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Voraxaze hydrolysis extracellular MTX

VORAXAZE®  rapidly REDUCES PLASMA MTX CONSENTRATIONS by hydrolysing extracellular MTX1,2


Voraxaze®  does not counteract the intracellular antioneoplastic effects of HDMTX3

  • Converts MTX to its inactive metabolites DAMPA and glutamate, metabolised by the liver3
  • Does not enter cells or cross the blood-brain barrier1,3
  • Provides an alternative route for MTX elimination in patients with renal dysfunction during HDMTX treatment3
  • Early administration may diminish the risk for serious life-treatening toxicily, and even death4

Abbreviations: 5-FP, 5-formylpteroate; DAMPA, 4-deoxy-4-amino-N10-methylpteroic acid; GLU, glutamate; HDMTX, high dose methotrexate; LV, leucovorin; MTX, methotrexate.

Leucovorin counteracts MTX intracellularly, so is less effective at high MTX concentrations1 

  • Leucovorin provides intracellular rescue (allowing resumption of DNA and RNA synthesis)1,2
  • Does not clear MTX from the body1,2
  • Completes with MTX for transport into the cell1
  • Excessive doses may impact the MTX efficacy at the next HDMTX course1

Voraxaze® and leucovorin can be used in the same patient to reduce MTX toxicity due to their different mechanism of actions, however it is recommended that they should not be administered within the 2 hours before or after each other to minimise any potential interactions3

Leucovorin Rescue Is Essential, But It Does Not Clear MTX From the Body1,2

  • Leucovorin provides intracellular rescue, restoring tetrahydrofolate stores and allowing resumption of DNA and RNA synthesis, but it does not clear MTX from the body.1,2
  • Leucovorin is less effective in the presence of high circulating MTX concentrations, particularly MTX concentrations exceeding 10 µM for ≥48 hours.1
  • Leucovorin is a storage vitamin, and excessive doses may impact future high-dose methotrexate (HDMTX) treatment courses. HDMTX treatment failures have been reported in pediatric patients following high doses of leucovorin.1