Elderly patients are at higher risk of developing valacyclovir-related neurotoxicity due to underlying hepatic or renal impairment. For instance, in one study, 83 percent of cases of valacyclovir neurotoxicity had concomitant acute renal dysfunction.⁴ The treatment for valacyclovir toxicity is discontinuation of the medication and in patients with severe renal dysfunction and persistent symptoms, potentially dialysis.⁵

This case highlights an important clinical pearl for clinicians prescribing valacyclovir for shingles. According to the CDC, 30 percent of the population at some point during their lifetime will be diagnosed with shingles, and the emergency department can serve as the first point of contact for these patients.⁵ In most cases, shingles can be treated on an outpatient basis, but special consideration should be taken for elderly patients who present to the ED for evaluation of shingles. It is imperative to obtain baseline kidney function tests or review prior renal function tests, as the dosage of valacyclovir is renally adjusted; this can potentially mitigate neurotoxicity along with morbidity and mortality.

Additionally, this case highlights the challenges seen in patients who present with altered mental status. An often overlooked differential diagnosis for altered mental status in elderly patients is drug-induced encephalopathy. With increasing life expectancy and medical advances, elderly patients often have exhaustive medication lists, raising the concern for polypharmacy. One study demonstrated that 65.9 percent of elderly patients had polypharmacy, and 38 percent of elderly patients had major polypharmacy, defined as taking four or more medications concurrently.⁶ Additionally, obtaining historical data regarding medication changes and compliance may prove to be a challenge for the emergency physician, therefore making it challenging to identify polypharmacy as the etiology of a patient’s altered mental status. It is imperative to utilize pharmacy records and obtain external historical data from rehabilitation or nursing facilities, family members, and caregivers to help elucidate recent medication changes that could be contributing to a patient’s altered mental status.

Dr. Pandya is a third-year emergency medicine resident at Baystate Medical Center in

Springfield, MA.

Dr. Kelly is an emergency medicine attending physician and regional EMS medical director/division chief of prehospital and disaster medicine at Baystate Health in Springfield, MA.

References

1. Tyring S, Douglas J, Corey L. A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immuno-competent patients with recurrent genital herpes infections. Archives of Dermatology. 1998;134(2):185.
2. Brandariz-Nuñez D, Correas-Sanahuja M, Maya-Gallego S, et al. Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases. Journal of Clinical Pharmacy and Therapeutics. 2021;46(4):918-926.
3. Lam N, Weir M, Yao Z, et al. Risk of acute kidney injury from oral acyclovir: A population-based study. Am J Kidney Dis. 2013;61(5):723-9.
4. Murakami T, Akimoto T, Okada M, et al. Valacyclovir neurotoxicity and nephrotoxicity in an elderly patient complicated by hyponatremia. Drug Target Insights. 2018;12(1):1-5.
5. Shingles surveillance, trends, deaths. Centers for Disease Control website. https://www.cdc.gov/shingles/surveillance.html. Published April 12, 2021. Accessed January 8, 2024.
6. Young EH, Pan S, Yap AG, et al. Polypharmacy prevalence in older adults seen in United States physician offices from 2009 to 2016. PLOS ONE.2021;16(8):e0255642.