Resources
MTXPK.org TOOL
MTXPK.org is a free, open-access online tool designed to help clinicians understand the pharmacokinetics of HDMTX, especially regarding delayed clearance.*
- Know when to expect your patient’s MTX concentration to reach a level acceptable for discharge1
- Evaluate your patient’s expected MTX clearance1
- Compare your patient’s MTX clearance with the population mean and 2 SDs above the mean1
- See how your patient’s MTX levels compare with levels known to confer risk for serious MTX toxicity based on expert consensus guidelines1
- Evaluate SCr trend1
- Identify delayed MTX clearance timely, allowing you to act within the critical treatment window of 48-60 hours to lower circulating MTX levels and facilitate renal recovery1-3
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*
This tool is a reference aid and the information contained is not intended to be a substitute for the exercise of professional judgment.
VORAXAZE is indicated in patients with all of the following4:
MTX levels >2 SDs above the mean MTX excretion curve
MTX levels >1 μmol/L
SCr trend line indicating impaired renal function
VORAXAZE is not recommended for patients with expected MTX clearance and plasma concentrations, as use may result in subtherapeutic exposure of MTX.4
AUC, area under curve; HDMTX, high-dose methotrexate; MTX, methotrexate; SCr, serum creatinine; SD, standard deviation.
In patients with impaired renal function and delayed MTX clearance, plasma MTX levels associated with severe toxicity may include5:
>5-10µM
24 hours
>1µM
48 hours
These MTX concentrations are provided for clinical context. VORAXAZE is indicated in patients with toxic MTX levels (>1 µM) with delayed MTX clearance due to impaired renal function.4
MTXPK.org Tutorial Video
A brief tutorial that walks you step by step through the process of using MTXPK.org.*
MTXPK.org: A Clinical Decision Support Tool Evaluating High‐Dose Methotrexate Pharmacokinetics to Inform Post‐Infusion Care and Use of Glucarpidase
Overview of the web-based clinical decision support tool, MTXPK.org, that helps clinicians understand the pharmacokinetics of HDMTX, especially regarding delayed clearance.*
A Methotrexate Dashboard: Integrating MTXPK.org Into the Electronic Health Record to Facilitate Model-Informed Care for Pediatric Patients Receiving High-Dose Methotrexate
This article highlights how translational informatics can advance, automate, and enhance the usability of clinical decision support tools by embedding MTXPK.org within the electronic health record.
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*
This tool is a reference aid and the information contained is not intended to be a substitute for the exercise of professional judgment.
Guidelines
Consensus Guidelines for VORAXAZE Use
Review the consensus guidelines for use of glucarpidase in patients with HDMTX-induced AKI and delayed MTX clearance.
Expert Consensus Stocking Guidelines
Review the stocking guidelines established by an international expert panel.
Educational and Downloadable Tools
VORAXAZE (glucarpidase) for Treatment of High-Dose Methotrexate Toxicity
Download this resource for an overview of the largest and only controlled study evaluating the effect of glucarpidase on clinical outcomes in patients with HDMTX-induced AKI.
HDMTX Management Summary Sheet
Download this resource to identify and treat promptly when high-dose MTX-induced acute kidney injury presents.
O'Donoghue, et al. 2022 Summary Sheet
Learn about complications from sustained toxic methotrexate concentrations and how to anticipate and detect delayed MTX clearance early.
VORAXAZE and Leucovorin Differentiator Summary
Learn about the unique roles of VORAXAZE and leucovorin in managing methotrexate toxicity in patients with delayed clearance due to renal impairment.
Kidney Function and Acute Kidney Injury Summary
Learn about monitoring patients for high-dose methotrexate-induced acute kidney injury.
Patient Testimonial
Matthew’s Story: A Race Against the Clock
Hear Matthew’s story of how VORAXAZE was ordered, delivered, and administered in his time of need.
