Icodextrin, Sodium Chloride, Sodium Lactate, Calcium Chloride, Magnesium Chloride
FDA Drug Information • Also known as: Extraneal
- Brand Names
- Extraneal
- Route
- INTRAPERITONEAL
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION EXTRANEAL (icodextrin) Peritoneal Dialysis Solution is a solution intended for intraperitoneal administration that contains the colloid osmotic agent icodextrin. Icodextrin is a cornstarch-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 contains no bacteriostatic or antimicrobial agents. Calculated osmolarity: 282-286 mOsm/L; pH=5.0-6.0 EXTRANEAL is a sterile, nonpyrogenic, clear solution packaged in AMBU-FLEX II and ULTRABAG containers. The container systems are composed of polyvinyl 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. Image of Structural Formula of Icodextrin
What Is Icodextrin, Sodium Chloride, Sodium Lactate, Calcium Chloride, Magnesium Chloride Used For?
1 INDICATIONS AND USAGE EXTRANEAL (icodextrin) 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 kidney failure in patients requiring long-term kidney replacement therapy. EXTRANEAL 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 ( 12 ), Clinical Studies ( 14 )].
Dosage and Administration
2 DOSAGE AND ADMINISTRATION For intraperitoneal administration only. Not for intravenous or intra-arterial administration. Administer as a single daily peritoneal dialysis (PD) exchange for the long dwell. Dosage should be individualized by the prescribing physician experienced in the treatment of kidney failure in patients requiring long-term kidney replacement therapy with PD. ( 2.1 ) 2.1 Basic Dosing Information EXTRANEAL is intended for intraperitoneal administration only. Not for intravenous or intra-arterial administration. Administer 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. Administer over a period of 10 to 20 minutes at a rate that is comfortable for the patient. The mode of therapy, frequency of treatment, exchange volume, duration of dwell, and length of dialysis should be initiated and supervised by the prescribing physician experienced in the treatment of kidney failure in patients requiring long-term kidney replacement therapy 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. 2.2 Directions for Use For complete CAPD and APD system preparation, see directions accompanying ancillary equipment. Aseptic technique should be used throughout the peritoneal dialysis procedure. For single-dose only. Storage Store in moisture barrier overwrap and in carton until ready to use [see How Supplied/Storage and Handling ( 16 )] . Warming For patient comfort, EXTRANEAL can be warmed to 37°C (98.6°F). Only dry heat should be used (e.g., heating pad, warming plate). Do not immerse EXTRANEAL in water for warming. Do not use a microwave oven to warm EXTRANEAL. Do not heat above 40°C (104°F). 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. Inspect for Container Integrity and Solution Appearance Do not use EXTRANEAL if it is cloudy or discolored, if it contains particulate matter, or if the container is leaking. 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 EXTRANEAL 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 EXTRANEAL if the frangible(s) are broken or leaks are suspected as sterility may be impaired. For EXTRANEAL 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...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The most common adverse reaction (incidence > 5%) was rash. ( 6.1 ) 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 EXTRANEAL was originally studied in controlled clinical trials of 493 patients with kidney failure in patients requiring long-term kidney replacement therapy who received a single daily exchange of EXTRANEAL 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. 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. Rash was the most frequently occurring EXTRANEAL-related adverse reaction (5.5%, EXTRANEAL; 1.7% Control). Seven patients on EXTRANEAL discontinued treatment due to rash, and one patient on EXTRANEAL 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. Table 1 shows the adverse events reported in these clinical studies regardless of causality, occurring in ≥ 5% of patients and more common on EXTRANEAL than control. Table 1 - Adverse Experiences in ≥5% of Patients and More Common on EXTRANEAL 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% Clinical Laboratory Findings An increase in mean serum alkaline phosphatase has been observed in clinical studies of ESRD patients receiving EXTRANEAL. 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. Decreases in serum sodium and chloride have been observed in patients using EXTRANEAL. The mean change in serum sodium from baseline to the last study visit was -2.8 mmol/L for patients on EXTRANEAL and -0.3 mmol/L for patients on control solution. Four EXTRANEAL 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 mmol/L for EXTRANEAL 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. An apparent decrease in serum amylase activity has been observed in patients administered EXTRANEAL. 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. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post-approval use of EXTRANEAL, or in conjunction with performing the peritoneal dialysis procedure. Because these...
Drug Interactions
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. In patients using cardiac glycosides (digoxin and others), plasma levels of calcium, potassium and magnesium must be carefully monitored [see Warnings and Precautions ( 5.6 )]. Insulin: Patients with insulin-dependent diabetes may require modification of insulin dosage following initiation of treatment with EXTRANEAL. Monitor blood glucose and adjust insulin, if needed [see Warnings and Precautions ( 5.1 )] .
Contraindications
4 CONTRAINDICATIONS EXTRANEAL is contraindicated in patients with:
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary EXTRANEAL is a pharmacologically inactive solution. While there are no adequate and well controlled studies in pregnant women, appropriate administration of EXTRANEAL with monitoring of hematology, blood chemistry, and fluid status is not expected to cause fetal harm. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Overdosage
10 OVERDOSAGE No clinical trial data are available on experiences of overdosage with EXTRANEAL. 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. An increase in plasma osmolality or clinical manifestations of hypovolemia may occur. In the event of overdosage with EXTRANEAL, continued peritoneal dialysis with glucose-based solutions should be provided.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING EXTRANEAL (icodextrin) Peritoneal Dialysis Solution is available in the following containers and fill volumes: Container Fill Volume NDC ULTRABAG 2 L NDC 0941-0679-52 ULTRABAG 2.5 L NDC 0941-0679-53 AMBU-FLEX II 2 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]. Protect from freezing. Store in moisture barrier overwrap and in carton until ready to use.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.