Recombinant carboxypeptidase G2 Pregnancy: No available data on use in pregnant women and no animal reproduction studies; given in combination with methotrexate, which can cause embryo-fetal harm — refer to methotrexate prescribing information (§8.1).

Glucarpidase

Brand names: Voraxaze

Glucarpidase is a recombinant enzyme used to rapidly lower toxic methotrexate concentrations in patients with delayed methotrexate clearance and renal impairment.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 50 Units/kg

Route: Intravenous injection over 5 minutes

Frequency: Single dose

US label §2.1: "The recommended dosage of VORAXAZE is 50 Units per kilogram (kg) as a single intravenous injection administered over 5 minutes." Flush the intravenous line before and after administration. Concomitant leucovorin rescue (§2.2): administer leucovorin at least 2 hours before or 2 hours after the glucarpidase dose; for the first 48 hours after the dose give the same leucovorin dose that was given prior to glucarpidase; beyond 48 hours base the leucovorin dose on the measured methotrexate concentration, and continue leucovorin until the methotrexate concentration has been maintained below the leucovorin rescue threshold for a minimum of 3 days. Continue intravenous hydration and urinary alkalinisation as indicated. When measuring methotrexate concentrations after a dose, a chromatographic method is preferred over an immunoassay (DAMPA interferes for up to 48 hours). Paediatric: §8.4 states safety and effectiveness have been established in paediatric patients and that 147 paediatric patients from 1 month to 17 years received glucarpidase with no overall differences in safety versus adults; no separate paediatric mg/kg regimen is stated in this label. Verify paediatric use against a children's formulary. NO UK SPC (eMC) POSOLOGY WAS AVAILABLE IN THIS BUNDLE — dose taken from US labelling; clinician to verify against UK product information.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None (US label §4 states "None")

Side effects

Paraesthesia
Flushing
Nausea and/or vomiting
Hypotension
Headache

Interactions

Leucovorin — glucarpidase can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended
Other folate analogues or folate analogue metabolic inhibitors — concentrations may also be reduced
Methotrexate immunoassays — the metabolite DAMPA interferes with immunoassay measurement of methotrexate (overestimation) for approximately 48 hours; use a chromatographic method

Clinical monograph

How it works

It is a carboxypeptidase that cleaves circulating methotrexate into inactive metabolites, providing an alternative, kidney-independent route of elimination.

Prescribing in practice

Continue folinic acid rescue and hydration, but do not give folinic acid in close proximity to glucarpidase, as the enzyme also degrades folinic acid — refer to the SPC for timing.
Reserve for confirmed toxic methotrexate levels with impaired renal clearance, in consultation with toxicology and the treating oncology team.
Be aware that standard methotrexate immunoassays may overestimate levels after administration owing to interference from the metabolite.

Monitoring

Monitor methotrexate levels, renal function and full blood count, interpreting post-dose methotrexate assays with caution.

Counselling the patient

Explain that this enzyme rapidly clears a chemotherapy drug that the kidneys are struggling to remove.
Tell the team to coordinate the timing of folinic acid around the enzyme dose.
Advise the patient that close blood monitoring will continue afterwards.

Evidence & guidelines

Glucarpidase is used to reduce toxic plasma methotrexate concentrations in patients with delayed clearance and renal dysfunction, alongside continued folinic acid rescue and hydration.

Reference: UKHCDO/UK Children's Cancer SG MTX toxicity guideline; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Pathways