ished.
8.5 Geriatric Use
No formal studies were specifically carried out in the geriatric population. However, 140 of the patients in clinicalstudies of EXTRANEAL were age 65 or older, with 28 of the patients age 75 or older. No overall differences insafety or effectiveness were observed between these patients and patients under age 65. Although clinical experiencehas not identified differences in responses between the elderly and younger patients, greater sensitivity of someolder individuals cannot be ruled out.
10. OVERDOSAGE
No clinical trial data are available on experiences of overdosage with EXTRANEAL. Overdosage of EXTRANEALwould be expected to result in higher levels of serum icodextrin and metabolites, but it is not known what signs orsymptoms might be caused by exposure in excess of the exposures used in clinical trials. An increase in plasmaosmolality or clinical manifestations of hypovolemia may occur. In the event of overdosage with EXTRANEAL,continued peritoneal dialysis with glucose-based solutions should be provided.
11. DESCRIPTION
EXTRANEAL (icodextrin) Peritoneal Dialysis Solution is a solution intended for intraperitoneal administration thatcontains the colloid osmotic agent icodextrin. Icodextrin is a starch-derived, water-soluble glucose polymer linkedby 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. Therepresentative 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 smallamounts within the expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million; however, thesafety of the plastic has been confirmed in tests in animals according to USP biological tests for plastic containers aswell as by tissue culture toxicity studies.
12. CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
EXTRANEAL is an isosmotic peritoneal dialysis solution containing glucose polymers (icodextrin) as the primaryosmotic agent. Icodextrin functions as a colloid osmotic agent to achieve ultrafiltration during long peritonealdialysis dwells. Icodextrin acts in the peritoneal cavity by exerting osmotic pressure across small intercellular poresresulting in transcapillary ultrafiltration throughout the dwell. Like other peritoneal dialysis solutions,EXTRANEAL also contains electrolytes to help normalize electrolyte balance and lactate to help normalize acidbasestatus.
12.2 Pharmacodynamics
EXTRANEAL results in a reduction in the absorbed caloric (carbohydrate) load compared to 4.25% hyperosmolarglucose solutions. Additionally, EXTRANEAL results i |
