Acyclovir Neurotoxicity in a Peritoneal Dialysis Patient: Report of a Case and Review of the Pharmacokinetics of Acyclovir

Abstract

Patient: Male, 80Final Diagnosis: Neurotoxicity due acyclovirSymptoms: Confusion • hallucinationMedication: AcyclovirClinical Procedure: —Specialty: NephrologyObjective:Unusual clinical courseBackground:The elderly population in the United States and the world is rapidly increasing. With aging, immunity and kidney function decrease, thus predisposing people to viral illnesses for which there is no effective prophylaxis. Herpes zoster afflicts the elderly and other immunocompromised patients, like those with end-stage renal disease, transplant recipients, and cancer patients, causing significant morbidity and sometimes mortality. Treating herpes zoster becomes problematic when the regular pharmacokinetics of the antiviral drugs are disturbed.Case Report:An 83-year-old African American man with end-stage kidney disease (ESRD) and on chronic peritoneal dialysis (PD) developed herpes zoster, for which he received the manufacturer-recommended intravenous dose of acyclovir. Shortly after taking the medication, he developed confusion, disorientation, and visual hallucinations. He was switched from PD to hemodialysis (HD), with successful recovery. Examination of the cerebrospinal fluid for meningitis and imaging studies of the head were negative. Serum levels of acyclovir were elevated.Conclusions:Even when the acyclovir dose is properly adjusted for kidney function based on the current manufacturer’s recommendations, it can cause neurotoxicity. Here, we discuss the pharmacokinetics of acyclovir and make some recommendations with regard to dose adjustment in patients with ESRD.

Severe mental disorders following anti-retroviral treatment in a patient on peritoneal dialysis: A case report and literature review

“…Valacyclovir-associated neurotoxicity usually occurs within 48-72 h of treatment start, and the symptoms can be gradually relieved after the drug is discontinued for 4-14 d (Table 1). For the patient in the present study, the time of onset and duration of symptoms were similar to those reported in literature[14,16-25] (Table 1).…”

“…Since acyclovir is mainly cleared by the kidneys, it is a consensus to reduce its dose in patients with renal failure[25]. The dose is mainly determined by a combination of factors such as different methods of dialysis, residual renal function, hydration, and age.…”

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

“…Ninety‐seven of those were included in the analysis, representing a total of 119 independent patients (Figure 1). The cases were extracted from 86 clinical cases 9‐35,37‐48,50‐54,56‐63,65‐71,73,75‐77,80‐83,85‐100,102,103 and 11 case series 36,49,55,64,72,74,78,79,84,101,113 . Figure 1 shows the case selection flow diagram.…”

“…Detection of acyclovir levels in plasma was requested in 53 cases (44.5%), with a mean of 17.2 mcg/ml ±25.3, and levels in CSF in 10 cases, 15,17,18,26,31,113 with a mean of 1.2 mcg/ml ±1.6. The CMMG metabolite was also obtained in 10 cases, 25,31,34,37,51,113 with 8 determinations in plasma, 8 in CSF and 1 in urine.…”

Current Antivirals and Novel Botanical Molecules Interfering With Herpes Simplex Virus Infection

“…Other limitations related to the treatment with ACV also exist. For instance, oral intake of ACV has an absorption efficiency of only 15-30% (Bean, 1992), and previous reports indicated that senior patients that had renal problems could experience significant neurotoxicity, because they were not able to properly excrete this drug (Chau, 2018). Another important limitation associated to ACV is the ability of HSV-1 and HSV-2 to mutate and generate variants that are resistant to this drug by acquiring point mutations in the gene encoding for the viral thymidine kinase (TK), which decreases enzyme expression or modifies substrate specificity abrogating acyclovir phosphorylation, or by acquiring mutations in the gene encoding for the viral DNA polymerase (UL30), which may enable HSV-1 and HSV-2 to replicate in the presence of ACV (Reusser, 1996).…”