Clinical implications of Brivaracetam Cross-Reactivity with levetiracetam immunoassay

Brivaracetam (BRV) and levetiracetam (LEV) are structurally similar, causing LEV immunoassays (IA) to cross-react with BRV, the real-world clinical implications of which have not been previously characterized. We analyzed 36 patients with 54 serum level measurements, including levels drawn when patients were not receiving the corresponding medication or simultaneous LEV/BRV levels when both ASM were co-administered. LEV levels were measured by IA; BRV levels by LC-MS/MS. Among 14 paired measurements in BRV-only patients, the median cross-reactivity ratio was 14.7. False-positive LEV levels at therapeutic BRV concentrations fell within or above the LEV therapeutic range, making the artifact clinically indistinguishable from true LEV exposure when co-prescribed with BRV. Erroneous orders accounted for 28/54 observations, most commonly from stale standing orders persisting after LEV-to-BRV conversion. Cross-reactivity influenced clinical management in 7/54 observations. Despite this cross-reactivity being well established in literature, our case series demonstrated that this knowledge might not have adequately translated to clinical practice, resulting in misinterpretation of serum levels impacting clinical decisions. Given the complexity of modern healthcare workflows, reliance on individual clinician awareness is insufficient; electronic medical record systems should explore implementing medication-laboratory linkage alerts. Lastly, LEV LC-MS/MS should be used when both anti-seizure medications (ASM) are co-prescribed.