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EXTRANEAL
(icodextrin) Peritoneal Dialysis Solution
Dangerous Drug-Device Interaction
Only use glucose-specific monitors and test strips to measure blood glucose levels in patients using Extraneal (icodextrin) Peritoneal Dialysis Solution. Blood glucose monitoring devices using glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase (GDO)-based methods must not be used. In addition, some blood glucose monitoring systems using glucose dehydrogenase flavin-adenine dinucleotide (GDH-FAD)-based methods must not be used. Use of GDH-PQQ, GDO, and GDH-FAD-based glucose monitors and test strips has resulted in falsely elevated glucose readings (due to the presence of maltose, see Drug/Laboratory Test Interactions). Falsely elevated glucose readings have led patients or health care providers to withhold treatment of hypoglycemia or to administer insulin inappropriately. Both of these situations have resulted in unrecognized hypoglycemia, which has led to loss of consciousness, coma, permanent neurological damage, and death. Plasma levels of Extraneal (icodextrin) and its metabolites return to baseline within approximately 14 days following cessation of Extraneal (icodextrin) administration. Therefore falsely elevated glucose levels may be measured up to two weeks following cessation of Extraneal (icodextrin) therapy when GDH-PQQ, GDO, and GDH-FAD-based blood glucose monitors and test strips are used.
Because GDH-PQQ, GDO, and GDH-FAD-based blood glucose monitors may be used in hospital settings, it is important that the health care providers of peritoneal dialysis patients using Extraneal (icodextrin) carefully review the product information of the blood glucose testing system, including that of test strips, to determine if the system is appropriate for use with Extraneal (icodextrin).
To avoid improper insulin administration, educate patients to alert health care providers of this interaction whenever they are admitted to the hospital.
The manufacturers) of the monitor and test strips should be contacted to determine if icodextrin or maltose causes interference or falsely elevated glucose readings. For a list of toll free numbers for glucose monitor and test strip manufacturers, please contact the Baxter Renal Clinical Help Line 1-888-RENAL-HELP or visit www.glucosesafety.com.
Extraneal (icodextrin) Peritoneal Dialysis Solution is a peritoneal dialysis solution containing the colloid osmotic agent icodextrin. Icodextrin is a starch-derived, water-soluble glucose polymer linked by alpha (1-4) and less than 10% alpha (1-6) glucosidic bonds with a weight-average molecular weight between 13,000 and 19,000 Daltons and a number average molecular weight between 5,000 and 6,500 Daltons. The representative structural formula of icodextrin is:
 |
| Each 100 mL of Extraneal contains: | |
| Icodextrin | 7.5 g |
| Sodium Chloride, USP | 535 mg |
| Sodium Lactate | 448 mg |
| Calcium Chloride, USP | 25.7 mg |
| Magnesium Chloride, USP | 5.08 mg |
| Electrolyte content per liter: | |
| Sodium | 132 mEq/L |
| Calcium | 3.5 mEq/L |
| Magnesium | 0.5 mEq/L |
| Chloride | 96 mEq/L |
| Lactate | 40 mEq/L |
Water for Injection, USP qs
HCl/NaOH may have been used to adjust pH.
Extraneal (icodextrin peritoneal dialysis solution) contains no bacteriostatic or antimicrobial agents.
Calculated osmolarity: 282-286 mOsm/L; pH=5.0-6.0
Extraneal (icodextrin peritoneal dialysis solution) is available for intraperitoneal administration only as a sterile, nonpyrogenic, clear solution in AMBU-FLEXII, AMBU-FLEX III and ULTRABAG containers. The container systems are composed of poly vinyl chloride.
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 tissue culture toxicity studies.
Extraneal (icodextrin peritoneal dialysis solution) is indicated for a single daily exchange for the long (8- to 16- hour) dwell during continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) for the management of end-stage renal disease. Extraneal (icodextrin peritoneal dialysis solution) is also indicated to improve (compared to 4.25% dextrose) long-dwell ultrafiltration and clearance of creatinine and urea nitrogen in patients with high average or greater transport characteristics, as defined using the peritoneal equilibration test (PET) (See CLINICAL PHARMACOLOGY, Clinical Studies).
Extraneal (icodextrin peritoneal dialysis solution) is intended for intraperitoneal administration only. It should be administered only as a single daily exchange for the long dwell in continuous ambulatory peritoneal dialysis or automated peritoneal dialysis. The recommended dwell time is 8- to 16- hours.
Not for intravenous injection.
Patients should be carefully monitored to avoid under- or over-hydration. An accurate fluid balance record must be kept and the patient's body weight monitored to avoid potentially severe consequences including congestive heart failure, volume depletion, and hypovolemic shock.
