Clinical outcomes after transition from weight-based to fixed-dose glucarpidase for high-dose methotrexate toxicity at a large academic medical center.

Authors

Melissa L Bastacky, Mario Martinez, Shrina Duggal, Gina Lamm, Henry Thorpe, Jan Drappatz, Megan M Mantica

Published in

Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. Pages 10781552261462075. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

IntroductionDelayed methotrexate clearance can result in life-threatening toxicities including renal failure. Treatment includes vigorous hydration, urine alkalinization, leucovorin rescue, and glucarpidase. While traditional glucarpidase dosing is weight-based, its pharmacokinetic properties support possible use of non-weight-based dosing strategies. We evaluated clinical outcomes after transition from weight-based to fixed-dose glucarpidase for high-dose methotrexate (HDMTX) toxicity at a large academic medical center.MethodsAdult patients requiring inpatient glucarpidase for HDMTX-associated renal insufficiency between October 2014 and June 2025 were retrospectively reviewed. Patients receiving weight-based glucarpidase prior to implementation of a fixed 2000-unit dosing strategy were included for comparison. The primary objective was to compare time to renal recovery. Secondary outcomes were exploratory and included time to glucarpidase administration, peak serum creatinine (Scr) fold-change, dialysis requirement, and hospital length of stay (LOS).ResultsFourteen patients were included for analysis. Time to renal recovery was nearly identical between groups. The fixed-dose group received glucarpidase significantly sooner after HDMTX compared to the weight-based group (median 45.1 h vs. 71.5 h, p = 0.015) and had significantly lower max fold change in Scr (median 2.8-fold vs 3.8-fold, p = 0.034). The need for dialysis and median LOS trended towards fewer patients requiring dialysis (n = 0 vs n = 4, p = 0.070) and shorter LOS (19.1 days vs 39.3 days, p = 0.074) for the fixed-dose group.ConclusionsTransitioning from a weight-based to 2000-unit fixed-dose for glucarpidase at our institution resulted in sustained efficacy and safety. Further research is necessary to define optimal glucarpidase dosing.

PMID:
42423543
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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