Successful Treatment of Delayed Methotrexate Clearance Using Glucarpidase Dosed on Ideal Body Weight in Obese...

Delayed methotrexate (MTX) elimination after treatment with high-dose (HD) MTX may result in life-threatening toxicities as well as acute kidney injury (AKI). Treatment includes administration of glucarpidase, an enzyme that rapidly inactivates MTX. Dosing of glucarpidase is based on body weight; however, recommendations for dosage adjustments in obese patients are lacking. We describe three obese adult patients (body mass index [BMI] range 31-43 kg/m² ) who received HD-MTX following all precautions for its treatment. Although peak MTX concentrations were within the expected range (308-368 µmol/L), MTX concentrations after 24 hours or later were markedly increased (97, 52, and 19 µmol/L, respectively). Two patients experienced AKI. After a single intravenous dose of glucarpidase 4000 units (50 units/kg on the basis of ideal body weight [IBW]) was administered to each patient 38, 46, and 60 hours, respectively, after the start of MTX, MTX concentrations dropped quickly to 1.37, 0.07, and 0.03 µmol/L, respectively, and further decreased steadily. Over time, clinical status and renal function improved in all patients. Glucarpidase is a highly hydrophilic molecule with a volume of distribution of 3.6 L, representing the intravascular volume of an adult. Therefore, we used IBW for glucarpidase dose calculations, allowing us to reduce the dose that would have been determined by using total body weight. This approach resulted in a rapid decrease of MTX serum concentrations and may reduce treatment costs of this highly expensive drug.