Donepezil overdose: a tenfold dosing error.
OBJECTIVE
To report toxicity resulting from donepezil administration following a tenfold dosing error.


METHODS
A 79-year-old white nursing home patient with a history of Alzheimer disease and hypertension was inadvertently given 50 mg of donepezil instead of her usual 5-mg dose. She presented to the emergency department with nausea, vomiting, and persistent bradycardia (HR in the 40s). Routine laboratory studies were all within normal limits. Basilar rales were noted five hours after arrival. She was treated with atropine 0.2 mg as needed for bradycardia (HR <50 beats/min); a total of 3.0 mg was administered over 18 hours. Each bolus kept her HR >60 beats/min for one-half to two hours. No further vomiting or evidence of pulmonary edema occurred after her initial episodes. She returned to baseline by day 2 (HR in the 70s) and was returned to the nursing home.


CONCLUSIONS
Donepezil is a centrally acting, reversible cholinesterase inhibitor that is used in the treatment of Alzheimer disease. Donepezil is highly specific for neural acetylcholinesterases, preferentially binding acetylcholinesterase by greater than three orders of magnitude over butyrylcholinesterases. This specificity minimizes peripheral adverse effects at therapeutic doses. Our patient mainly experienced bradycardia and had minimal secretory effects compared with what is usually seen with nonspecific cholinesterase inhibition. Medication errors like the one that produced this overdose are a common but preventable cause of morbidity in healthcare facilities.


CONCLUSIONS
A tenfold dosing error caused donepezil toxicity. The main effect of this overdose was bradycardia, which responded to atropine therapy.
Shepherd
G
G
Maryland Poison Center, School of Pharmacy, University of Maryland, Baltimore, USA. gsheph@parknet.pmh.org
Klein-Schwartz
W
W
Edwards
R
R
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy; D001285:Atropine / Q000627:therapeutic use; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000506:poisoning* / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000506:poisoning* / Q000627:therapeutic use; D008508:Medication Errors; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage* / Q000506:poisoning* / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D007189:Indans; D018727:Muscarinic Antagonists; D010880:Piperidines; D001285:Atropine; D000077265:Donepezil