HCP Testimonials
Mitigating Methotrexate Toxicity With VORAXAZE in Osteosarcoma
Hear Dr. Matteo Trucco discuss the importance and risks of methotrexate in methotrexate, adriamycin, and platinol (MAP) chemotherapy and how VORAXAZE effectively counters methotrexate toxicity, preventing further toxicity.
Completing MAP Chemotherapy and the Role of VORAXAZE
Hear Dr. Kurt Weiss’s insights on the importance of completing MAP chemotherapy with consideration to surgery with osteosarcoma patients and the role of VORAXAZE in treating methotrexate toxicity.
Clinical Articles
Annals of Emergency Medicine
Expert Consensus Guidelines for Stocking of Antidotes in Hospitals That Provide Emergency Care
Dart RC et al, 2018.
Review recommendations of an expert panel for the stocking of antidotes, including VORAXAZE, in emergency departments.
Blood
Glucarpidase for Treatment of High-Dose Methotrexate Toxicity
Gupta S et al, 2025.
In this real-world evidence study, the authors examined the association between VORAXAZE administration and outcomes in adults with HDMTX-AKI from 28 cancer centers across the United States using a sequential target trial emulation framework.
Cancer
Resumption of High-Dose Methotrexate After Acute Kidney Injury and Glucarpidase Use in Pediatric Oncology Patients
Christensen AM et al, 2012.
The authors report on clinical data and outcomes in pediatric patients who received VORAXAZE after treatment with high-dose methotrexate.
High-Dose Methotrexate-Induced Nephrotoxicity in Patients With Osteosarcoma
Widemann BC et al, 2004.
This review of trials in patients with osteosarcoma and high-dose methotrexate–induced acute kidney injury compares the efficacy of dialysis-based methods and time to renal recovery after supportive treatment with efficacy and renal recovery after treatment with VORAXAZE.
Clinical Journal of Oncology Nursing
High-Dose Methotrexate: Nurse Considerations for Administration and Supportive Care
Roche B et al, 2023.
This article provides an overview of high-dose methotrexate (HDMTX) treatment and nursing considerations, including HDMTX toxicities, components of supportive care, and strategies to manage HDMTX administration and delayed elimination.
Clinical Pharmacology & Therapeutics
MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase
Taylor ZL et al, 2020.
Overview of a web-based clinical decision support tool that helps clinicians monitor whether patients are clearing methotrexate as expected.
Journal of Clinical Oncology
High-Dose Methotrexate in Patients With Lymphoma: Predictors of a Complicated Course
O’Donoghue DF et al, 2022.
A retrospective analysis comprised of 642 adult patients with lymphoma with 2804 cycles of high-dose methotrexate. The incidence of AKI was 19.1%, with acute kidney injury Grade ≥2 making up 21% of cases. Rates of acute kidney injury, ICU admission, and 30-day mortality are associated with elevated 48-hour methotrexate levels. There was a significant increase in median LOS with elevated methotrexate levels (P<.001). Receiver operator characteristic curve analysis for acute kidney injury Grade ≥2 demonstrated a 48-hour methotrexate level threshold of 1.28 μmol/L. Multivariate logistic regression analysis revealed age, male sex, elevated body surface area, higher methotrexate dose, monotherapy, and first cycle as independent factors.
The Oncologist
Consensus Guideline for Use of Glucarpidase in Patients With High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance
Ramsey LB et al, 2018.
Expert Consensus Guidelines for the timely and effective use of VORAXAZE to treat high-dose methotrexate–induced acute kidney injury and delayed methotrexate (MTX) clearance, including supportive care and MTX monitoring before and after treatment.
Preventing and Managing Toxicities of High-Dose Methotrexate
Howard SC et al, 2016.
An overview of the literature regarding high-dose methotrexate therapy and risk for associated toxicities—including comprehensive recommendations for prevention and management of toxicity and treatment guidance for HDMTX-induced acute kidney injury.