Drug information of Glucarpidase

Glucarpidase is a recombinant enzyme which rapidly hydrolyzes the carboxyl-terminal glutamate residue from extracellular methotrexate into inactive metabolites (DAMPA and glutamate), resulting in a rapid reduction of methotrexate concentrations independent of renal function

Onset of Action:Methotrexate toxicity: Reduces methotrexate concentrations by ≥97% within 15 minutes of IV administration

Duration of Action:Methotrexate toxicity: Maintains a >95% reduction of methotrexate concentrations for up to 8 day

Peak Plasma Concentration: 3.3 mcg/mL

Vd: 3.6 L

Half-life (based on serum activity levels): 5.6 hr; 8.2 hr (renal impairment)

Half-life (based on serum total concentrations): 9 hr

Systemic clearance: 7.5 mL/min

Methotrexate Toxicity

50 units/kg as a single IV injection over 5 minutes

There are no contraindications listed in the manufacturer's labeling.

Paresthesias

Flushing

Nausea/vomiting

Headache

Hypotension

Blurred vision

Diarrhea

Hypersensitivity

Hypertension

Rash

Throat irritation/throat tightness

Tremor

Antibody formation

Serious hypersensitivity reactions

folic acid

L-methylfolate

leucovorin

pemetrexed

pentamidine

pralatrexate

sulfamethoxazole

trimethoprim

Serious allergic reactions (occurred in <1% of patients)

17% (n=16) of patients developed anti-glucarpidase antibodies

Leucovorin is a substrate for glucarpidase.Do not administer leucovorin within 2 hr before or after glucarpidase

Serious allergic reactions (occurred in <1% of patients)

17%  of patients developed anti-glucarpidase antibodies

Leucovorin is a substrate for glucarpidase.Do not administer leucovorin within 2 hr before or after glucarpidase

Methotrexate concentrations within 48 hours following administration of glucarpidase can only be reliably measured by a chromatographic method

DAMPA is an inactive metabolite of methotrexate resulting from treatment with glucarpidase that interferes with the measurement of methotrexate concentration using immunoassays

Due to the long half-life of DAMPA (~9 hours), measurement of methotrexate using immunoassays is unreliable for samples collected within 48 hours following glucarpidase administration

No dose adjustment is recommended for the continuing leucovorin regimen

For the first 48 hours after glucarpidase, administer the same leucovorin dose as given prior to glucarpidase

Beyond 48 hours after glucarpidase, administer leucovorin based on the measured methotrexate concentration

Continue hydration and alkalinization of the urine as indicated

There are no available data on use in pregnant women or animal reproduction studies to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes