Aciclovir and neurotoxicity in hemodialysis: A 30-year-old story

Aciclovir is the standard treatment for herpes infections. Its almost exclusive renal elimination puts patients with end-stage renal disease at increased risk of accumulation and toxicity, warranting dosage adjustment. We report the cases of two chronic hemodialysis patients treated with aciclovir for herpes zoster who developed severe neurotoxicity despite dosages that were in line with or below current recommendations. The first patient received the recommended dose (800 mg twice daily), while the second was treated with a deliberately reduced dose (400 mg twice daily). Both patients developed acute encephalopathy associated with a cerebellar syndrome and behavioral disorders. Plasma levels were measured in one case and revealed supratherapeutic trough concentrations. Discontinuation of aciclovir, combined with intensified hemodialysis, led to rapid regression of symptoms and complete recovery. Our observations show that the dosage regimens currently recommended for hemodialysis patients can lead to significant overexposure and severe neurotoxicity. This neurotoxicity can also mimic herpes encephalitis, leading to inappropriate dose escalation and delayed diagnosis. There is a need to re-evaluate aciclovir dosage regimens in hemodialysis patients, favoring even lower doses, particularly in older patients, in order to prevent avoidable toxicity. In hemodialysis patients treated with aciclovir, the onset of neurological symptoms, after exclusion of herpes encephalitis, should raise suspicion of drug toxicity and lead to immediate discontinuation of treatment and intensification of dialysis.