Glucarpidase
Glucarpidase is a medication used for the treatment of elevated levels of methotrexate during treatment of cancer patients who have impaired kidney function. Glucarpidase is an enzyme that inactivates methotrexate rapidly after injection. Because this agent reduces systemic levels of methotrexate and could therefore interfere with efficacy, it is not recommended for use in patients with normal or only slightly impaired kidney function or in whom serum levels are normal. The main antidote for methotrexate overdoses prior to the approval of this drug were high doses of folinic acid. However, this agent was not always sufficient at preventing kidney failure due to methotrexate. Glucarpidase also degrades folinic acid so the two should not be used together.
Glucarpidase, a recombinant form of the bacterial enzyme carboxypeptidase G2 converts methotrexate into glutamate and 2,4-diamino-N-methylpteroic acid. These are generally much less toxic and are excreted largely by the liver. One case series in children has found that high-dose methotrexate therapy can be resumed after an instance of methotrexate-induced acute kidney injury successfully treated with glucarpidase.
Adverse effects include mild and include numbness, tingling, flushing, nausea, vomiting, itching, and headache.