated from polyvinyl chloride (PL 146 Plastic). Exposure to temperatures above 25?/77? 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.

Clinical Pharmacology

Mechanism of Action

DIANEAL is a 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 exerts an osmotic pressure across the peritoneal membrane resulting in transcapillary ultrafiltration. Like other peritoneal dialysis solutions, DIANEAL contains electrolytes to facilitate the correction of electrolyte abnormalities. DIANEAL contains a buffer, lactate, to help normalize acid-base abnormalities.

Pharmacokinetics of DIANEAL

Glucose content in DIANEAL is expressed as dextrose monohydrate and is available in three concentrations: 1.5%, 2.5% and 4.25%.

Glucose is rapidly absorbed from the peritoneal cavity by diffusion and appears quickly in the circulation due to the high glucose concentration gradient between DIANEAL compared to blood capillary glucose level. Absorption per unit time will be the highest at the start of an exchange and decreases over time. The rate of glucose absorption will be dependent upon the transport characteristics of the patient's peritoneal membrane as determined by a peritoneal equilibration test (PET). Glucose absorption will also depend upon the concentration of glucose used for the exchange and the length of the dwell. Glucose is metabolized by normal cellular pathways (e.g. glycolysis) and provides a source of calories and may elevate blood glucose levels.

Transport of other molecules across the peritoneal membrane, such as lactate, will occur by diffusion. Metabolism of lactate occurs in the liver and results in the generation of the bicarbonate. Transport of other molecules will be dependent upon the molecular size of the solute, the concentration gradient, and the effective peritoneal surface area as determined by the PET.

Indications and Usage

DIANEAL peritoneal dialysis solutions are indicated for patients in acute or chronic renal failure when nondialytic medical therapy is judged to be inadequate.

Contraindications

DIANEAL is contraindicated in patients with pre-existing severe lactic acidosis.

Warnings

Encapsulating Peritoneal Sclerosis (EPS) is considered to be a known, rare complication of peritoneal dialysis therapy. EPS has been reported in patients using peritoneal dialysis solutions including DIANEAL. Infrequently, fatal outcomes of EPS have been reported with DIANEAL.

Patients with severe lactic acidosis should not be treated with lactate-based peritoneal dialysis solutions (See Contraindications). Patients with conditions known to increase the risk of lactic acidosis [e.g., acute renal failure, hepatic failure, inborn errors of metabolism, treatment with drugs such as metformin, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), and sepsis/shock] must be monitored for the occurrence of lactic acidosis before the start of treatment and during treatment with lactate-based peritoneal dialysis solutions.

When prescribing the solution to be used for an individual patient, consideration should be given to the potential interaction between the dialysis treatment and therapy directed at other existing illnesses. Serum potassium levels should be monitored carefully in patients treated with cardiac glycosides. For example, rapid potassium removal may create arrhythmias in cardiac patients using digitalis or similar drugs; digitalis toxicity may be masked by hyperkalemia, hypermagnesemia, or hypocalcemia. Correction of electrolytes by dialysis may precipitate signs and symptoms of digitalis excess. Conversely, toxicity may occur at suboptimal dosages of digitalis if potassium is low or calcium is high.

Diabetics require careful monitoring of insulin requirements and other treatments for hyperglycemia during and following dialysis with dextrose containing solutions.

Precautions

General
Peritoneal-Dialysis Related

DIANEAL is intended for intraperitoneal administration only. Not for intravenous administration.

The following conditions may predispose to adverse reactions to peritoneal dialysis procedures: abdominal conditions, including uncorrectable mechanical defects that prevent effective peritoneal dialysis or increase the risk of infection, disruption of the peritoneal membrane and diaphragm by surgery, congenital anomalies or trauma prior to complete healing, abdominal tumors, abdominal wall infections, hernias, fecal fistula, colostomies or ileostomies, frequent episodes of diverticulitis, inflammatory or ischemic bowel disease, large polycystic kidneys, or other conditions that compromise the integrity of the abdominal wall, abdominal surface, or intra-abdominal cavity, such as documented loss of peritoneal function or extensive adhesions that compromise peritoneal function. Conditions that preclude normal nutrition, impaired respiratory function, recent aortic graft placement, and potassium deficiency may also predispose to complications of peritoneal dialysis.

Aseptic technique must be employed throughout the peritoneal dialysis procedure to reduce the possibility of infection.

Following use, the drained fluid should be inspected for the presence of fibrin or cloudiness, which may indicate the presence of peritonitis.

