Baseline studies indicated; see Monitor.
50 units/kg as a single intravenous injection over 5 minutes.
See Usual Dose.
No dose adjustment is recommended in patients with renal impairment. ■ Has not been studied in patients with hepatic impairment.
Available in a vial containing 1,000 units of lyophilized powder. Reconstitute with 1 mL of NS to provide a solution containing 1,000 units/vial. Roll and tilt vial gently to mix. Do not shake. Solution should be clear and colorless. Withdraw calculated dose from vial for administration as an IV injection.
Refrigerate unopened vials at 2° to 8° C (36° to 46° F). Do not freeze. Do not use beyond expiration date on vial. Use reconstituted solution immediately or store under refrigeration for up to 4 hours. Discard any unused product.
Administer as an injection evenly distributed over 5 minutes. Flush IV line before and after administration.
A carboxypeptidase enzyme produced by recombinant DNA technology. Hydrolyzes the carboxyl-terminal glutamate residue from folic acid and classic antifolates such as methotrexate. Converts methotrexate to its inactive metabolite, 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate. Glucarpidase provides an alternate nonrenal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment. The desired end point of therapy is a rapid and sustained clinically important reduction (RSCIR) in methotrexate concentration, which is defined as attaining a plasma methotrexate concentration less than or equal to 1 μmol/L at 15 minutes and sustaining it for up to 8 days after administration of glucarpidase. The likelihood of attaining a RSCIR correlates with the pre-glucarpidase methotrexate concentration. However, even patients with methotrexate concentrations greater than 50 μmol/L were able to achieve greater than 95% reduction in methotrexate concentrations for up to 8 days following glucarpidase administration. Glucarpidase distribution is restricted to the plasma volume. Mean elimination half-life is 5.6 hours.
Reduce toxic plasma methotrexate concentrations (greater than 1 μmol/L) in adult and pediatric patients with delayed methotrexate clearance (plasma methotrexate concentrations greater than 2 standard deviations of the mean methotrexate excretion curve specific for the dose of methotrexate administered) due to impaired renal function.
Not recommended for use in patients who exhibit the expected clearance and expected plasma methotrexate concentration. Reducing plasma methotrexate concentration in these patients may result in subtherapeutic exposure to methotrexate.
Serious hypersensitivity reactions, including anaphylaxis, have been reported. ■ Efficacy of a second dose of glucarpidase in patients with markedly elevated pre-glucarpidase methotrexate concentrations was not demonstrated in studies. ■ Continue hydration, alkalinization of the urine, and leucovorin rescue as indicated; see Monitor and methotrexate and leucovorin monographs. ■ A protein substance, it has the potential to produce immunogenicity. Anti-glucarpidase antibodies have been detected in a small number of patients treated with glucarpidase.
Obtain baseline and periodic renal function tests (e.g., SCr and BUN). ■ Watch for early S/S of hypersensitivity or infusion reactions (e.g., chills, dyspnea, fever, flushing, headache, hives, itching, numbness, rash, throat tightness). ■ Monitor methotrexate concentrations. During the first 48 hours after glucarpidase administration, methotrexate concentrations can be reliably measured only by a chromatographic method. During this period, DAMPA (the inactive metabolite of methotrexate) interferes with the measurement of methotrexate concentration using immunoassays. ■ When administering glucarpidase concomitantly with leucovorin, administer leucovorin at least 2 hours before or 2 hours after the glucarpidase dose; see Drug/Lab Interactions. ■ For 48 hours after glucarpidase administration, determine the leucovorin dose based on the patient’s pre-glucarpidase methotrexate concentration (i.e., administer the same leucovorin dose given before the glucarpidase dose). Beyond 48 hours, administer leucovorin based on the measured methotrexate concentration. Do not discontinue leucovorin based on the determination of a single methotrexate concentration below the leucovorin rescue threshold. Continue therapy with leucovorin until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days; see leucovorin monograph. Monitor for S/S of potential methotrexate toxicity (e.g., abdominal distress, chills, dizziness, fever, leukopenia, malaise, nausea, stomatitis, undue fatigue). ■ Continue IV hydration and urinary alkalinization as indicated.
Promptly report any S/S of a hypersensitivity reaction or an infusion reaction (e.g., chills, feeling hot, fever, flushing, headache, hives, itching, numbness, rash, throat tightness or breathing problems, tingling). ■ Continued monitoring of methotrexate levels and renal status is imperative.
Safety for use during pregnancy and breast-feeding not established. Administered in combination with methotrexate, which can cause embryo-fetal harm. See methotrexate monograph. ■ Effectiveness in pediatric patients has been established in clinical studies. No overall differences in safety were observed between pediatric patients (age 1 month to 17 years of age) and adult patients.
No overall differences in safety or effectiveness were observed between elderly patients and younger patients.
Leucovorin is a substrate for glucarpidase. Do not administer leucovorin within 2 hours before or after a dose of glucarpidase. Glucarpidase can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended. ■ Other potential exogenous substrates of glucarpidase include reduced folates and folate antimetabolites, other folate analogs or folate analog metabolic inhibitors.■ During the first 48 hours after glucarpidase administration, methotrexate concentrations can be reliably measured only by a chromatographic method. During this period, DAMPA (the inactive metabolite of methotrexate) interferes with the measurement of methotrexate concentration using immunoassays.
The most commonly reported side effects included flushing, headache, hypotension, nausea, paraesthesia, and vomiting. Other reported adverse reactions included blurred vision, diarrhea, hypersensitivity reactions (including anaphylaxis), hypertension, rash, throat irritation or tightness, and tremor.
Notify the physician of any side effects. Discontinue the drug if indicated. Treat hypersensitivity reactions as indicated (airway, oxygen, IV fluids, antihistamines [e.g., diphenhydramine], corticosteroids [e.g., hydrocortisone sodium succinate], epinephrine, pressor amines [e.g., dopamine]) and resuscitate as necessary.