The estimated median lethal dose of donepezil hydrochloride following administration of a single oral dose in mice and rats is 45 and 32 mg/kg, respectively, or approximately 225 and 160 times the maximum recommend human dose of 10 mg per day.
Symptoms: Dose-related signs of cholinergic stimulation were observed in animals and included reduced spontaneuos movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, fasciculation and lower body surface temperature.
Overdose with cholinesterase inhibitors can result in cholinergic crisis characterized by severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.
Treatment: As in any case of overdose, general supportive measures should be utilised. Tertiary anticholinergics such as atropine may be used as an antidote for donepezil overdose. Intravenous atropine sulphate titrated to effect is recommended: an initial dose of 1.0 to 2.0 mg IV with subsequent doses based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when co-administered with quaternary anticholinergics such as glycopyrrolate. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (haemodialysis, peritoneal dialysis, or hemofiltration).