Journal article
Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function
American journal of health-system pharmacy, Vol.71(10), pp.793-798
05/15/2014
DOI: 10.2146/ajhp130483
PMID: 24780487
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 mu M/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(2)), 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 M/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.
Details
- Title: Subtitle
- Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function
- Creators
- Mariana Fermiano - Universidade Estadual de Campinas (UNICAMP)Jason Bergsbaken - UW Health University HospitalJill Kolesar - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- American journal of health-system pharmacy, Vol.71(10), pp.793-798
- Publisher
- Amer Soc Health-System Pharmacists
- DOI
- 10.2146/ajhp130483
- PMID
- 24780487
- ISSN
- 1079-2082
- eISSN
- 1535-2900
- Number of pages
- 6
- Grant note
- CAPES Foundation of the Ministry of Education of Brazil; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Language
- English
- Date published
- 05/15/2014
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984695801202771
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