Canada Issues Warnings on Alzheimer’s Disease Drugs

To get the most accurate and up-to-date information regarding commonly prescribed medications, often it is worth looking to the actions of other countries’ health agencies, especially since most are more vigilant than the U.S. Food and Drug Administration (FDA). Recently, Health Canada, the Canadian equivalent of the FDA, alerted doctors and patients to safety concerns about two commonly used drugs for Alzheimer’s disease. Public Citizen’s Health Research Group lists both of these drugs as Do Not Use.

Two side effects of donepezil

On Jan. 21, Health Canada issued a warning concerning two rare but potentially very serious adverse effects of the drug donepezil (ARICEPT, ARICEPT-23).[1]

Donepezil is approved for the treatment of Alzheimer’s disease. Generic versions are available from more than 20 different companies in the U.S.[2] Donepezil is available either alone or, as of December 2014, in combination with memantine (NAMZARIC), another drug approved for Alzheimer’s disease.[3] We have long designated donepezil as a Do Not Use drug because of its poor efficacy.

The first warning from Health Canada concerns the risk for rhabdomyolysis, a condition that results in the breakdown of muscle. Symptoms include muscle pain, fever, weakness, nausea and dark urine. If untreated, it can lead to kidney failure and abnormal heart rhythms.[4] The risk is increased if the patient is taking other drugs known to cause rhabdomyolysis, such as statins, antipsychotics and certain classes of antidepressants (selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors).[5]

The second warning concerns risk for a life-threatening condition known as neuroleptic malignant syndrome (NMS). Symptoms of NMS include fever, mental status changes, agitation, delirium and muscle rigidity (which, in turn, can lead to rhabdomyolysis).

Health Canada found a total of 88 cases of rhabdomyolysis (three fatal) and 67 cases of NMS (nine fatal) internationally that had been reported to the manufacturer of brand-name donepezil products. In most cases, patients had only one of these conditions, but some suffered both. The FDA has not yet issued any similar warnings concerning these two serious adverse events.

Skin reactions with galantamine

On Nov. 18, 2014, Health Canada[6] issued a warning that the Alzheimer’s disease drug galantamine (RAZADYNE, RAZADYNE ER) has been associated with rare but serious, potentially fatal skin reactions.

These skin reactions may include:

• Severe rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals.
• Red rash covered with small pus-filled bumps that can spread over the body, sometimes with a fever.
• Rash that may blister with spots that look like small targets.[7]

The most dangerous of these reactions is the blistering rash with peeling skin, which may indicate Stevens-Johnson syndrome. A medical emergency, Stevens-Johnson syndrome causes skin damage similar to that caused by severe burns and usually requires hospitalization.

The FDA has not yet provided similar warnings about these products to health care providers in the U.S.

Public Citizen’s Health Research Group also has designated galantamine as Do Not Use because it is minimally effective and has been linked to gastrointestinal and cardiovascular side effects.[8]

What You Can Do

If you or a loved one is taking either of these two drugs, contact your or your loved one’s health care provider to discuss stopping the drug. Do not stop these or any drugs without consulting your health care provider.

If you notice any of the symptoms listed above while still taking these drugs or in a loved one who is taking these drugs, seek medical attention immediately.

Be sure to report serious adverse events from drugs to the FDA’s MedWatch adverse event reporting program at https://www.accessdata.fda.gov/scripts/medwatch or by calling 800-FDA-1088.

References

[1] Health Canada. Summary safety review — Aricept (donepezil) — risk of rhabdomyolysis and neuroleptic malignant syndrome. January 21, 2015. http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/aricept-eng.php. Accessed February 5, 2015

[2] Food and Drug Administration. Orange book: Approved drug products with therapeutic equivalence evaluations. Updated December 2014. http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm. Accessed February 5, 2015.

[3] Food and Drug Administration. Drugs@FDA. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm. Accessed February 5, 2015.

[4] Health Canada. Summary safety review — Aricept (donepezil) — risk of rhabdomyolysis and neuroleptic malignant syndrome. January 21, 2015. http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/aricept-eng.php. Accessed February 5, 2015.

[5] Health Canada. Alzheimer's drug Aricept (donepezil) - New warnings on the serious risks of muscle breakdown and of a neurological disorder. January 21, 2015. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/43469a-eng.php. Accessed February 5, 2015.

[6] Healthy Canadians. REMINYL ER (galantamine hydrobromide) - New Safety Information Regarding the Risk of Serious Skin Reactions - For the Public. November 18, 2014. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/42237a-eng.php. Accessed December 1, 2014.

[7] Healthy Canadians. REMINYL ER (galantamine hydrobromide) - New Safety Information Regarding the Risk of Serious Skin Reactions - For the Public. November 18, 2014. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/42237a-eng.php. Accessed December 1, 2014.

[8] WorstPills.org. Drug profile — galantamine. /monographs/view/129. Accessed December 1, 2014.