Dementia: donepezil tied to doubled rhabdomyolysis risk

  • CMAJ

  • International Clinical Digest
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Takeaway

  • Short-term risk for rhabdomyolysis hospitalization was more than twice as high among older adults initiating donepezil (Aricept) vs rivastigmine (Exelon) or galantamine (Razadyne).

Why this matters

  • Emergence of this risk during postmarketing surveillance, but uncertainty about its incidence and severity.

 Key results

  • Compared with rivastigmine or galantamine, donepezil conferred higher 30-day risk for hospital admission with rhabdomyolysis:
    • Incidence: 0.06% vs 0.02%.
    • Weighted OR: 2.21 (95% CI, 1.52-3.22).
  • Donepezil-associated hospital admissions:
    • 12-day median length of stay.
    • 10% of patients admitted to ICU.
    • None treated with acute dialysis, mechanical ventilation.
  • Baseline statin use did not modify the observed association between donepezil and risk for hospital admission with rhabdomyolysis.

Study design

  • Canadian population-based retrospective cohort study 2002-2017 among 220,353 adults aged >65 years with a newly dispensed prescription for donepezil, rivastigmine, or galantamine.
  • Main outcome: hospital admission with rhabdomyolysis (from diagnostic codes) within 30 days of prescription.
  • Funding: Institute for Clinical Evaluative Sciences (ICES).

Limitations

  • Reliance on administrative data.
  • Inability to accurately capture falls (also a cause of rhabdomyolysis).
  • Exclusion of younger patients, patients prescribed doses outside those routinely recommended.
  • Grouping of rivastigmine and galantamine.

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