Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function

Mariana Fermiano, Jason Bergsbaken, Jill M. Kolesar

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Purpose. The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, administration, and current role in therapy of a recently approved agent for controlling methotrexate toxicity are reviewed. Summary. Glucarpidase is a bacterial enzyme useful in reversing toxicity induced by the widely used antineoplastic agent methotrexate. Glucarpidase gained U.S. marketing approval in 2012 for reducing serum methotrexate concentrations greater than 1 μM/L in patients with delayed methotrexate clearance due to impaired renal function. In clinical trials, glucarpidase has been administered to a total of 3887 patients receiving high-dose methotrexate (i.e., doses of ≥500 mg/m2), including pediatric patients. Patients treated with glucarpidase in addition to standard supportive care (hydration, urinary alkalization, leucovorin rescue, and, in some cases, hemodialysis) had a mean reduction in serum methotrexate levels of greater than 88%, with reductions occurring in a median of 15 minutes; however, up to 4.4% of adult patients and up to 6% of pediatric patients in clinical trial cohorts died despite glucarpidase use, suggesting the agent might not confer a survival advantage over supportive care alone. Glucarpidase is well tolerated; the most common adverse effects are flushing, nausea, vomiting, hypotension, and headache, which are typically grade 1 or 2 in severity and resolve without intervention. Conclusion. Glucarpidase is a well-tolerated and effective treatment for reducing serum methotrexate concentrations greater than 1 μM/ L in patients with impaired renal function. While there are few adverse effects associated with treatment, there may be little or no impact on methotrexate-associated mortality.

Original languageEnglish
Pages (from-to)793-798
Number of pages6
JournalAmerican Journal of Health-System Pharmacy
Volume71
Issue number10
DOIs
StatePublished - May 15 2014

Bibliographical note

Publisher Copyright:
Copyright © 2014 American Society of Health-System Pharmacists Inc. All rights reserved.

ASJC Scopus subject areas

  • Health Policy
  • Pharmacy
  • Pharmacology

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