Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + INTRODUCTION Download Section PDF Listen +++ ++ Pharmacology. Glucarpidase (carboxypeptidase G2, CPDG2) is a recombinant form of carboxypeptidase G2, which rapidly hydrolyzes the carboxyl-terminal glutamate residue of folate and folate analogues such as methotrexate. Methotrexate is inactivated producing the nontoxic metabolites 4-deoxy- 4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, resulting in a ≥97% reduction of methotrexate levels within 15 minutes, independent of renal clearance. Because of its large molecular size, it distributes primarily in the intravascular space and does not cross the blood-brain barrier or cell membranes, and it does not inactivate methotrexate in the gut lumen. Its half-life ranges from 5.6 hours to 8.2 hours (renal impairment). Indications Glucarpidase is indicated for the adjunctive treatment of toxic plasma methotrexate (see Methotrexate) concentrations in the setting of impaired renal clearance or persistent toxic levels. It should be used in conjunction with leucovorin rescue (with staggered dosing; see V. B. below) and supportive care (IV hydration and urinary alkalinization). Unlabeled uses include intrathecal administration for inadvertent intrathecal methotrexate overdose. Contraindications. None are listed by the manufacturer. Adverse effects Immunologic: Antibody development (21%) is of uncertain clinical importance but may impact effectiveness of repeat dosing (see dosing and method of administration below). Allergic: Severe allergic reactions have been reported in postmarketing surveillance. Typically, less severe reactions occur including a burning sensation, flushing, nausea, vomiting, headache, and hypotension. Use in pregnancy. FDA Category C (see Table III–1). There are no well-controlled studies in pregnant animal or human subjects with this drug. Drug or laboratory interactions The inactive hydrolysis product of methotrexate, DAMPA, may interfere with methotrexate immunoassays, resulting in overestimation of methotrexate concentrations in samples collected within 48 hours of glucarpidase administration. Chromatographic methotrexate assays are accurate during this time frame. Leucovorin is also a substrate for glucarpidase, and the manufacturer advises against administration of leucovorin within 2 hours before or after administration of glucarpidase. Dosage and method of administration (adults and children) Toxic methotrexate levels. Give 50 units/kg infused by IV bolus over 5 minutes. Reconstitute powder for injection by adding 1 mL of sterile 0.9% sodium chloride for injection. A second dose may be considered 24–48 hours later if there is evidence of persistent toxic methotrexate levels. However, administration of a second dose has not been shown to provide benefit. Acute intrathecal overdose. Give 2,000 units, reconstituted in sterile 0.9% sodium chloride, as soon as possible after methotrexate overdose, administered over 5 minutes via ventriculostomy, lumbar route, ventriculostomy, or Ommaya reservoir. Formulations Parenteral and intrathecal. Lyophilized powder 1,000 units per vial, stable in normal saline. Suggested minimum stocking levels: Glucarpidase is distributed as Voraxaze® through ASD Healthcare; procurement information is available at 1-855-7-VORAXAZE (1-855-786-7292). Certain pharmacy wholesalers in the United States are capable of shipping glucarpidase for overnight delivery; additional information at http://www.btgplc.com/products/specialty-pharmaceuticals/voraxaze.