Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study

Abstract

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04–4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98–5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13–10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.

Valacyclovir-Associated Catatonia

“…A systematic review of reported cases of neurotoxicity associated with acyclovir/valacyclovir showed that 83.3% of cases had renal dysfunction 5 . A large population-based study found that patients treated with valacyclovir for treatment of herpes zoster infection who were on dialysis had higher risk of developing AMS than those who were not 6 …”

A Case Report of Valacyclovir-Associated Neurotoxicity in End-Stage Renal Disease: A Rare but Preventable Side Effect

“…With increasing recognition of VAN, one population-based retrospective study examined patients with ESRD on dialysis with individuals with normal renal function. The study found that the incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users [ 9 ]. However, ESRD patients on adjusted valacyclovir doses and receiving regular, timely dialysis without missing sessions did not have VAN side effects [ 9 ].…”

“…The study found that the incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users [ 9 ]. However, ESRD patients on adjusted valacyclovir doses and receiving regular, timely dialysis without missing sessions did not have VAN side effects [ 9 ]. Patients on hemodialysis taking a valacyclovir dose of less than 500 mg three times per week and patients on peritoneal dialysis taking a dose of less than 500 mg per day did not have altered mental status [ 9 ].…”

“…However, ESRD patients on adjusted valacyclovir doses and receiving regular, timely dialysis without missing sessions did not have VAN side effects [ 9 ]. Patients on hemodialysis taking a valacyclovir dose of less than 500 mg three times per week and patients on peritoneal dialysis taking a dose of less than 500 mg per day did not have altered mental status [ 9 ]. VAN can be preventable if patients with ESRD are on renally adjusted valacyclovir doses and monitored closely while on medications.…”

Varicella Zoster vaccination in hemodialysis patients: The state of the art

“…Because valacyclovir is excreted through the kidneys, patients with impaired renal function might be the most susceptible to valacyclovir-associated neurotoxicity. 11 …”