If peritonitis occurs, the choice and dosage of antibiotics should be based upon the results of identification and sensitivity studies of the isolated organism(s) when possible. Prior to identification of the involved organism(s), broad-spectrum antibiotics may be indicated.

Overinfusion of peritoneal dialysis solution volume into the peritoneal cavity may be characterized by abdominal distention, feeling of fullness and/or shortness of breath. Treatment of overinfusion is to drain the peritoneal dialysis solution from the peritoneal cavity.

Need for Trained Physician

Treatment should be initiated and monitored under the supervision of a physician knowledgeable in the management of patients with renal failure.

A patients volume status should be carefully monitored to avoid hyper- or hypovolemia and potentially severe consequences including congestive heart failure, volume depletion and hypovolemic shock. An accurate fluid balance record must be kept and the patients body weight monitored. Excessive use of DIANEAL peritoneal dialysis solution with higher dextrose concentration during a peritoneal dialysis treatment may result in significant removal of water from the patient (see Dosage and Administration).

Significant losses of protein, amino acids, water-soluble vitamins and other medicines may occur during peritoneal dialysis. The patients nutritional status should be monitored and replacement therapy should be provided as necessary.

Information for Patients

Patients should be instructed not to use solutions if they are cloudy, discolored, contain visible particulate matter, or if they show evidence of leaking containers (see Dosage and Administration).

Aseptic technique must be employed throughout the procedure.

An improper clamping sequence may result in infusion of air into the peritoneum (see Dosage and Administration, Directions for Use).

To reduce possible discomfort during administration, patients should be instructed that solutions may be warmed to 37? (98?) prior to use. Only dry heat should be used. It is best to warm solutions within the overwrap using a heating pad. To avoid contamination, solutions should not be immersed in water for warming. Do not use a microwave oven to warm the solution (see Dosage and Administration, Directions for Use).

Laboratory Tests

Serum Electrolytes

DIANEAL does not contain potassium. Evaluate serum potassium prior to administering potassium chloride to the patient. 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. This should be made under careful evaluation of serum and total body potassium, and only under the direction of a physician.

Fluid, hematology, blood chemistry, electrolyte concentrations, and bicarbonate should be monitored periodically. If serum magnesium levels are low, magnesium supplements may be used.

Patients receiving DIANEAL solutions should have their calcium levels monitored for the development of hypocalcemia or hypercalcemia. In these circumstances, adjustments to the dosage of the phosphate binders, vitamin D analogs, and/or calcimimetics should be considered by the physician. DIANEAL Low Calcium (2.5 mEq/L) Peritoneal Dialysis solution should be considered for use in patients with hypercalcemia.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to evaluate the carcinogenic or mutagenic potential of this product, or its potential to affect fertility adversely, have not been performed.

Drug Interactions

No clinical drug interaction studies were performed. As with other dialysis solutions, blood concentrations of dialyzable drugs may be reduced by dialysis. Dosage adjustment of concomitant medications may be necessary. In patients using cardiac glycosides (digoxin and others), plasma levels of calcium, potassium and magnesium must be carefully monitored (see Warnings).

Use in Specific Population

Pregnancy

Pregnancy Category C. DIANEAL is a peritoneal dialysis solution of electrolytes, lactate and dextrose and is pharmacologically inactive. Animal reproduction studies have not been conducted with DIANEAL dialysis solution. While there are no adequate and well controlled studies in pregnant women, appropriate administration of DIANEAL with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to cause fetal harm, or affect reproductive capacity. Maintenance of normal acid-base balance is important for fetal well being. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing DIANEAL.

Nursing Mothers

DIANEAL is a dialysis solution of electrolytes, lactate and dextrose and is pharmacologically inactive. The components of DIANEAL are excreted in human milk. Appropriate administration of DIANEAL with monitoring of fluid, electrolyte, acid-base and glucose balance, is not expected to harm a nursing infant. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing DIANEAL.

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.

Geriatric Use

Safety and effectiveness have been established based on published clinical data.

Adverse Reactions

The following adverse reactions have been identified during post approval use of DIANEAL. 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 during drug exposure. Adverse reactions are listed by MedDRA System Organ Class (SOC), then by Preferred Term in order of severity.

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

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.

Dosage and Administration

DIANEAL peritoneal dialysis solutions are intended for intraperitoneal administration only.

