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

    loading  Checking for direct PDF access through Ovid

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.

Related Topics

    loading  Loading Related Articles