Aseptic technique should be used throughout the peritoneal dialysis procedure.
To reduce possible discomfort during administration, solutions may be warmed prior to use (See Directions for Use).
Extraneal (icodextrin peritoneal dialysis solution) should be administered over a period of 10-20 minutes at a rate that is comfortable for the patient.
Do not use Extraneal (icodextrin peritoneal dialysis solution) if it is cloudy or discolored, if it contains particulate matter, or if the container is leaky.
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.
Potassium is omitted from Extraneal (icodextrin peritoneal dialysis solution) 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 to Extraneal (icodextrin peritoneal dialysis solution) was evaluated in 6 insulin-dependent diabetic patients undergoing CAPD for end stage renal disease. No interference of Extraneal (icodextrin peritoneal dialysis solution) with insulin absorption from the peritoneal cavity or with insulin's ability to control blood glucose was observed (See Drug/Laboratory Test Interactions). Appropriate monitoring of blood glucose should be performed when initiating Extraneal (icodextrin peritoneal dialysis solution) in diabetic patients and insulin dosage adjusted if needed (See PRECAUTIONS).
No human drug interaction studies with heparin were conducted. In vitro studies demonstrated no evidence of incompatibility of heparin with Extraneal (icodextrin peritoneal dialysis solution) .
No formal clinical drug interaction studies have been performed. In vitro compatibility studies with Extraneal (icodextrin) and the following antibiotics have demonstrated no effects with regard to minimum inhibitory concentration (MIC): vancomycin, cefazolin, ampicillin, ampicillin/flucoxacillin, ceftazidime, gentamicin, and amphotericin. However, aminoglycosides should not be mixed with penicillins due to chemical incompatibility.
Patients undergoing peritoneal dialysis should be under careful supervision of a physician experienced in the treatment of end-stage renal disease with peritoneal dialysis. It is recommended that patients being placed on peritoneal dialysis should be appropriately trained in a program that is under supervision of a physician.
For complete CAPD and APD system preparation, see directions accompanying ancillary equipment.
Aseptic technique should be used.
For patient comfort, Extraneal (icodextrin peritoneal dialysis solution) L can be warmed to 37°C (98°F). Only dry heat should be used. It is best to warm solutions within the overwrap using a heating pad. Do not immerse Extraneal (icodextrin peritoneal dialysis solution) in water for warming. Do not use a microwave oven to warm Extraneal (icodextrin peritoneal dialysis solution) . Heating above 40°C (104°F) may be detrimental to the solution.
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.
Inspect the container for signs of leakage and check for minute leaks by squeezing the container firmly.
Some drug additives may be incompatible with Extraneal (icodextrin peritoneal dialysis solution) . See DOSAGE AND ADMINISTRATION section for additional information. If the re-sealable rubber plug on the medication port is missing or partly removed, do not use the product if medication is to be added.
Preparation for Administration
Extraneal (icodextrin) Peritoneal Dialysis Solution is available in the following containers and fill volumes:
| Container | Fill Volume | NDC |
| ULTRABAG | 1.5 L | NDC 094 1-0679-51 |
| ULTRABAG | 2.0 L | NDC 0941-0679-52 |
| ULTRABAG | 2.5 L | NDC 0941-0679-53 |
| AMBU-FLEX III | 1.5 L | NDC 0941-0679-45 |
| AMBU-FLEX III | 2.0 L | NDC 0941-0679-47 |
| AMBU-FLEX III | 2.5 L | NDC 0941-0679-48 |
| AMBU-FLEX II | 2.0 L | NDC 0941-0679-06 |
| AMBU-FLEX II | 2.5 L | NDC 0941-0679-05 |
Each 100 mL of Extraneal contains 7.5 grams of icodextrin in an electrolyte solution with 40 mEq/L lactate.
Store at 20-25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature]. Store in moisture barrier overwrap in carton until ready to use. Protect from freezing.
Baxter Healthcare Corporation, Deerfield, IL 60015 USA. Revised: Nov 2010
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Extraneal (icodextrin peritoneal dialysis solution) was originally studied in controlled clinical trials of 493 patients with end-stage renal disease who received a single daily exchange of Extraneal (icodextrin peritoneal dialysis solution) for the long dwell (8-to 16- hours). There were 215 patients exposed for at least 6 months and 155 patients exposed for at least one year. The population was 18-83 years of age, 56% male and 44% female, 73% Caucasian, 18% Black, 4% Asian, 3% Hispanic, and it included patients with the following comorbid conditions: 27% diabetes, 49% hypertension and 23% hypertensive nephropathy.
