General Information

Voraxaze (glucarpidase) contains a recombinant enzyme that rapidly lowers blood levels of methotrexate, reducing its concentration to below the threshold for serious toxicity. Voraxaze converts methotrexate to its inactive metabolites DAMPA and glutamate. DAMPA and glutamate are metabolized by the liver, providing an alternative route of methotrexate elimination to renal clearance during high-dose methotrexate treatment.

Voraxaze is specifically indicated for the treatment of toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function.

Mechanism of Action

Voraxaze (glucarpidase) is a recombinant bacterial enzyme that hydrolyzes the carboxyl-terminal glutamate residue from folic acid and classical antifolates such as methotrexate. Voraxaze converts methotrexate to its inactive metabolites 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate. DAMPA and glutamate are metabolized by the liver, providing an alternative route of methotrexate elimination to renal clearance during high-dose methotrexate treatment.

Side Effects

Adverse events associated with the use of Voraxaze may include, but are not limited to, the following:

• Paraesthesia
• Flushing
• Nausea and/or vomiting
• Hypotension
• Headache

Dosing/Administration

Voraxaze is supplied as a solution for intravenous administration. The recommended dose is a single intravenous injection of 50 units per kg. as a bolus injection over five minutes.

Clinical Trial Results

FDA Approval
The FDA approval of Voraxaze was based on an efficacy and safety study.
 

Efficacy Study
A single clinical study enrolled 22 subjects. All subjects received Voraxaze treatment. The treatment was considered effective if the methotrexate level fell below a critical level within 15 minutes and stayed below the critical level for eight days. Ten of the 22 subjects achieved this standard. Voraxaze eliminated 95 percent of the methotrexate in all subjects, regardless of whether they reached the efficacy end point.
 

Safety Study
A separate clinical study evaluated the safety of Voraxaze in 290 subjects experiencing problems clearing methotrexate from their blood. The most common side effects observed in greater than 1 percent of subjects in the clinical study were low blood pressure (hypotension), headache, nausea, vomiting, flushing and abnormal sensation (paraesthesia).