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Objective: To report a case of acute renal failure and neurotoxicity following administration of oral acyclovir., Data Sources: Medical record of the patient, case reports identified by MEDLINE., Data Extraction: Data were abstracted from relevant published data by Johnson and reviewed by the remaining authors., Case Summary: A 69-year-old woman was diagnosed with herpes zoster and oral acyclovir was prescribed by her local physician. After approximately two days the patient was taken to the emergency department of a local hospital with signs of acute confusion and acute renal failure. Medications included oxycodone/acetaminophen, alprazolam, prazepam, and digoxin. Pertinent laboratory abnormalities included serum digoxin 4.1 mumol/L, white blood cell count 17.6 x 10(9)/L, blood urea nitrogen (BUN) 24 mmol/L of urea, and serum creatinine 305 mumol/L (patient baseline is 11 mmol/L of urea and 91.5 serum creatinine mumol/L, respectively). Because of increasing lethargy and a focal seizure, she was transferred to our institution. Despite an extensive workup, no organic cause of her altered mental status and acute renal failure was identified. Four days after discontinuation of the acyclovir, without specific intervention, the patient's mental status improved and her BUN and serum creatinine concentrations had decreased to 21 mmol/L of urea and 190.6 mumol/L, respectively. On day 5, the patient was alert and oriented to name, place, year, and month. On day 9, her renal function and mental status had returned to baseline and she was discharged., Conclusions: Acute renal failure and neurotoxicity are usually associated with intravenous acyclovir. The temporal relationship between the initiation of oral acyclovir therapy and the onset of adverse events, supported by published data of a few similar cases, strongly implicate oral acyclovir as the cause of this patient's acute renal failure and neurotoxicity. This case suggests that elderly patients with mild increased serum creatinine concentrations may be at increased risk and should be monitored closely for signs and symptoms of acute renal failure and neurotoxicity.