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

Alkaline Phosphatase
An increase in mean serum alkaline phosphatase has been observed in clinical studies of ESRD patients receiving EXTRANEAL. 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.

There were individual cases where increased alkaline phosphatase was associated with elevated AST (SGOT), but neither elevation was considered causally related to treatment.

Drug Interactions

General
No clinical drug interaction studies were performed. No eva luation of EXTRANEAL’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.

Insulin
A clinical study in 6 insulin-dependent diabetic patients demonstrated no effect of EXTRANEAL on insulin absorption from the peritoneal cavity or on insulin’s ability to control blood glucose when insulin was administered intraperitoneally with EXTRANEAL. However, appropriate monitoring (See PRECAUTIONS, Drug/Laboratory Test Interactions) of blood glucose should be performed when initiating EXTRANEAL in diabetic patients and insulin dosage should be adjusted if needed (See PRECAUTIONS).

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

Antibiotics
No human drug interaction studies with antibiotics were conducted. In vitro studies eva luating 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)

Drug/Laboratory Test Interactions

Blood Glucose
Blood glucose measurement must be done with a glucose-specific method to prevent maltose interference with test results. Since falsely elevated glucose levels have been observed with blood glucose monitoring devices and test strips that use glucose dehydrogenase pyrroloquinolinequinone (GDH PQQ) or glucose-dye-oxidoreductase based methods, GDH PQQ or glucose-dye-oxidoreductase based methods should not be used to measure glucose levels in patients administered EXTRANEAL. (See WARNINGS).

Serum Amylase
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 eva luating serum amylase levels for diagnosis or monitoring of pancreatitis in patients using EXTRANEAL.

Carcinogenesis, Mutagenesis, Impairment of Fertility
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