Voraxaze (glucarpidase) Mechanism of Action

VORAXAZE hydrolyzes METHOTREXATE (MTX) into inactive components, DAMPA and glutamate, for a nonrenal pathway of elimination1,2

MOA

5-FP, 5-formylpteroate; DAMPA, 4-deoxy-4-amino-N10-methylpteroic acid; GLU, glutamate; LV, leucovorin; MTX, methotrexate; RFC, reduced folate carrier.

Leucovorin may not be enough for patients experiencing delayed MTX clearance2

VORAXAZE lowers toxic levels in the extracellular compartment, whereas leucovorin counteracts MTX intracellularly. Only VORAXAZE rapidly reduces plasma MTX concentrations by hydrolyzing extracellular MTX.1,2

When MTX concentrations are too high, no plasma leucovorin concentration may be sufficient to ensure effective cell rescue.2

VORAXAZE rapidly cleaves MTX into 2 inactive metabolites to provide a nonrenal pathway for elimination.1,3

Watch the video to see how VORAXAZE works extracellularly.1,2

Leucovorin does not clear MTX from the body2,4

  • Leucovorin provides intracellular rescue, restoring tetrahydrofolate stores and allowing resumption of DNA and RNA synthesis, but it does not clear MTX from the body2-4
  • Leucovorin is less effective in the presence of high-circulating MTX concentrations, particularly MTX concentrations exceeding 10 µM for ≥48 hours3
  • Over-rescue with leucovorin in place of VORAXAZE is not recommended, as leucovorin is a storage vitamin and this may have implications for future rounds of HDMTX treatment3
  • HDMTX treatment failures have been reported in pediatric patients following high doses of leucovorin3

DNA, deoxyribonucleic acid; HDMTX, high-dose methotrexate; RNA, ribonucleic acid.

Learn about the differences between VORAXAZE and leucovorin
Learn about the efficacy of VORAXAZE