Donepezil Ups Risk for Hospital Admission for Rhabdomyolysis

Initiating donepezil to manage symptoms of Alzheimer disease or other dementias is associated with a higher risk for 30-day admission to the hospital with rhabdomyolysis compared with initiating rivastigmine or galantamine, according to a study published in the issue of CMAJ, the journal of the Canadian Medical Association.

Jamie L. Fleet, M.D., from McMaster University in Hamilton, Ontario, Canada, and colleagues conducted a retrospective cohort study to examine the 30-day risk for hospital admission with rhabdomyolysis associated with initiating donepezil versus other cholinesterase inhibitors. Participants were adults aged 66 years or older with a newly dispensed prescription for donepezil versus rivastigmine or galantamine.

The researchers found that compared with rivastigmine or galantamine, donepezil correlated with an elevated risk for hospital admission with rhabdomyolysis (0.06 versus 0.02 percent; weighted odds ratio, 2.21). Hospital admissions with rhabdomyolysis after donepezil use were mostly not severe, and no patients were treated with acute dialysis or mechanical ventilation.

"The biological mechanism of donepezil-associated rhabdomyolysis is unknown," the authors write. "Acetylcholine is known to play a role in action potential transmission across the neuromuscular junction, leading to muscle contraction. Theoretically, preventing the breakdown of acetylcholine may lead to abnormalities in muscle contraction and ultimately rhabdomyolysis. This area warrants further research."

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