Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study

Fleet, Jamie L.; McArthur, Eric; Patel, Aakil; Weir, Matthew A.; Montero‐Odasso, Manuel; Garg, Amit X.

doi:10.1503/cmaj.190337

Cited by 13 publications

(8 citation statements)

References 25 publications

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“…171 Rhabdomyolysis and neuroleptic malignant syndromes are uncommon side effects which have been reported in older adults receiving donepezil. [173][174][175] Furthermore, hemolytic anemia, syndrome of inappropriate antidiuretic hormone (SIADH), 161 and severe hepatitis 176 also present as uncommon adverse effects in clinical practice. AChEI-induced adverse effects may provide chance for prescribing cascades.…”

Section: Uncommon Adverse Effectsmentioning

confidence: 99%

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Ruangritchankul¹,

Chantharit²,

Srisuma³

et al. 2021

TCRM

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The rising of global geriatric population has contributed to increased prevalence of dementia. Dementia is a neurodegenerative disease, which is characterized by progressive deterioration of cognitive functions, such as judgment, language, memory, attention and visuospatial ability. Dementia not only has profoundly devastating physical and psychological health outcomes, but it also poses a considerable healthcare expenditure and burdens. Acetylcholinesterase inhibitors (AChEIs), or so-called anti-dementia medications, have been developed to delay the progression of neurocognitive disorders and to decrease healthcare needs. AChEIs have been widely prescribed in clinical practice for the treatment of Alzheimer's disease, which account for 70% of dementia. The rising use of AChEIs results in increased adverse drug reactions (ADRs) such as cardiovascular and gastrointestinal adverse effects, resulting from overstimulation of peripheral cholinergic activity and muscarinic receptor activation. Changes in pharmacokinetics (PK), pharmacodynamics (PD) and pharmacogenetics (PGx), and occurrence of drug interactions are said to be major risk factors of ADRs of AChEIs in this population. To date, comprehensive reviews in ADRs of AChEIs have so far been scarcely studied. Therefore, we aimed to recapitulate and update the diverse aspects of AChEIs, including the mechanisms of action, characteristics and risk factors of ADRs, and preventive strategies of their ADRs. The collation of this knowledge is essential to facilitate efforts to reduce ADRs of AChEIs.

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Section: Uncommon Adverse Effectsmentioning

confidence: 99%

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Ruangritchankul¹,

Chantharit²,

Srisuma³

et al. 2021

TCRM

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show abstract

“…Fleet et al in 2019, for example, found that "donepezil was associated with a higher risk of hospital admission [for] rhabdomyolysis compared [to] rivastigmine or galantamine," with the rationale of the study being based upon a Health Canada alert for donepezil. 10 Post-marketing surveillance may indicate there are important differences within AChEIs with regards to safety. Among other emerging adverse effects that have arisen in recent years is the potentially fatal arrhythmia that can result from donepezil.…”

Section: Efficacy and Safety Differences Between The Three Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Huang

Alsabbagh

2020

Pharmacology Res & Perspec

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Donepezil, galantamine, and rivastigmine are the three acetylcholinesterase inhibitors (AChEIs), out of a total of only four medications prescribed in the treatment of Alzheimer's Disease (AD) and related dementias. These medications are known to be associated with bradycardia given their mechanism of action of increasing acetylcholine (ACh). However, in March 2015, donepezil was added to the CredibleMeds “known‐risk” category, a list where medications have a documented risk for acquired long‐QT syndrome (ALQTS) and torsades de pointes (TdP) – a malignant ventricular arrhythmia that is a different adverse event than bradycardia (and is not necessarily associated with ACh action). The purpose of this article is to review the three AChEIs, especially with regards to mechanistic differences that may explain why only donepezil poses this risk; several pharmacological mechanisms may explain why. However, from an empirical point‐of‐view, aside from some case‐reports, only a limited number of studies have generated relevant information regarding AChEIs' and electrocardiogram findings; none have specifically compared donepezil against galantamine or rivastigmine for malignant arrhythmias such as TdP. Currently, the choice of one of the three AChEIs for treatment of AD symptoms is primarily dependent upon clinician and patient preference. However, clinicians should be aware of the potential increased risk associated with donepezil. There is a need to examine the comparative risk of malignant arrhythmias among AChEIs users in real‐world practice; this may have important implications with regards to changes in AChEI prescribing patterns.

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“…6 Although there are no proven modalities to prevent AD, healthy diet, physical activity, omega-3 fatty acid supplementation, cognitive engagement, and low alcohol consumption have also shown potential in this area. [7][8][9] Medications used for treatment of AD include cholinesterase inhibitors and partial N-methyl-D-aspartate (NMDA) antagonists, which modulate either acetylcholine or glutamate (Table 1 [10][11][12][13][14][15][16][17][18][19] ). Donepezil, rivastigmine, and galantamine are cholinesterase inhibitors used for treatment of mild to moderate disease.…”

mentioning

confidence: 99%

“…11 A recent population-based cohort study found that initiating donepezil is associated with a higher 30-day risk of admission to hospital due to rhabdomyolysis when compared to rivastigmine or galantamine. 12 This risk, however, has been estimated to be low. 12 In general, only 1 cholinesterase inhibitor should be tried at a time, and centrally acting anticholinergic medications such as diphenhydramine, tricyclic antidepressants, and oxybutynin should be avoided because these counteract the effects of the cholinesterase inhibitors.…”

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Pharmacists a valuable resource for patients with Alzheimer disease and their caregivers

Bethishou¹,

Lewis²

2019

Journal of the American Pharmacists Association

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Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study

Cited by 13 publications

References 25 publications

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Adverse Drug Reactions of Acetylcholinesterase Inhibitors in Older People Living with Dementia: A Comprehensive Literature Review

Comparative risk of cardiac arrhythmias associated with acetylcholinesterase inhibitors used in treatment of dementias – A narrative review

Pharmacists a valuable resource for patients with Alzheimer disease and their caregivers

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