Voraxaze ® (glucarpidase) is indicated for the treatment of toxic plasma methotrexate concentrations ( 1 μmol/L) in patients with delayed methotrexate clearance due to impaired renal function VORAXAZE (glucarpidase) is indicated for the treatment of toxic plasma methotrexate concentrations ( 1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function. Glucarpidase is indicated for the treatment of toxic plasma methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function. Glucarpidase is not indicated for use in patients who exhibit the expected clearance of methotrexate or those with normal or mildly impaired renal function because of the potential risk of subtherapeutic exposure to methotrexate May consider adding glucarpidase to leucovorin or levoleucovorin rescue therapy to treat toxic plasma methotrexate concentrations ( 0.454 mcg/mL or 1 µM) in patients with delayed methotrexate clearance due to renal impairment. 266 If glucarpidase is used, do not administer leucovorin or levoleucovorin within 2 hours before or after a dose of glucarpidase. 266 Potentially toxic: after 24 hours: 5.00 μmol/L, after 48 hours: 0.50 μmol/L, after 72 hours: 0.05 μmol/L Additional Information Methotrexate is an antimetabolite that combines with dihydrofolate reductase and therefore interferes with the synthesis of tetrahydrofolic acid necessary for DNA synthesis. Furthermore, the area under the plasma concentration-time curve, a frequently used metric, does not correlate with toxic response. This can be seen in Figure 5 (Zaharko, 1975). The steep curve shows the MTX plasma concentration following the 350-mg/kg bolus dose, while the flat curve shows the concentration following the 3-mg/kg 96-h infusion. Abstract. To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drug's clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. In January 2012, glucarpidase (Voraxaze ®) received approval from the US Food and Drug Administration for intravenous treatment of toxic plasma methotrexate concentrations due to impaired renal clearance. Voraxaze (glucarpidase) is an antidote indicated for the treatment of plasma methotrexate (MTX) toxicity in patients with delayed elimination of methotrexate due to kidney dysfunction. A case of methotrexate-induced acute renal failure successfully treated with plasma perfusion and sequential hemodialysis. Nephron 1995; 71:233. Nephron 1995; 71:233. Jambou P, Levraut J, Favier C, et al. Removal of methotrexate by continuous venovenous hemodiafiltration.