Animal Study Data
The estimated median lethal doses or lethal dose of donepezil hydrochloride following administration of a single oral dose in mice, rats and dogs is 45, 32 and 15 mg/kg, respectively, or approximately 98, 70 and 33 times the maximum recommended human dose of 23 mg per day. Dose-related signs of cholinergic stimulation were observed in animals and included reduced spontaneous movement, prone position, staggering gait, lacrimation, clonic convulsions, depressed respiration, salivation, miosis, fasciculation, tremors, and lower body surface temperature.
Symptoms of Overdosage
Overdosage 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 overdosage, general supportive measures should be utilized. Tertiary anticholinergics such as atropine may be used as an antidote for Donepezil hydrochloride overdosage. It is not known whether donepezil hydrochloride and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).
