Within 15 minutes

Patients experienced rapid reductions in plasma MTX concentrations1

rapid reductions

Voraxaze® (glucarpidase) reduced plasma MTX concentrations by ≥97% within 15 minutes in all 22 treatment-evaluable patients

For up to 8 days

In clinical studies, patients treated with Voraxaze® sustained reductions in plasma MTX concentrations1

sustained restrictions
  • Results from a single-arm, open-label study in 22 treatment-evaluable patients with markedly delayed MTX clearance secondary to acute kidney injury
  • The primary endpoint of the study was the proportion of patients who achieved RSCIR in plasma MTX concentrations following initial injection
  • Of the 12 patients who failed to achieve RSCIR, 5 patients (23%) attained a transient plasma methotrexate concentration of ≤1 μmol/L

Voraxaze® delivered

Clinically important MTX
reductions in markedly less time1,12-14

LV=leucovorin, PD=peritoneal dialysis, HD=hemodialysis.

Patients can achieve clinically important reductions in plasma MTX concentrations within 15 min vs 5 to 11 days

  • LV alone: 11 ± 3 days12
  • PD + LV: 5 to 6 days13
  • High- ux HD alone: 5.5 days14
  • Voraxaze® (glucarpidase) + LV: 15 minutes1

Help lower the risk of irreversible damage3,4

Patients who received treatment with Voraxaze® (glucarpidase) ≤4 days experienced significantly lower rates of Grade 4 toxicity and mortality associated with MTX.3,4

Incidence of Grade 4 toxicity was significantly lower with early administration of Voraxaze®3

grade 4
  • Administration of Voraxaze® ≤ 96 hours after HDMTX exposure appeared to protect from the development of toxicity
  • Grade 4 toxicity developed in only 9/64 (14%) compared to 6/11 (55%) who received Voraxaze® more than 96 hours after starting HDMTX

Incidence of mortality was significantly lower with early administration of Voraxaze®4

  • Of 476 patients receiving Voraxaze®, death occurred in 22% of patients treated > 4 days of HDMTX compared to 10.9% treated within 2 days of HDMTX4
  • There are no controlled trials comparing Voraxaze® plus supportive care with supportive care measures alone in patients with toxic plasma MTX concentrations due to impaired renal function; therefore, there are no data regarding the e ect of Voraxaze® on survival or toxic death due to MTX. Voraxaze® did not prevent fatal MTX toxicity in 3% of patients in the safety population1

Safety Information1

Most common adverse reactions with Voraxaze® (glucarpidase) treatment1

Adverse reactions >1% possibly,
probably, or definitely related to Voraxaze®1*
Adverse reaction N=290, n (%)
Paresthesia 7 (2%)
Flushing 5 (2%)
Nausea/vomiting 5 (2%)
Headache 2 (1%)
Hypotension 2 (1%)

*Excluding hematologic, hepatic, or renal adverse reactions.1
This adverse reaction includes the following terms: ushing, feeling hot, burning sensation.1

  • Adverse reaction severity was rated Grade 1 or Grade 2 for all events, except for 1 patient who reported Grade 3 flushing1
  • Adverse reactions related to toxic MTX levels due to prolonged MTX clearance included myelosuppression, mucositis, acute hepatitis, and renal dysfunction and failure1

Watch the mechanism of action video:


Voraxaze® Mechanism of Action

Works in The Circulation to Quickly Clear MTX1,15-17

Effective nonrenal elimination of MTX with Voraxaze® (glucarpidase)

Mechanism of action for Voraxaze® and Leucovorin1,15-16
Product Site of action Mechanism of action
Voraxaze®1,15-16 Extracellular
  • Converts plasma MTX into inactive metabolites, thus lowering the amount of plasma MTX available to
    - Enter cells and cause toxicity
    - Further stress impaired kidneys
  • Inactive metabolites are then eliminated via nonrenal pathways
Leucovorin15,17 Intracellular
  • Protects normal cells from MTX toxicity
  • Does not affect clearance of MTX from plasma
  • Competes with MTX for the same transmembrane cellular transport system to enter the cell

Voraxaze® breaks up and removes MTX from the circulation.

Watch the mechanism of action video:

  • Voraxaze® is a recombinant bacterial enzyme that hydrolyzes the carboxyl-terminal glutamate residue from folic acid and classical antifolates such as methotrexate1
  • Voraxaze® converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate1
  • Voraxaze® provides an alternate nonrenal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment1


  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. http://www.pbm.va.gov/clinicalguidance/drugmonographs/Glucarpidase_ Drug_Monograph_and_Considerations_for_Use.doc. Published June 2014. Accessed November 04, 2016.
  18. Leucovorin [prescribing information]. Bedford Laboratories; 2011.