Glucarpidase information

Glucarpidase
	PDB: 1CG2
Clinical data
Trade names	Voraxaze
AHFS/Drugs.com	Monograph
MedlinePlus	a613009
License data	US DailyMed: Glucarpidase;
Routes of; administration	Intravenous
ATC code	V03AF09 ;
Legal status
Legal status	US: ℞-only; EU: Rx-only;
Identifiers
	IUPAC name Recombinant glutamate carboxypeptidase (carboxypeptidase G2);
CAS Number	9074-87-7;
IUPHAR/BPS	7450;
DrugBank	DB08898;
ChemSpider	none;
UNII	2GFP9BJD79;
KEGG	D10260;
ChEMBL	ChEMBL1863515;
ECHA InfoCard	100.029.968
Chemical and physical data
Formula	C1950H3157N543O599S7
Molar mass	44017.33 g·mol−1

Glucarpidase (Voraxaze) is a medication used 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.^[3] 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.^[4]

Adverse effects include mild and include numbness, tingling, flushing, nausea, vomiting, itching, and headache.^{[medical citation needed]}

^ "Voraxaze- glucarpidase injection, powder, for solution". DailyMed. 28 August 2019. Retrieved 24 April 2022.
^ Cite error: The named reference Voraxaze EPAR was invoked but never defined (see the help page).
^ Green JM (2012). "Glucarpidase to combat toxic levels of methotrexate in patients". Therapeutics and Clinical Risk Management. 8: 403–13. doi:10.2147/TCRM.S30135. PMC 3511185. PMID 23209370.
^ Christensen AM, Pauley JL, Molinelli AR, Panetta JC, Ward DA, Stewart CF, et al. (September 2012). "Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients". Cancer. 118 (17): 4321–30. doi:10.1002/cncr.27378. PMC 3713608. PMID 22252903.

[Voraxaze_FDA_label-1] "Voraxaze- glucarpidase injection, powder, for solution". DailyMed. 28 August 2019. Retrieved 24 April 2022.

[Voraxaze_EPAR-2] Cite error: The named reference Voraxaze EPAR was invoked but never defined (see the help page).

[3] Green JM (2012). "Glucarpidase to combat toxic levels of methotrexate in patients". Therapeutics and Clinical Risk Management. 8: 403–13. doi:10.2147/TCRM.S30135. PMC 3511185. PMID 23209370.

[4] Christensen AM, Pauley JL, Molinelli AR, Panetta JC, Ward DA, Stewart CF, et al. (September 2012). "Resumption of high-dose methotrexate after acute kidney injury and glucarpidase use in pediatric oncology patients". Cancer. 118 (17): 4321–30. doi:10.1002/cncr.27378. PMC 3713608. PMID 22252903.