Rash was the most frequently occurring Extraneal (icodextrin peritoneal dialysis solution) -related adverse event (5.5%, Extraneal (icodextrin peritoneal dialysis solution) ; 1.7% Control). Seven patients on Extraneal (icodextrin peritoneal dialysis solution) discontinued treatment due to rash, and one patient on Extraneal (icodextrin peritoneal dialysis solution) discontinued due to exfoliative dermatitis. The rash typically appeared within the first three weeks of treatment and resolved with treatment discontinuation or, in some patients, with continued treatment.
Female patients reported a higher incidence of skin events, including rash, in both Extraneal (icodextrin peritoneal dialysis solution) and dextrose control treatment groups.
Table 1 shows the adverse events reported in these clinical studies, regardless of causality, occurring in ≥ 5% of patients and more common on Extraneal (icodextrin peritoneal dialysis solution) than control.
Table 1 - Adverse Experiences in ≥ 5 % of Patients and More
Common on EXTRANEAL (icodextrin peritoneal dialysis solution)
| EXTRANEAL | Control | |
| N = 493 | N = 347 | |
| Peritonitis | 26% | 25% |
| Upper respiratory infection | 15% | 13% |
| Hypertension | 13% | 8% |
| Rash | 10% | 5% |
| Headache | 9% | 7% |
| Abdominal pain | 8% | 6% |
| Flu syndrome | 7% | 6% |
| Nausea | 7% | 5% |
| Cough increase | 7% | 4% |
| Edema | 6% | 5% |
| Accidental injury | 6% | 4% |
| Chest Pain | 5% | 4% |
| Dyspepsia | 5% | 4% |
| Hyperglycemia | 5% | 4% |
Adverse reactions reported with an incidence of > 5% and at least as common on dextrose control included pain, asthenia, exit site infection, infection, back pain, hypotension, diarrhea, vomiting, nausea/vomiting, anemia, peripheral edema, hypokalemia, hyperphosphatemia, hypoproteinemia, hypervolemia, arthralgia, dizziness, dyspnea, skin disorder, pruritis.
Additional adverse events occurring at an incidence of < 5% and that may or may not have been related to Extraneal (icodextrin peritoneal dialysis solution) include: pain on infusion, abdominal enlargement, cloudy effluent, ultrafiltration decrease, postural hypotension, heart failure, hyponatremia, hypochloremia, hypercalcemia, hypoglycemia, alkaline phosphatase increase, SGPT increase, SGOT increase, cramping, confusion, lung edema, facial edema, exfoliative dermatitis, eczema, vesicobullous rash, maculopapular rash, erythema multiforme. All reported events are included in the list except those already listed in Table 1 or the following two paragraphs, those not plausibly associated with Extraneal (icodextrin peritoneal dialysis solution) , and those that were associated with the condition being treated or related to the dialysis procedure.
Extraneal (icodextrin peritoneal dialysis solution) was additionally studied in a subpopulation of 92 high average/high transporter APD patients in a two-week controlled clinical trial where patients received a single daily exchange of Extraneal (icodextrin peritoneal dialysis solution) (n=47) or dextrose control (n=45) for the long dwell (14 ±2 hours). Consistent with the data reported in the original trials of Extraneal (icodextrin peritoneal dialysis solution) , rash was the most frequently occurring event.
Adverse events common to the peritoneal dialysis, including peritonitis, infection around the catheter, fluid and electrolyte imbalance, and pain, were observed at a similar frequency with Extraneal and Controls (See PRECAUTIONS).
An increase in mean serum alkaline phosphatase has been observed in clinical studies of ESRD patients receiving Extraneal (icodextrin peritoneal dialysis solution) . No associated increases in other liver chemistry tests were observed. Serum alkaline phosphatase levels did not show progressive increase over a 12-month study period. Levels returned to normal approximately two weeks after discontinuation of Extraneal (icodextrin peritoneal dialysis solution) .
Decreases in serum sodium and chloride have been observed in patients using Extraneal (icodextrin peritoneal dialysis solution) . The declines in serum sodium and chloride may be related to dilution resulting from the presence of icodextrin metabolites in plasma. Although these decreases have been small and clinically unimportant, monitoring of patients' serum electrolyte levels as part of routine blood chemistry testing is recommended.
The following adverse reactions have been identified during post-approval use of Extraneal (icodextrin peritoneal dialysis solution) . Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure. Adverse reactions are listed by MedDRA System Order Class (SOC), followed by Preferred Term in order of severity.
