TY - JOUR
T1 - Glucarpidase for the management of elevated methotrexate levels in patients with impaired renal function
AU - Fermiano, Mariana
AU - Bergsbaken, Jason
AU - Kolesar, Jill M.
PY - 2014/5/15
Y1 - 2014/5/15
N2 - 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.
AB - 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.
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U2 - 10.2146/ajhp130483
DO - 10.2146/ajhp130483
M3 - Review article
C2 - 24780487
AN - SCOPUS:84907210572
VL - 71
SP - 793
EP - 798
IS - 10
ER -