Glucarpidase

Glucarpidase (Voraxaze) is an FDA-approved intravenous drug for the treatment of elevated levels of methotrexate (defined as 1 micromol/L) during treatment of cancer patients who have impaired kidney function (and thus cannot reduce the drug to safe levels sufficiently after the drug has been given). 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 (within two hours of one another).

Glucarpidase, a recombinant form of the bacterial enzyme carboxypeptidase G2 converts methotrexate into glutamate and 2,4-diamino-N(10)-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.

So far adverse effects that have been reported have been mild and include numbness, tingling, flushing, nausea, vomiting, itching, and headache.