Consensus Guidelines strongly recommend:

Act early with Voraxaze®5

Early and rapid reduction of methotrexate (MTX) concentrations can lower the risk of irreversible damage 4,5

Recently published Consensus Guidelines recommend administration of Voraxaze® (glucarpidase) at 48 hours following initiation of high-dose methotrexate (HDMTX) therapy when MTX concentrations are above 5 μM (2.27 μg/mL) and the serum creatinine is elevated relative to the baseline measurement.4,5

Consensus Guidelines strongly recommend administration of Voraxaze® within 48 hours for optimum and effective nonrenal elimination of MTX5
Chart with hours

Administration of Voraxaze® should optimally occur within 48 to 60 hours from the start of HDMTX infusion.

Beyond 48 to 60 hours, life-threatening toxicities and even death may not be preventable.

  • When plasma MTX concentrations remain elevated following initiation of HDMTX with leucovorin rescue therapy, Voraxaze® can be initiated for rapid, nonrenal, extracellular elimination of MTX5
  • Due to its intracellular mechanism of action, leucovorin therapy may be less effective at high MTX concentrations, especially when the concentrations exceed 10 μM for 48 hours or longer5
  • MTX concentrations within 48 hours following administration of Voraxaze® can only be reliably measured by a chromatographic method1
  • DAMPA (4-deoxy-4-amino-N1>-methylpteroic acid) is an inactive metabolite of methotrexate that can interfere with the measurement of methotrexate concentration resulting in an erroneous measurement1
  • Continue to administer leucovorin after Voraxaze®. Do not administer leucovorin within 2 hours before or after a dose of Voraxaze®1


  1. Voraxaze® [prescribing information]. BTG International Inc; 2013.
  2. Howard SC, et al. Preventing and managing toxicities of high-dose methotrexate. The Oncologist 2016; 21:1-12.
  3. Widemann BC, Balis FM, Kim A, et al. Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome. J Clin Oncol. 2010; 28:3979-3986.
  4. 2013 Annual Meeting of the North American Congress of Clinical Toxicology (NACCT), Clinical Toxicology 2013; 51(7):575-724. doi:10.3109/15563650.2013.817658.
  5. Ramsey L, Balis FM, O’Brien MM, et al. Consensus guidelines for use of glucarpidase in patients with high-dose methotrexate induced acute kidney injury and delayed methotrexate clearance. Durham, NC. The Oncologist. 2017 Oct 27. doi: 10.1634/theoncologist.2017-0243
  6. Widemann BC, Adamson PC. Understanding and managing methotrexate nephrotoxicity. Oncologist. 2006;11:694-703
  7. Schwartz S, Borner K,Müller K, et al. Glucarpidase (carboxypeptidase G2) intervention in adult and elderly cancer patients with renal dysfunction and delayed methotrexate elimination after high-dose methotrexate therapy. Oncologist. 2007;12:1299-1308.
  8. Widemann BC, Balis FM, Kempf-Bielack B, et al. High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma. Cancer. 2004;100:2222-2232
  9. Data on file. BTG International Inc. 2012.
  10. de Miguel D, García-Suárez J Martín Y, Gil-Fernández JJ, Burgaleta C. Severe acute renal failure following high-dose methotrexate therapy in adults with haematological malignancies: a significant number result from unrecognized co-administration of several drugs. Nephrol Dial Transplant. 2008;23:3762-3766.
  11. Jahnke K, Korfel A, Martus P, et al; on behalf of the German Primary Central Nervous System Lymphoma Study Group (G-PCNSL-SG). High-dose methotrexate toxicity in elderly patients with primary central nervous system lymphoma. Ann Oncol. 2005;16:445-449
  12. Flombaum C, Meyers P. High-dose leucovorin as sole therapy for methotrexate toxicity. Journal of Clinical Oncology 1999; 17(5): 1589-1594.
  13. Murashima M, et al. Methotrexate clearance by high-flux hemodialysis and peritoneal dialysis: a case report. Am J Kidney Dis 2009; 53:781-874.
  14. Wall S, Johansen M, et al. Effective clearance of methotrexate using high-flux hemodialysis membranes. Am J Kidney Dis 1996; 28(6):846-854.
  15. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.
  16. Green JM. Glucarpidase to combat toxic levels of methotrexate in patients. Ther Clin Risk Manag. 2012;8:403-4
  17. Glucarpidase (Voraxaze®) National Drug Monograph and Considerations for Use. U.S. Department of Veterans Affairs website. 2014. Drug_Monograph_and_Considerations_for_Use.doc. Published June 2014. Accessed November 04, 2016.
  18. Leucovorin [prescribing information]. Bedford Laboratories; 2011.