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 and supervising the treatment of the individual patient. DIANEAL should be administered at a rate that is comfortable for the patient, generally over a period of 10-20 minutes for a single exchange.

Patients on continuous ambulatory peritoneal dialysis (CAPD) typically perform 4 cycles per day (24 hours). Patients on automated peritoneal dialysis (APD) typically perform 4-5 cycles at night and up to 2 cycles during the day. The fill volume depends on body size, usually from 2.0 to 2.5 liters per 1.73m².

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 patients body weight becomes closer to the ideal dry weight, lowering the dextrose concentration of DIANEAL 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.

• Solutions that are cloudy, discolored, contain visible particulate matter, or show evidence of leakage should not be used.
• Following use, the drained fluid should be inspected for the presence of fibrin or cloudiness which may indicate the presence of peritonitis.
• For single use only. Discard unused portion.
• It is recommended that patients being placed on peritoneal dialysis and/or their caretaker(s) should be appropriately trained.

Addition of Potassium

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, the addition of potassium chloride (up to a concentration of 4 mEq/L) may be indicated to prevent severe hypokalemia. The decision to add potassium chloride should be made by the physician after careful evaluation of serum potassium.

Addition of Insulin

Patients with insulin-dependent diabetes may require modification of insulin dosage following initiation of treatment with DIANEAL. Appropriate monitoring of blood glucose should be performed when initiating DIANEAL in diabetic patients and insulin dosage adjusted if needed (see Warnings).

Addition of Heparin

No human drug interaction studies with heparin were conducted. In vitro studies demonstrated no evidence of incompatibility of heparin with DIANEAL.

Addition of Antibiotics

No formal clinical drug interaction studies have been performed. In vitro studies of the following medications have demonstrated stability with DIANEAL: amphotericin B, ampicillin, cefazolin, cefepime, cefotaxime, ceftazidime, ceftriaxone, ciprofloxacin, clindamycin, deferoxamine, erythromycin, gentamicin, linezolid, mezlocillin, miconazole, moxifloxacin, nafcillin, ofloxacin, penicillin G, piperacillin, sulfamethoxazole/trimethoprim, ticarcillin, tobramycin, and vancomycin. However, aminoglycosides should not be mixed with penicillins due to chemical incompatibility.

Warming

For patient comfort, DIANEAL can be warmed to 37? (98?). Only dry heat should be used. It is best to warm solutions within the overwrap using a heating pad. Do not immerse DIANEAL in water for warming. Do not use a microwave oven to warm DIANEAL.

To Open

To open, tear the overwrap down at the slit and remove the solution container. 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 for Container Integrity

Inspect the patient connector to ensure the pull ring is attached. Do not use if pull ring is not attached to the connector. Inspect the DIANEAL 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 if the frangible(s) are broken or leaks are suspected as sterility may be impaired.

For DIANEAL in UltraBag, 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.

Adding Medications

Some drug additives may be incompatible with DIANEAL. See DOSAGE AND ADMINISTRATION section for additional information. 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.

• Put on mask. Clean and/or disinfect hands.
• Prepare medication port site using aseptic technique.
• Using a syringe with a 1-inch long, 25- to 19-gauge needle, puncture the medication port and inject additive.
• Reposition container with container ports up and evacuate medication port by squeezing and tapping it.
• Mix solution and additive thoroughly.

Administration

• Put on mask. Clean and/or disinfect hands.
• Place DIANEAL on work surface.
• For UltraBag system for manual exchange, uncoil tubing and drain bag. Ensure the patient transfer set is closed. Break the connector (Y-set) frangible.
• Remove pull ring from connector of solution container. Once the pull ring has been removed do not reuse the solution or container.
• Immediately attach the solution container to patient connector (transfer set) or appropriate peritoneal dialysis set.
• For Ambu-Flex, continue with therapy as instructed in user manual or directions accompanying tubing sets for automated peritoneal dialysis.
• For UltraBag, follow the below steps:
• Clamp solution line and then break frangible near solution bag. Hang solution container and place the drainage container below the level of the abdomen.
• Open transfer set to drain the solution from abdomen. If drainage cannot be established, contact your clinician. When drainage complete, close transfer set.
• Remove clamp from solution line and flush new solution to flow into the drainage container for 5 seconds to prime the line. Clamp drain line after flush complete.
• Open transfer set to fill. When fill complete, close transfer set.
• Disconnect UltraBag from transfer set and apply MiniCap.
• Upon completion of therapy, discard any unused portion.