Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Aug;46(4):918-926.
doi: 10.1111/jcpt.13464. Epub 2021 Jun 19.

Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases

David Brandariz-Nuñez  1 , Marcelo Correas-Sanahuja  2 , Sara Maya-Gallego  3 , Isabel Martín Herranz  1
Affiliations

Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases

David Brandariz-Nuñez et al. J Clin Pharm Ther. 2021 Aug.

Abstract

What is known and objective: Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions.

Methods: A systematic review of cases was carried out following the guidelines established by "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA). The research was carried out using the PubMed-Medline and Embase databases, between July 1984 and March 2021.

Results and discussion: A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5-88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end-stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2-28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2-180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days.

What is new and conclusion: The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis.

Keywords: acyclovir; dialysis; neurotoxicity; renal failure; valacyclovir.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Centers for Disease Control and Prevention. Shingles (herpes zoster): clinical overview, 2020. https://www.cdc.gov/shingles/hcp/clinical-overview.html
    1. Rogers HJ, Fowle ASE. The clinical pharmacology of acyclovir. J Clin Hosp Pharm. 1983;8:89-102.
    1. Blum RM, Liao SH, de Miranda P. Overview of acyclovir pharmacokinetic disposition in adults and children. Am J Med. 1982;73(1A):186-192.
    1. Beutner KR. Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antiviral Res. 1995;28(4):281-290.
    1. Patel R. Valaciclovir: development, clinical utility and potential. Expert Opin Investig Drugs. 1997;6(2):173-189.

Publication types

LinkOut - more resources