Case Presentation: 47 year-old male with PMH of hypertension, DM, CAD and ESRD on peritoneal dialysis, presented with altered mental status for 1 day. He had developed a vesicular rash in the right upper extremity and was diagnosed with herpes zoster at another facility 2 days prior, for which he was prescribed valacyclovir that was not renally dosed. After 5 doses he became more confused with erratic behaviour and had 3 falls. In the ED, he was confused, with unclear speech. He was afebrile, and no meningeal signs were noted. Labs showed hyperkalemia and metabolic acidosis. CT head was unremarkable. He was initially admitted to the medical floors, however he developed tonic clonic seizure-like activity and was transferred to the ICU for close monitoring. Repeat CT head was unchanged. He was loaded with Keppra however neurology recommended holding off any further doses as his seizures were thought to be due to valacyclovir toxicity. EEG showed no seizure activity. Acyclovir level on day 2 was 10 mcg/mL. Poison control recommended switching to hemodialysis for better drug clearance. Prior to his first hemodialysis session, he was obtunded, however after about 2 hours of hemodialysis, he became responsive to verbal stimuli and able to follow commands. After 2 hemodialysis sessions with marked improvement, he was transferred to the medical floors and transitioned back to peritoneal dialysis. He returned to his baseline and was discharged back home.
Discussion: Valacyclovir is a prodrug of acyclovir with greater bioavailability. After conversion and distribution throughout the body, Acyclovir is renally excreted. As such, renal impairment can lead to higher medication levels and possible toxicity. The patient in this case report was mistakenly prescribed the usual dose of 1 g 3 times daily rather than 500 mg every 48 hours for peritoneal dialysis patients. This led to accumulation of toxic levels of Acyclovir which resulted in the gradually worsening toxidrome.
Conclusions: The diagnosis of valacyclovir toxicity is largely clinical. Although plasma levels of the drug can be checked, direct correlation between the plasma level and symptoms have yet to be proven. Therefore, the constellation of symptoms in a patient with renal impairment who was recently started on valacyclovir should raise the index of suspicion.Prior to prescribing pharmacologic agents, it is very important for prescribers to gather a comprehensive history from the patient to identify any underlying conditions that require special dosing of the intended medications.