A 95-year-old female with a history of stage III chronic kidney disease (CKD), heart failure with reduced ejection fraction (HFrEF), and dementia with baseline orientation only to person and place, presented to the emergency department (ED) for upper extremity myoclonic jerking for one day. Her review of systems upon initial presentation was negative other than for a dry cough. Her physical exam was significant for left lower-quadrant tenderness and upper-extremity myoclonus.

Upon reviewing her past medical history, she was recently started on valacyclovir, 1,000 mg, three times per day for shingles. She had blood laboratory testing done along with a urinalysis (showing only stable CKD), a chest X-ray, and a CT scan of her head and abdomen, which showed no acute abnormalities. She was subsequently discharged to her nursing facility.

Three days later, she presented back to the ED for altered mental status and persistent myoclonus. She had reduced oral intake, was unable to participate in her activities of daily living, and was more aggressive toward staff members at her skilled nursing facility. Her physical exam revealed intermittent agitation and upper extremity myoclonus, but no meningismus.

Diagnosis and Outcome

During her second emergency department visit, an infectious and metabolic workup was performed, demonstrating acute kidney injury (AKI), but otherwise no acute abnormalities. She was admitted to the hospital for AKI and suspected valacyclovir-associated neurotoxicity in the setting of an AKI. Her valacyclovir was discontinued during her hospitalization and her myoclonus resolved. She was discharged at her baseline mental status.

Discussion

Antivirals are the treatment of choice for patients diagnosed with shingles; valacyclovir is often preferred due to its bioavailability and dosing regimen. Valacyclovir shares a similar mechanism of action to acyclovir, another drug of choice in treatment for herpes zoster, and shares a very favorable and similar side effect profile. Nausea and vomiting are reported as the most common side effects with these medications.¹ Rare side effects of valacyclovir include neurotoxicity, nephrotoxicity, psychomotor disturbances, and hepatotoxicity.

These side effects can be linked to the pharmacokinetics of the drug. Valacyclovir is metabolized hepatically and excreted renally. In patients with either hepatic or renal impairment, toxic metabolites can precipitate crystal deposition in the renal tubules leading to acute kidney injury, whereas the accumulation of toxic metabolites in cerebrospinal fluid can lead to neuropsychiatric symptoms.^2,3 Although the incidence of neurotoxicity associated with valacyclovir has not been elucidated, numerous case reports identify a wide array of neuropsychiatric symptoms that can be seen with valacyclovir toxicity, ranging from altered mental status to hallucinations and dysarthria.