Varicella-zoster virus meningitis during amenamevir therapy with measured cerebrospinal fluid drug concentration: A...

Varicella-zoster virus (VZV) meningitis has been reported during treatment with amenamevir (AMNV). Although case reports have raised concerns about its ability to prevent central nervous system (CNS) complications, cerebrospinal fluid (CSF) penetration has not been evaluated. We report the first case of VZV meningitis with measured CSF AMNV concentration. An 80-year-old man developed altered consciousness and dysarthria on day 7 of AMNV therapy for thoracic herpes zoster. The CSF AMNV concentration on admission was 0.086 µmol/L (41.3 ng/mL), measured 20-24 h after the last dose, within the reported in vitro half-maximal effective concentration (EC₅₀) range for VZV (0.055-0.10 µmol/L) in Japan; however, the clinical relevance of this comparison remains uncertain. The patient's condition improved rapidly after initiation of acyclovir therapy. This case provides the first direct evidence that AMNV reaches the CSF. However, whether CSF exposure is sufficient to prevent CNS complications or attenuate disease severity remains unclear.