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.
Tony Talebi, MD