Donepezil overdose - trending levels and symptoms

Abstract

Background: Donepezil (DPZ) is a reversible, central anticholinesterase inhibitor used in the treatment of mild to moderate dementia and more recently in the treatment of mild cognitive impairment. Case reports of overdose describe symptomatic bradycardia, complete AV block, respiratory insufficiency, and syncope. We report an unintentional DPZ overdose with serum levels in a patient who developed symptomatic bradycardia, was treated with atropine and recovered over the course of three days. Case report: A 53-year-old otherwise healthy man with a history of memory loss was placed on DPZ by his primary doctor six months prior to presenting for an acute accidental overdose of up to twenty 10 mg DPZ tablets, a dose 20 - 40 times the usual daily dose. The patient reported ingesting the pills when he mistook the bottle for his multivitamins. He presented to the Emergency Department (ED) via EMS thirty to sixty minutes after the ingestion. He was confused, somnolent and diaphoretic with a heart rate (HR) in the 30s-50s. An ECG demonstrated sinus bradycardia. The patient was given 1 mg intravenous atropine with minimal response. He was admitted to the medical intensive care unit for monitoring and supportive care. Serum levels of DPZ were trended, with the initial level drawn in the ED showing 100 ng/ml and final level drawn at 60 hours showing 37 ng/ml. His confusion, diaphoresis and somnolence resolved over the first 16 hours and the bradycardia persisted for 52 hours. Despite his bradycardia he remained normotensive throughout his hospital stay. He was discharged on the third hospital day, asymptomatic with a HR of 64. Case discussion: Donepezil is a likely medication for overdose given the patient population for whom it is prescribed. Patients with memory loss may unintentionally take additional doses of their medications. Since most patients with memory loss are elderly, they are more likely to have co-morbid conditions such as underlying cardiac disease and conduction system abnormalities that would put them at higher risk of a poor outcome in the case of a DPZ overdose. Conclusion: We present a case of symptomatic DPZ overdose with trending of DPZ levels over 60 hours. This patient had marked cardiovascular symptoms, but did well following one dose of atropine and subsequent supportive care. This case highlights the time course of DPZ toxicity and correlates symptoms with serum levels.