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

PURPOSEThe pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, administration, and current role in therapy of a recently approved agent for controlling methotrexate toxicity are reviewed. SUMMARYGlucarpidase is a bacterial enzyme useful in reversing toxicity induced by the widely used...

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Bibliographic Details
Published in:	American journal of health-system pharmacy Vol. 71; no. 10; pp. 793 - 798
Main Authors:	FERMIANO, MARIANA, BERGSBAKEN, JASON, KOLESAR, JILL M
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Copyright American Society of Health-System Pharmacists, Inc. All rights reserved 15-05-2014 American Society of Health Pharmacists Oxford University Press
Subjects:	Antimetabolites, Antineoplastic - blood Biological and medical sciences Drug therapy Drug toxicity and drugs side effects treatment Drugs gamma-Glutamyl Hydrolase - therapeutic use Health aspects Humans Kidney diseases Medical sciences Methotrexate Methotrexate - blood Pharmacology. Drug treatments Renal Insufficiency - metabolism Toxicity: urogenital system United States Antifolate Antineoplastic agent Human Clinical management Renal function Treatment Antimetabolic Enzyme Toxicity Glucarpidase Methotrexate
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Summary:	PURPOSEThe pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, administration, and current role in therapy of a recently approved agent for controlling methotrexate toxicity are reviewed. SUMMARYGlucarpidase 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/m), 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. CONCLUSIONGlucarpidase 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.
ISSN:	1079-2082 1535-2900
DOI:	10.2146/ajhp130483