INFECTIONS AND INFESTATIONS: Fungal peritonitis, Peritonitis bacterial, Catheter site infection, Catheter related infection
BLOOD AND LYMPHATIC SYSTEM DISORDERS: Thrombocytopenia, Leukopenia, Leukocytosis
IMMUNE SYSTEM DISORDERS: Leukocytoclastic vasculitis, Serum sickness, Hypersensitivity
METABOLISM AND NUTRITION DISORDERS: Shock hypoglycemia, Fluid overload, Dehydration, Fluid imbalance
NERVOUS SYSTEM DISORDERS: Hypoglycemic coma, Burning sensation
EYE DISORDERS: Vision blurred
RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Bronchospasm, Stridor
GASTROINTESTINAL DISORDERS: Sclerosing encapsulating peritonitis, Aseptic peritonitis, Peritoneal cloudy effluent, Ileus, Ascites, Inguinal hernia, Abdominal discomfort
SKIN AND SUBCUTANEOUS DISORDERS: Toxic epidermal necrolysis, Erythema multiforme, Angioedema, Urticaria generalized, Toxic skin eruption, Swelling face, Periorbital edema, Exfoliative rash, Skin exfoliation, Prurigo, Rash (including macular, papular, erythematous, exfoliative), Dermatitis (including allergic and contact), Drug eruption, Erythema, Onychomadesis, Dry skin, Skin chapped, Blister
MUSCULOSKELETAL, CONNECTIVE TISSUE DISORDERS: Arthralgia, Back pain, Musculoskeletal pain
REPRODUCTIVE SYSTEM AND BREAST DISORDERS: Penile edema, Scrotal edema
GENERAL DISORDERS AND ADMINISTRATIVE SITE CONDITIONS: Discomfort, Pyrexia, Chills, Malaise, Drug effect decreased, Drug ineffective, Catheter site erythema, Catheter site inflammation, Infusion related reaction (including Infusion site pain, Instillation site pain)
There has been no observed potential of drug abuse or dependence with Extraneal (icodextrin peritoneal dialysis solution) .
No clinical drug interaction studies were performed. No evaluation of Extraneal (icodextrin peritoneal dialysis solution) 's effects on the cytochrome P450 system was conducted. 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.
A clinical study in 6 insulin-dependent diabetic patients demonstrated no effect of Extraneal (icodextrin peritoneal dialysis solution) on insulin absorption from the peritoneal cavity or on insulin's ability to control blood glucose when insulin was administered intraperitoneally with Extraneal (icodextrin peritoneal dialysis solution) . However, appropriate monitoring (See Drug/Laboratory Test Interactions) of blood glucose should be performed when initiating Extraneal (icodextrin peritoneal dialysis solution) in diabetic patients and insulin dosage should be adjusted if needed (See PRECAUTIONS).
No human drug interaction studies with heparin were conducted. In vitro studies demonstrated no evidence of incompatibility of heparin with Extraneal (icodextrin peritoneal dialysis solution) .
No human drug interaction studies with antibiotics were conducted. In vitro studies evaluating the minimum inhibitory concentration (MIC) of vancomycin, cefazolin, ampicillin, ampicillin/flucoxacillin, ceftazidime, gentamicin, and amphotericin demonstrated no evidence of incompatibility of these antibiotics with Extraneal. (See DOSAGE AND ADMINISTRATION)
Blood glucose measurement must be done with a glucose-specific method to prevent maltose interference with test results. Falsely elevated glucose levels have been observed with blood glucose monitoring devices and test strips that use glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ), glucose-dye-oxidoreductase (GDO), and some glucose dehydrogenase flavin-adenine nucleotide (GDH-FAD)-based methods. GDH-PQQ,glucose-dye-oxidoreductase, and some GDH-FAD-based methods must not be used to measure glucose levels in patients administered Extraneal (See WARNINGS).
An apparent decrease in serum amylase activity has been observed in patients administered Extraneal. Preliminary investigations indicate that icodextrin and its metabolites interfere with enzymatic-based amylase assays, resulting in inaccurately low values. This should be taken into account when evaluating serum amylase levels for diagnosis or monitoring of pancreatitis in patients using Extraneal (icodextrin peritoneal dialysis solution) .
(See Boxed Warning)
Only use glucose-specific monitors and test strips to measure blood glucose levels in patients using Extraneal (icodextrin) Peritoneal Dialysis Solution. Blood glucose monitoring devices using glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) or glucose-dye-oxidoreductase (GDO)-based methods must not be used. In addition, some blood glucose monitoring systems using glucose dehydrogenase flavin-adenine dinucleotide (GDH-FAD)-based methods must not be used. Use of GDH-PQQ, GDO, and GDH-FAD-based glucose monitors and test strips has resulted in falsely elevated glucose readings (due to the presence of maltose, see Drug/Laboratory Test Interactions). Falsely elevated glucose readings have led patients or health care providers to withhold treatment of hypoglycemia or to administer insulin inappropriately. Both of these situations have resulted in unrecognized hypoglycemia, which has led to loss of consciousness, coma, permanent neurological damage, and death. Plasma levels of Extraneal (icodextrin) and its metabolites return to baseline within approximately 14 days following cessation of Extraneal (icodextrin) administration. Therefore falsely elevated glucose levels may be measured up to two weeks following cessation of Extraneal (icodextrin) therapy when GDH-PQQ, GDO, and GDH-FAD-based blood glucose monitors and test strips are used.
