Pharmacotherapy. 2021 Mar 2. doi: 10.1002/phar.2516. Online ahead of print.
ABSTRACT
INTRODUCTION: Two case reports describe a possible interaction between levetiracetam and high-dose methotrexate (HDMTX). Only two small retrospective studies have evaluated the interaction, and it remains unclear if concomitant use should be avoided.
METHODS: This single-center, retrospective study evaluated adult lymphoma patients who received HDMTX as a 4-hour infusion with or without concomitant levetiracetam for a difference in incidence of delayed MTX elimination (MTX level > 1µmol/L at 48 hours). Secondary outcomes included incidence of acute kidney injury (AKI) and hospital length of stay (LOS). Generalized estimating equations clustered on patient were used to assess each outcome.
RESULTS: The 430 included patients receiving 1993 doses of HDMTX had a median (IQR) age of 66 (57.5, 72.6) years, 88 (20.5%) received concomitant levetiracetam with at least one dose of MTX, 267 (62.1%) were male, and 397 (92.3%) were Caucasian. HDMTX doses ranged from 1-8 g/m2 . The most common lymphoma diagnoses were systemic diffuse large B-cell lymphoma (DLBCL) (58.5%) and systemic DLBCL with central nervous system (CNS) involvement (32.8%). Rates of delayed elimination with and without levetiracetam were 13.4% and 16.3%, respectively (OR = 0.80, 95% CI 0.47-1.34, p=0.39). AKI occurred in 15.6% and 17.0% of patients with and without concomitant levetiracetam, respectively (OR=0.83, 95% CI 0.52-1.33, p=0.28). The median LOS with and without levetiracetam was 4.2 and 4.1 days, respectively (p=0.039). On multivariable analyses, only age, body surface area, diagnosis of systemic DLBCL with CNS involvement, serum creatinine, hemoglobin, total bilirubin, and dose of HDMTX were associated with delayed elimination.
CONCLUSIONS: HDMTX administered with concomitant levetiracetam was not associated with increased risk for delayed MTX elimination or AKI. These results support that levetiracetam and HDMTX are safe for coadministration.
PMID:33655525 | DOI:10.1002/phar.2516
