Effect of Levetiracetam on Time to High-Dose Methotrexate Clearance in Patients With Hematologic Malignancies

High-dose methotrexate (HDMTX) is a commonly used treatment for hematologic malignancies involving the central nervous system. Two case reports described possible delayed methotrexate clearance in patients receiving concurrent levetiracetam, while a retrospective cohort study did not find this association. The objective of this single-center, retrospective case-control study of 121 patients who received their first cycle of HDMTX was to investigate the association between HDMTX clearance time and concomitant levetiracetam use. The most common diagnosis was primary central nervous system lymphoma (47.9%). The mean HDMTX dose was 4601 mg/m² (standard deviation [SD], 2052.6 mg/m² ). Concurrent levetiracetam was administered in 30 of 121 patients (24.8%), with a mean total daily levetiracetam dose of 1434.4 mg (SD, 622.9 mg; range, 900-3000 mg). Baseline characteristics were similar between patients who received concomitant levetiracetam and those who did not. The mean time to methotrexate clearance was 82.5 hours (SD, 51.2; 95% confidence interval, 69.4-95.7) in the concomitant levetiracetam group and 72.4 hours (SD, 31.2; 95% confidence interval, 61.7-83.0) in the nonlevetiracetam group, which was not significantly different (P > .05), even in the subgroup receiving methotrexate doses >3500 mg/m² . Grade 3 or higher toxicity occurred in 33.3% of the concomitant levetiracetam group and in 34.1% of nonconcomitant levetiracetam patients. This study, which, to our knowledge, is the first examining levetiracetam effect on only the first dose of HDMTX, supports the larger retrospective study finding no significant effect of levetiracetam on HDMTX clearance time, and suggests that administering concomitant levetiracetam does not affect HDMTX toxicity.