A 46-year-old male with a history of end-stage renal disease (ESRD) on dialysis was brought to the emergency department by his family for intense, new-onset visual hallucinations.
Just prior to ED arrival, he visited his ophthalmologist for a routine evaluation. Shortly after leaving this appointment, he started experiencing vivid hallucinations of being on a farm and seeing children run past him.
He denied any infectious symptoms, trauma, recreational drug use, or pain. His vital signs were unremarkable. On exam, the patient was alert, oriented, and spoke in full sentences. He maintained insight and knew the hallucinations were not real, but continued to see things that were not there. His neurological exam was unremarkable.
Family members at the bedside reported he seemed different compared to his usual self, although they were unable to describe specific new behaviors other than the visual symptoms.
Diagnosis / Management
An ophthalmology note from the patient’s routine visit earlier in the day noted baseline visual acuity and did not reveal any clues to the patient’s acute change in presentation. Further chart review was significant for a recent admission due to a malfunctioning AV fistula requiring a fistulogram. The patient was discharged a few days prior to ED presentation with his home medications refilled. While reviewing this discharge summary, the ED resident noticed a prescription for valacyclovir: 1g three times per day.
As there was no documented indication for antiviral therapy, this medication may have been inadvertently prescribed or refilled at discharge. Nevertheless, the patient had diligently taken several doses.
The plasma elimination half-life of the delivered acyclovir by valacyclovir in those with normal renal function is averaged at 2.5-3.3 hours, while the half-life for those with ESRD is averaged at approximately 14 hours.1 Thus, the recommended dosing of valacyclovir for patients with renal disease differs depending on the indication and the level of renal impairment. Some dosing regimens are as low as 500mg every two days.1 The patient’s prescription had not been adjusted for his renal impairment, and as a result, he ingested approximately 6 times the recommended dose prior to presenting to the ED.
Symptoms from valacyclovir toxicity range widely in severity, from general malaise to coma. As seen in this patient, toxicity can cause central nervous system (CNS) effects including agitation, hallucinations, confusion, and encephalopathy.1 Non-neurological sequelae such as acute kidney injury and thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) have also been reported.1
The Poison Control Center was consulted. Given the patient’s relatively mild encephalopathy, they encouraged regularly scheduled dialysis to assist with valacyclovir clearance. The patient was noted to grow progressively more agitated and delirious over the next day, but his mental status rapidly returned to baseline after dialysis without recurrence of visual hallucinations. He continued to do well and was discharged after a brief hospital stay.
TAKE-HOME POINTS
- Medications often require patient-specific dosing adjustments to avoid adverse effects. Even medications that we view as relatively low-risk can cause severe toxicity.
- A thorough medication reconciliation is required for all patients with altered mental status, especially for patients who have recently interacted with the health care system. Errors in medication prescription can lead to serious consequences and even toxicity, as demonstrated in this case.
- Symptoms of valacyclovir toxicity can range in severity. CNS effects range from general malaise to hallucinations, agitation, and coma. They are most often seen in patients with renal impairment.2 Early identification and intervention, such as dialysis in severe cases to assist with metabolite clearance, can lead to favorable outcomes.3
REFERENCES
- U.S. Food and Drug Administration. Drug Label Information: NDA 020487/S-022. 2021
- Wang YC, Juan SH, Li CH, Chou CL, Chen LY, Chien LN, Fang TC. Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study. Front Med (Lausanne). 2022 Sep 20;9:997379. doi: 10.3389/fmed.2022.997379
- Asahi T, Tsutsui M, Wakasugi DM, Tange D, Takahashi C, Tokui K, Okazawa S, Okudera H. Valacyclovir neurotoxicity: clinical experience and review of the literature. Eur J Neurol. 2009;16(4):457–60. doi: 10.1111/j.1468-1331.2008.02527
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