Because GDH-PQQ, GDO, and GDH-FAD-based blood glucose monitors may be used in hospital settings, it is important that the health care providers of peritoneal dialysis patients using Extraneal (icodextrin) carefully review the product information of the blood glucose testing system, including that of test strips, to determine if the system is appropriate for use with Extraneal (icodextrin).
To avoid improper insulin administration, educate patients to alert health care providers of this interaction whenever they are admitted to the hospital.
The manufacturers) of the monitor and test strips should be contacted to determine if icodextrin or maltose causes interference or falsely elevated glucose readings. For a list of toll free numbers for glucose monitor and test strip manufacturers, please contact the Baxter Renal Clinical Help Line 1-888-RENAL-HELP or visit www.glucosesafety.com.
Extraneal (icodextrin peritoneal dialysis solution) is intended for intraperitoneal administration only. Not for intravenous injection.
Encapsulating peritoneal sclerosis (EPS) is a known, rare complication of peritoneal dialysis therapy. EPS has been reported in patients using peritoneal dialysis solutions including Extraneal (icodextrin). Infrequent but fatal outcomes have been reported.
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 the identification of the involved organism(s), broad-spectrum antibiotics may be indicated.
Rarely, serious hypersensitivity reactions to Extraneal (icodextrin peritoneal dialysis solution) have been reported such as toxic epidermal necrolysis, angioedema, serum sickness, erythema multiforme and leukocytoclastic vasculitis. If a serious reaction is suspected, discontinue Extraneal (icodextrin peritoneal dialysis solution) and institute appropriate treatment as clinically indicated.
Patients with severe lactic acidosis should not be treated with lactate-based peritoneal dialysis solutions (See CONTRAINDICATIONS). It is recommended that patients with conditions known to increase the risk of lactic acidosis [e.g., acute renal failure, inborn errors of metabolism, treatment with drugs such as metformin and nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)] must be monitored for 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 high.
The following conditions may predispose to adverse reactions to peritoneal dialysis procedures: abdominal conditions, including uncorrectable mechanical defects that prevent effective PD 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 should 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.
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.
Treatment should be initiated and monitored under the supervision of a physician knowledgeable in the management of patients with renal failure.
A patient's 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 patient's body weight monitored.
Significant losses of protein, amino acids, water-soluble vitamins and other medicines may occur during peritoneal dialysis. The patient's nutritional status should be monitored and replacement therapy should be provided as necessary.
In patients with hypercalcemia, particularly in those on low-calcium peritoneal dialysis solutions, consideration should be given to the fact that Extraneal (icodextrin peritoneal dialysis solution) is not provided in a low-calcium electrolyte solution.
Solutions that are cloudy, contain particulate matter, or show evidence of leakage should not be used.
Patients with insulin-dependent diabetes may require modification of insulin dosage following initiation of treatment with Extraneal (icodextrin peritoneal dialysis solution) . Appropriate monitoring of blood glucose should be performed and insulin dosage adjusted if needed (See WARNINGS; Drug/Laboratory Test Interactions).
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.
Aseptic technique should be employed throughout the procedure.
To reduce possible discomfort during administration, patients should be instructed that solutions may be warmed to 37°C (98°F) 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 Extraneal (icodextrin peritoneal dialysis solution) . Heating the solution above 40°C (104°F) may be detrimental to the solution (See DOSAGE AND ADMINISTRATION, Directions for Use).
Because the use of Extraneal (icodextrin peritoneal dialysis solution) interferes with glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ), glucose-dye-oxidoreductase (GDO), and some glucose dehydrogenase flavin-adenine dinucleotide (GDH-FAD)-based blood glucose measurements, patients must be instructed to use only glucose-specific glucose monitors and test strips (See WARNINGS; Drug/Laboratory Test Interactions).
A Patient Medication Guide is provided in each carton of Extraneal (icodextrin peritoneal dialysis solution) .
