Quick Take: Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine

1. Donepezil is associated with an elevated short-term risk of hospital admission for rhabdomyolysis compared to rivastigmine or galantamine for Alzheimer’s disease and dementia.

Evidence Rating Level: 2 (Good)

Regulatory agencies have issued a post-marketing surveillance warning regarding the risk of rhabdomyolysis with donepezil use, commonly used in managing symptoms of Alzheimer’s disease and dementia. The Pharmacovigilance Databases of the United States and Canada data indicated that such events occurred more frequently with donepezil than with other cholinesterase inhibitors. It is unclear whether rivastigmine and galantamine are associated with a risk of rhabdomyolysis. In this population-based retrospective cohort study from Ontario, Canada (2002-2017), researchers examined whether the initiation of donepezil was associated with a higher risk of 30-day hospital admission with rhabdomyolysis compared to rivastigmine and galantamine in patients age 66 years or older. Overall, records from 152,300 patients with newly dispensed prescriptions for donepezil and 68,053 patients with prescriptions for rivastigmine or galantamine were analyzed. Researchers found that donepezil was associated with a higher risk of rhabdomyolysis-associated hospital admission (88 events, 0.06%) compared to rivastigmine or galantamine (16 events, 0.02%) (weighted OR 2.21, 95% CI 1.52 to 3.22). The majority of hospital admissions following donepezil prescription were not severe. The findings of this study therefore indicate that donepezil may be associated with an elevated short-term risk of hospital admission for non-severe rhabdomyolysis compared to other commonly used agents.

Click to read the study in CMAJ

Image: PD

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