RT Journal Article
SR Electronic
T1 Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study
JF Canadian Medical Association Journal
JO CMAJ
FD Canadian Medical Association
SP E1018
OP E1024
DO 10.1503/cmaj.190337
VO 191
IS 37
A1 Fleet, Jamie L.
A1 McArthur, Eric
A1 Patel, Aakil
A1 Weir, Matthew A.
A1 Montero-Odasso, Manuel
A1 Garg, Amit X.
YR 2019
UL http://www.cmaj.ca/content/191/37/E1018.abstract
AB BACKGROUND: Donepezil, rivastigmine and galantamine are popular cholinesterase inhibitors used to manage the symptoms of Alzheimer disease and other dementias; regulatory agencies in several countries warn about a possible risk of rhabdomyolysis with donepezil, based on information from case reports. Our goal was to investigate the 30-day risk of admission to hospital with rhabdomyolysis associated with initiating donepezil versus other cholinesterase inhibitors.METHODS: We conducted a retrospective cohort study in Ontario, Canada, from 2002 to 2017. Participants were adults aged 66 years or older with a newly dispensed prescription for donepezil compared with rivastigmine or galantamine. The primary outcome was hospital admission with rhabdomyolysis (assessed using hospital diagnostic codes) within 30 days of a new prescription of a cholinesterase inhibitor. Odds ratios were estimated using logistic regression, with inverse probability of treatment weights calculated from propensity scores.RESULTS: The average age in our 2 groups was 81.1 years, and 61.4% of our population was female. Donepezil was associated with a higher risk of hospital admission with rhabdomyolysis compared with rivastigmine or galantamine (88 events in 152 300 patients [0.06%] v. 16 events in 68 053 patients [0.02%]; weighted odds ratio of 2.21, 95% confidence interval [CI] 1.52–3.22). Most hospital admissions with rhabdomyolysis after donepezil use were not severe, and no patient was treated with acute dialysis or mechanical ventilation.INTERPRETATION: Initiating donepezil is associated with a higher 30-day risk of admission to hospital with rhabdomyolysis compared with initiating rivastigmine or galantamine. The proportion of patients who develop severe rhabdomyolysis within 30 days of initiating donepezil is very low.