Decreases in serum sodium and chloride have been observed in patients using Extraneal (icodextrin peritoneal dialysis solution) . The mean change in serum sodium from baseline to the last study visit was -2.8 mmol/L for patients on Extraneal (icodextrin peritoneal dialysis solution) and -0.3 mmol/L for patients on control solution. Four Extraneal (icodextrin peritoneal dialysis solution) patients and two control patients developed serum sodium < 125 mmol/L. The mean change in serum chloride from baseline to last study visit was -2.0 mmol/L for Extraneal (icodextrin peritoneal dialysis solution) patients and + 0.6 mmol/L for control patients. Similar changes in serum chemistries were observed in an additional clinical study in a subpopulation of high average/high transporter patients. The declines in serum sodium and chloride may be related to dilution resulting from the presence of icodextrin metabolites in plasma. Although these decreases have been small and clinically unimportant, monitoring of the patients' serum electrolyte levels as part of routine blood chemistry testing is recommended.
Extraneal (icodextrin peritoneal dialysis solution) 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.
An increase in mean serum alkaline phosphatase has been observed in clinical studies of ESPJ) patients receiving Extraneal (icodextrin peritoneal dialysis solution) . No associated increases in liver function tests were observed. Serum alkaline phosphatase levels did not show evidence of progressive increase over a 12-month study period. Levels returned to normal approximately two weeks after discontinuation of Extraneal (icodextrin peritoneal dialysis solution) .
There were individual cases where increased alkaline phosphatase was associated with elevated AST (SGOT), but neither elevation was considered causally related to treatment.
Icodextrin did not demonstrate evidence of genotoxicity potential in in vitro bacterial cell reverse mutation assay (Ames test); in vitro mammalian cell chromosomal aberration assay (CHO cell assay); and in the in vivo micronucleus assay in rats. Long-term animal studies to evaluate the carcinogenic potential of Extraneal or icodextrin have not been conducted. Icodextrin is derived from maltodextrin, a common food ingredient.
A fertility study in rats where males and females were treated for four and two weeks, respectively, prior to mating and until day 17 of gestation at up to 1.5 g/kg/day (1/3 the human exposure on a mg/m2 basis) revealed slightly low epididymal weights in parental males in the high dose group as compared to Control. Toxicological significance of this finding was not evident as no other reproductive organs were affected and all males were of proven fertility. The study demonstrated no effects of treatment with icodextrin on mating performance, fertility, litter response, embryo-fetal survival, or fetal growth and development.
Complete animal reproduction studies including in utero embryofetal development at appreciable multiples of human exposure have not been conducted with Extraneal or icodextrin. Thus it is not known whether icodextrin or Extraneal (icodextrin peritoneal dialysis solution) solution can cause fetal harm when administered to a pregnant woman or affect reproductive capacity. Extraneal (icodextrin peritoneal dialysis solution) should only be utilized in pregnant women when the need outweighs the potential risks.
It is not known whether icodextrin or its metabolites are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Extraneal (icodextrin peritoneal dialysis solution) is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
No formal studies were specifically carried out in the geriatric population. However, 140 of the patients in clinical studies of Extraneal (icodextrin peritoneal dialysis solution) were age 65 or older, with 28 of the patients age 75 or older. No overall differences in safety or effectiveness were observed between these patients and patients under age 65. Although clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
No data are available on experiences of overdosage with Extraneal (icodextrin peritoneal dialysis solution) . Overdosage of Extraneal would be expected to result in higher levels of serum icodextrin and metabolites, but it is not known what signs or symptoms might be caused by exposure in excess of the exposures used in clinical trials. In the event of overdosage with Extraneal (icodextrin peritoneal dialysis solution) , continued peritoneal dialysis with glucose-based solutions should be provided.
Extraneal (icodextrin) is contraindicated in patients with a known allergy to cornstarch or icodextrin, in patients with maltose or isomaltose intolerance, in patients with glycogen storage disease, and in patients with pre-existing severe lactic acidosis.
Extraneal (icodextrin peritoneal dialysis solution) is an isosmotic peritoneal dialysis solution containing glucose polymers (icodextrin) as the primary osmotic agent. Icodextrin functions as a colloid osmotic agent to achieve
ultrafiltration during long peritoneal dialysis dwells. Icodextrin acts in the peritoneal cavity by exerting osmotic pressure across small intercellular pores resulting in transcapillary ultrafiltration throughout the dwell. Like other peritoneal dialysis solutions, Extraneal (icodextrin peritoneal dialysis solution) also contains electrolytes to help normalize electrolyte balance and lactate to help normalize acid-base status.
