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Megludase is a recombinant carboxypeptidase G2 enzyme produced in *Escherichia coli*. It is specifically indicated for the detoxification of methotrexate in patients who exhibit toxic blood concentrations of the drug due to delayed clearance, typically resulting from methotrexate-induced renal impairment. Megludase works by rapidly hydrolyzing the terminal glutamate residue of methotrexate, converting it into the inactive metabolites 4-amino-4-deoxy-N10-methylpteroic acid (DAMPA) and glutamate. This provides an alternative, non-renal pathway for methotrexate elimination, thereby reducing systemic toxicity. Developed and marketed in Japan by OHARA Pharmaceutical, it is used as an adjunct to standard leucovorin rescue therapy when methotrexate excretion is significantly delayed.
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