DOI: 10.12890/2024_004479
Valacyclovir induced neurotoxicity, with therapeutic drug monitoring, in a hospital-based setting in the Netherlands
Authors
j.f.h.eijsink@isala.nl
Keywords
Valacyclovir-neurotoxicity, interactions, therapeutic drug monitoringAbstract
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.
References
- Morris DJ. Adverse effects and drug interactions of clinical importance with antiviral drugs. Drug Saf 1994;10:281-291.
- Hannemann J, Wunderle W, Yousif T, Krüger S, Baumann K. Toxic effect of concomitant administration of cyclosporin A and acyclovir on renal function and morphology in rats. Arch Toxicol 1997;71:556-562.
- Lam NN, Weir MA, Yao Z, Blake PG, Beyea MM, Gomes T, et al. Risk of acute kidney injury from oral acyclovir: a population-based study. Am J Kidney Dis 2013;61:723-729.
- Helldén A, Lycke J, Vander T, Svensson JO, Odar-Cederlöf I, Ståhle L. The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment. J Antimicrob Chemother 2006;57:945-949.
- von Euler M, Axelsson G, Helldén A. Differential diagnosis of central nervous system involvement in a patient treated with acyclovir. Ther Drug Monit 2013;35:417-419.
- Kacirova I, Urinovska R, Sagan J. Therapeutic monitoring of serum concentrations of acyclovir and its metabolite 9-(carboxymethoxymethyl) guanine in routine clinical practice. Biomed Pharmacother 2022;156:113852.
- Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245.
- Gimenez F, Foeillet E, Bourdon O, Weller S, Garret C, Bidault R, et al. Evaluation of pharmacokinetic interactions after oral administration of mycophenolate mofetil and valaciclovir or aciclovir to healthy subjects. Clin Pharmacokinet 2004;43:685-692.
