Glucarpidase

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Glucarpidase
Glutamate carboxypeptidase 1CG2.png
PDB: 1CG2​
Clinical data
Trade namesVoraxaze
AHFS/Drugs.comMonograph
MedlinePlusa613009
Routes of
administration		IV
ATC code
  • V03AF09
Legal status
Legal status
Identifiers
  • Recombinant glutamate carboxypeptidase (carboxypeptidase G2)
CAS Number
IUPHAR/BPS
ChemSpider
  • none
UNII
KEGG
ECHA InfoCard100.029.968 Edit this at Wikidata
Chemical and physical data
FormulaC1950H3157N543O599S7 (monomer)
Molar mass44017.33 g·mol−1

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.[1] 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.[2]

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

Society and culture[]

Legal status[]

In November 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Voraxaze, intended to reduce toxic plasma methotrexate concentration.[3] The applicant for this medicinal product is SERB SAS.[3]

References[]

  1. ^ 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.
  2. ^ 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.
  3. ^ a b "Voraxaze: Pending EC decision". European Medicines Agency. 11 November 2021. Retrieved 13 November 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links[]

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