Glucarpidase

VORAXAZE is indicated to reduce toxic plasma methotrexate concentration (greater than 1 micromole per liter) 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. Limitations of Use: VORAXAZE is 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.

Glucarpidase is a recombinant bacterial enzyme that hydrolyzes the carboxyl- terminal glutamate residue from folic acid and classical antifolates such as methotrexate. Glucarpidase converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N 10 - methylpteroic acid (DAMPA) and glutamate. VORAXAZE provides an alternate non-renal pathway for methotrexate elimination in patients with renal dysfunction during high-dose methotrexate treatment.

The recommended dosage of VORAXAZE is 50 Units per kilogram as a single intravenous injection over 5 minutes. For the first 48 hours after the dose of VORAXAZE, administer the same leucovorin dose given prior to VORAXAZE. Administer leucovorin at least 2 hours before or 2 hours after the dose of VORAXAZE. Beyond 48 hours after the dose of VORAXAZE, administer leucovorin based on the measured methotrexate concentration. Continue leucovorin until the methotrexate concentration has been maintained below the leucovorin treatment threshold for a minimum of 3 days.

None. None.

Serious Hypersensitivity Reactions: Serious hypersensitivity reactions occurred. Monitoring Methotrexate Concentration: Measure methotrexate concentrations within 48 hours following VORAXAZE administration using a chromatographic method, immunoassays are unreliable for samples collected within 48 hours following VORAXAZE administration.

The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Hypersensitivity Reactions [Warnings and Precautions ]. The most common related adverse events (>1%) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache.

Effects of VORAXAZE on Leucovorin VORAXAZE can decrease leucovorin concentration, which may decrease the effect of leucovorin rescue unless leucovorin is dosed as recommended. VORAXAZE may also reduce the concentrations other folate analogs or folate analog metabolic inhibitors.

Store VORAXAZE refrigerated at 36°F to 46°F (2°C to 8°C). Do not freeze.