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Voraxaze® and Leucovorin Work Synergistically
For patients receiving HDMTX therapy, intracellular leucovorin (LV) is critical to provide a source of tetrahydrofolates and restore DNA synthesis to prevent damage to normal cells.
However, LV does not help reduce circulating concentrations of MTX, which can remain dangerously high in patients with delayed MTX clearance due to impaired renal function.
Voraxaze® rapidly cleaves MTX into 2 inactive metabolites to provide a nonrenal pathway for elimination.1,4
Exogenous tetrahydrofolates (LV) must compete with MTX for cellular uptake via the RFC. At higher MTX concentrations, LV may be less effective.4
MTX is polyglutamated after entering cells and reversibly inhibits DHFR, leading to a significant reduction in DNA and RNA biosynthesis.4
LV provides intracellular rescue following MTX by providing a source of tetrahydrofolate to restore DNA and RNA synthesis despite ongoing inhibition of DHFR via MTX.4
Voraxaze® eliminates extracellular MTX via rapid enzymatic breakdown to nontoxic DAMPA and glutamate. Voraxaze® should be given in conjunction with LV to provide both intracellular and extracellular rescue from unwanted HDMTX toxicity.1,4
|RFC||reduced folate carrier|