Alzheimer’s drug increases risk of muscle breakdown

A drug commonly used to manage symptoms of Alzheimer’s disease and other dementias may double the risk of rhabdomyolysis, a painful condition of muscle breakdown that can affect the kidneys, according to a Western study.

The study, Risk of rhabdomyolysis with donepezil compared with rivastigmine or galantamine: a population-based cohort study, was published recently in the Canadian Medical association Journal.

Led by Western and Lawson Health Research Institute researchers, the study looked at data from 2002-17 on 220,353 patients aged 66 years or older in Ontario, with a new prescription for donepezil, rivastigmine or galantamine – three inhibitors used to manage dementia and Alzheimer’s disease.

Donepezil, the leading drug used for treatment of Alzheimer’s, is prescribed to millions of Canadians dealing with the disease, with almost 10 million patients worldwide are given a new diagnosis each year.

“The relative risk was small but statistically significant, and most hospital admissions were not severe,” said Dr. Amit Garg, a Schulich School of Medicine & Dentistry professor and Lawson scientist. “Patients should not be alarmed. The chance of being hospitalized with rhabdomyolysis after starting donepezil remains very low and they should not discontinue their prescription medication without speaking to their doctor.”

Rhabdomyolysis damages the kidneys, and in the most severe forms need dialysis treatments to survive.

In 2015, Health Canada and the U.S. Food and Drug Administration issued warnings about the risk of rhabdomyolysis with donepezil. This warning, however, was based on fewer than 100 cases.

With data provided through the Institute for Clinical Evaluative Sciences, the Western-led study looked at a larger cohort and compared their 30-day risk of a hospital admission with rhabdomyolysis to patients newly prescribed other drugs used to treat Alzheimer’s disease.

While there was a two-fold higher risk of rhabdomyolysis with donepezil, Garg said the risk for patients remains low. Even if the study were underestimating the risk by 10-fold, still the increased risk of a hospital admission with rhabdomyolysis is only one in every 300 patients.

“We saw that even though they were admitted to hospital, the rhabdomyolysis was not so severe to require a patient to receive urgent dialysis or a mechanical ventilator,” he said, adding it’s important for physicians to be mindful of the possible risk to their patients who are using donepezil.

“If someone presents to the hospital with rhabdomyolysis, they should look for donepezil on their medication list as a possible cause. If a patient is tolerating the drug and has no difficulties in the first 30 days, and they remain on the same dose, the chance they will develop rhabdomyolysis in the future would be expected to be quite low.”

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