Canadian researchers have found that hospitalization for rhabdomyolysis, a rare muscle condition, occurred more than twice as frequently among those taking the Alzheimer’s drug donepezil (Aricept) compared with those taking two similar drugs, rivastigmine (Exelon) and galantamine (Razadyne).

Published in the Canadian Medical Association Journal in September, researchers conducted an analysis of the medical records of 220,353 patients age 66 and older from 2002 to 2017, focused on hospitalizations within 30 days of initiating drug treatment. The research is known as a “retrospective cohort study,” which is an observational investigation that examines archived data to understand risk.

What is Rhabdomyolysis?

Rhabdomyolysis is a very rare but serious condition in which injured skeletal muscles leak potential toxins from dead muscle cells into the bloodstream. While timely treatment generally results in positive outcomes, the condition can lead to complications such as kidney failure and even death.

Common symptoms of rhabdomyolysis include muscle pain in the shoulders, lower back or thighs, arm and leg muscle weakness, and very dark or decreased urination. However, there are many possible causes of rhabdomyolysis, including seizures, some viral infections, metabolic disorders and physical traumas, among others.   

About Alzheimer's Medications

There are two types of drugs used to treat Alzheimer's: cholinesterase inhibitors and memantine. The three drugs compared in the study are all cholinesterase inhibitors, which are more commonly prescribed. Of the drugs studied, Aricept is the most popular.

Cholinesterase inhibitors act by blocking the breakdown of the neurotransmitter acetylcholine. Acetylcholine aids memory by transmitting messages between cells and a deficit of acetylcholine is believed to be involved in Alzheimer’s disease. Cholinesterase inhibitors are used for early to moderate stages of dementia, while the other type of dementia drug, memantine (Namenda), is used for moderate to severe stages.

Lead study author Jamie Fleet told Medscape Medical News that most of the rhabdomyolysis cases were not severe and that none of the hospitalized patients required acute dialysis or mechanical ventilation. Fleet, a resident in the Department of Physical Medicine and Rehabilitation at McMaster University, said the actual incidence of hospitalization within 30 days of beginning treatment remains reassuringly low.

The findings do, however, support regulatory agency warnings about the risk of donepezil-induced rhabdomyolysis.


"Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study." Canadian Medical Association Journal. 16 September 2019. Jamie L. Fleet et al.