Valacyclovir Induced Neurotoxicity, with Therapeutic Drug Monitoring, in a Hospital-Based Setting in the Netherlands.

Background: Valacyclovir-induced neurotoxicity is a rare side effect. The aim of this study was to perform a retrospective analysis of patients with valacyclovir-induced neurotoxicity and establish valacyclovir plasma concentrations in a tertiary hospital between January 2018 and November 2022.

Case descriptions: In total 208 patients were identified with measured acyclovir concentrations, and the electronic health records of these patients were analysed. Based on the in- and exclusion criteria, 4 patents were identified in whom high plasma concentrations were linked to neurotoxicity. The first patient experienced balance and coordination problems, visual hallucinations, speaking difficulties and headaches. The second patient experienced a progressive decline of consciousness, resulting in coma. The third patient also experienced reduced consciousness and was found unconscious on the floor during the night. The fourth patient experienced vertigo after administration of acyclovir.

Conclusion: Based on this study, neurotoxicity appears to be an underreported adverse effect of valacyclovir therapy in a hospital setting. This side effect may have a high impact on individuals as well as on the duration of hospitalization. In order to exclude valacyclovir as the cause, clinicians should consider requesting an acyclovir plasma concentration as standard hospital-based intervention whenever a patient experiences neurotoxic symptoms. Moreover, pharmacists and clinicians should be made better aware of the interaction between valacyclovir and cyclosporine and/or mycophenolic acid, in particular in elderly patients with impaired kidney function.

Learning points: Valaciclovir-induced neurotoxicity diagnosis is underreported.Accessible and frequent therapeutic drug monitoring (TDM) of valacyclovir is recommended.Interactions between valaciclovir and ciclosporin and/or mycophenolic acid, in particular in elderly patients with impaired kidney function, need a follow-up during hospitalization.