Absorption of icodextrin from the peritoneal cavity follows zero-order kinetics consistent with convective transport via peritoneal lymphatic pathways. In a single-dose pharmacokinetic study using Extraneal (icodextrin), a median of 40% (60 g) of the instilled icodextrin was absorbed from the peritoneal solution during a 12-hour dwell. Plasma levels of icodextrin rose during the dwell and declined after the dwell was drained. Peak plasma levels of icodextrin plus its metabolites (median Cpeak 2.2g/L) were observed at the end of the long dwell exchange (median T^ = 13 hours).
At steady-state, the mean plasma level of icodextrin plus its metabolites was about 5 g/L. In multidose studies, steady-state levels of icodextrin were achieved within one week. Plasma levels of icodextrin and metabolites return to baseline values within approximately two weeks following cessation of icodextrin administration.
Icodextrin is metabolized by alpha-amylase into oligosaccharides with a lower degree of polymerization (DP), including maltose (DP2), maltotriose (DPS), maltotetraose (DP4), and higher molecular weight species. In a single dose study, DP2, DPS and DP4 showed a progressive rise in plasma concentrations with a profile similar to that for total icodextrin, with peak values reached by the end of the dwell and declining thereafter. Only very small increases in blood levels of larger polymers were observed. Steady-state plasma levels of icodextrin metabolites were achieved within one week and stable plasma levels were observed during long-term administration.
Some degree of metabolism of icodextrin occurs intraperitoneally with a progressive rise in the concentration of the smaller polymers in the dialysate during the 12-hour dwell.
Icodextrin undergoes renal elimination in direct proportion to the level of residual renal function. Diffusion of the smaller icodextrin metabolites from plasma into the peritoneal cavity is also possible after systemic absorption and metabolism of icodextrin.
The influence of age on the pharmacokinetics of icodextrin and its metabolites was not assessed.
The influence of gender and race on the pharmacokinetics of icodextrin and its metabolites was not assessed.
Extraneal (icodextrin peritoneal dialysis solution) has demonstrated efficacy as a peritoneal dialysis solution in clinical trials of approximately 480 patients studied with end-stage renal disease (ESRD).
In the active-controlled trials of one to six months in duration, described below, Extraneal (icodextrin peritoneal dialysis solution) used once-daily for the long dwell in either continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD) therapy resulted in higher net ultrafiltration than 1.5% and 2.5% dextrose solutions, and higher creatinine and urea nitrogen clearances than 2.5% dextrose. Net ultrafiltration was similar to 4.25% dextrose across all patients in these studies. Effects were generally similar in CAPD and APD.
In an additional randomized, multicenter, active-controlled two-week study in high average/high transporter APD patients, Extraneal (icodextrin peritoneal dialysis solution) used once daily for the long dwell produced higher net ultrafiltration compared to 4.25% dextrose. Mean creatinine and urea nitrogen clearances were also greater with Extraneal (icodextrin peritoneal dialysis solution) and ultrafiltration efficiency was improved.
In 175 CAPD patients randomized to Extraneal (icodextrin peritoneal dialysis solution) (N=90) or 2.5% dextrose solution (N=85) for the 8-15 hour overnight dwell for one month, mean net ultrafiltration for the overnight dwell was significantly greater in the Extraneal (icodextrin peritoneal dialysis solution) group at weeks 2 and 4 (Figure 1). Mean creatinine and urea nitrogen clearances were also greater with Extraneal (icodextrin peritoneal dialysis solution) (Figure 2).
Figure 1 - Mean Net Ultrafiltration for the Overnight Dwell
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Figure 2 - Mean Creatinine and Urea Nitrogen Clearance for
the Overnight Dwell
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In another study of 39 APD patients randomized to Extraneal (icodextrin peritoneal dialysis solution) or 2.5% dextrose solution for the long, daytime dwell (10-17 hours) for three months, the net ultrafiltration reported during the treatment period was (mean ± SD) 278 ± 192 mL for the Extraneal (icodextrin peritoneal dialysis solution) group and -138 ± 352 mL for the dextrose group (p < 0.001). Mean creatinine and urea nitrogen clearances were significantly greater for Extraneal (icodextrin peritoneal dialysis solution) than 2.5% dextrose at weeks 6 and 12 (p < 0.001).
In a six-month study in CAPD patients comparing Extraneal (icodextrin peritoneal dialysis solution) (n=28) with 4.25% dextrose (n=31), net ultrafiltration achieved during an 8-hour dwell averaged 510 mL for Extraneal (icodextrin peritoneal dialysis solution) and 556 mL for 4.25% dextrose. For 12-hour dwells, net ultrafiltration averaged 575 mL for Extraneal (icodextrin peritoneal dialysis solution) (n=29) and 476 mL for 4.25% dextrose (n=31). There was no significant difference between the two groups with respect to ultrafiltration.
