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Overdose: 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: Tertiary anticholinergics such as atropine may be used as an antidote for donepezil overdosage. Intravenous (IV) atropine titrated to effect is recommended: an initial dose of 1 to 2 mg IV with subsequent dose based upon clinical response. Atypical responses in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quarternary anticholinergics such as glycopyrrolate. It is not known whether donepezil and/or its metabolites can be removed by dialysis (e.g., hemodialysis, peritoneal dialysis, hemofiltration).
