FDA approves glucarpidase injection for treatment of toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function

On January 17, 2012, the U. S. Food and Drug Administration approved glucarpidase  injection (Voraxaze®, BTG International Inc.) for the treatment of toxic plasma methotrexate concentrations (> 1 μmol/L) in patients with delayed methotrexate clearance due to impaired renal function.* 

The approval was based on the pharmacodynamic endpoint of a rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, defined as an attainment of plasma methotrexate concentration less than or equal to 1 μmol/L within 15 minutes following glucarpidase administration and sustained for up to 8 days.

Efficacy was established in 22 patients with delayed methotrexate clearance (more than 2 standard deviations above the average indicated on standard nomograms) secondary to renal dysfunction.  The efficacy assessment was limited to patients having pre- and post-treatment plasma samples collected and handled according to a validated procedure to yield reliable methotrexate measurements by HPLC.

All patients received glucarpidase, 50 Units/kg, as an intravenous injection over 5 minutes. Patients with pre-glucarpidase methotrexate concentrations >100 μmol/ L were to receive a second dose of glucarpidase 48 hours after the initial dose.  All patients received vigorous intravenous hydration, urinary alkalinization, and leucovorin rescue. 


Thanks ASCO.org


Tony Talebi, MD