In a two week study in high average/high transporter APD patients (4-hour D/P creatinine ratio > 0.70 and a 4-hour D/D0 ratio < 0.34, as defined by the peritoneal equilibration test (PET)), comparing Extraneal (icodextrin peritoneal dialysis solution) (n=47) to 4.25% dextrose (n=45), after adjusting for baseline, the mean net ultrafiltration achieved during a 14 ± 2 hour dwell was significantly greater in the Extraneal (icodextrin peritoneal dialysis solution) group than the 4.25% dextrose group at weeks 1 and 2 (p < 0.001, see Figure 3). Consistent with increases in net ultrafiltration, there were also significantly greater creatinine and urea nitrogen clearances and ultrafiltration efficiency in the Extraneal (icodextrin peritoneal dialysis solution) group (p < 0.001, see Figure 3).
Figure 3 - Mean Net Ultrafiltration, Creatinine and Urea
Nitrogen Clearances and Ultrafiltration Efficiency for the Long Dwell in High
Average/High Transporter Patients
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Peritoneal Membrane Transport Characteristics: After one year of treatment with Extraneal (icodextrin peritoneal dialysis solution) during the long dwell exchange, there were no differences in membrane transport characteristics for urea and creatinine. The mass transfer area coefficients (MTAC) for urea, creatinine, and glucose at one year were not different in patients receiving treatment with Extraneal (icodextrin peritoneal dialysis solution) or 2.5% dextrose solution for the long dwell.
MEDICATION GUIDE
Extraneal
(X-tra-neel)
(icodextrin) Peritoneal Dialysis Solution
Read the Medication Guide that comes with Extraneal (icodextrin peritoneal dialysis solution) before you begin treatment and each time you receive a carton of Extraneal (icodextrin peritoneal dialysis solution) . There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.
What is the most important information I should know about Extraneal?
Extraneal (icodextrin) contains maltose, which can react with certain blood glucose (blood sugar) monitors and test strips.
What is Extraneal (icodextrin peritoneal dialysis solution) ?
Extraneal (icodextrin peritoneal dialysis solution) is a prescription peritoneal dialysis solution. Extraneal (icodextrin peritoneal dialysis solution) draws fluid and wastes from your bloodstream into your peritoneal cavity (the space inside your abdomen). The fluids and wastes are removed from your body when the Extraneal (icodextrin peritoneal dialysis solution) solution is drained.
Extraneal (icodextrin peritoneal dialysis solution) is for the long dwell exchange (8 hours to 16 hours) in peritoneal dialysis. The long dwell is the exchange that lasts 8 hours or more:
Extraneal (icodextrin peritoneal dialysis solution) is not for intravenous injection (injection into a vein). It is not known if Extraneal (icodextrin peritoneal dialysis solution) is safe and works in children.
Who should not use Extraneal (icodextrin peritoneal dialysis solution) ?
Do not use Extraneal (icodextrin peritoneal dialysis solution) if:
What should I tell my doctor before using Extraneal (icodextrin peritoneal dialysis solution) ?
Extraneal (icodextrin peritoneal dialysis solution) may not be right for you. Before using Extraneal (icodextrin peritoneal dialysis solution) , tell your doctor about all your medical conditions, including if you:
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. The dose of certain medicines may need to be changed when you use Extraneal (icodextrin peritoneal dialysis solution) . Especially tell your doctor if you take:
Know the medicines you take. Keep a list of them and show your doctor and pharmacist when you get a new medicine.
How should I use Extraneal (icodextrin peritoneal dialysis solution) ?
Follow the steps that you learned in your peritoneal dialysis training to do your Extraneal (icodextrin peritoneal dialysis solution) exchange.
What are possible side effects of Extraneal (icodextrin peritoneal dialysis solution) ?
See “What is the most important information I should know about Extraneal (icodextrin peritoneal dialysis solution) ?”
Common side effects of Extraneal (icodextrin peritoneal dialysis solution) include:
These are not all the possible side effects of Extraneal (icodextrin peritoneal dialysis solution) . For more information, ask your doctor or dialysis center.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Extraneal (icodextrin peritoneal dialysis solution) ?
General information about Extraneal (icodextrin peritoneal dialysis solution)
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Extraneal (icodextrin peritoneal dialysis solution) for a condition for which it was not prescribed. Do not give Extraneal (icodextrin peritoneal dialysis solution) to other people, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about Extraneal (icodextrin peritoneal dialysis solution) . If you would like more information, talk with your doctor. You can ask your doctor for information about Extraneal (icodextrin peritoneal dialysis solution) that is written for healthcare professionals. You can also find out more about Extraneal (icodextrin peritoneal dialysis solution) by calling your doctor or visiting the website www.renalinfo.com.
