HEALTH CANADA WARNS OF DANGEROUS DRUG INTERACTION

August 28, 2015

Here’s an important alert for patients taking either repaglinide-containing medications (PRANDIN; PRANDIMET) or clopidogrel (PLAVIX).

On July 31, 2015, Health Canada, Canada’s drug regulatory agency, released a warning of the potential risk of dangerously low blood sugar levels when repaglinide-containing medications and clopidogrel are taken together. The agency therefore warned against using the drugs together, under any circumstances.[1]

Repaglinide is marketed, both on its own (PRANDIN) and in combination with the diabetes medication metformin (PRANDIMET), for the treatment of Type 2 diabetes. Clopidogrel is approved to reduce the risk of heart attacks and strokes in patients with cardiovascular disease. Public Citizen’s Health Research Group previously has designated repaglinide as Do Not Use and clopidogrel as Limited Use.

Health Canada based its decision on a study conducted in nine healthy subjects who were given repaglinide with and without clopidogrel over separate three-day periods.[2] Clopidogrel increased the concentration of repaglinide in the blood to levels four to five times higher than when repaglinide was given alone. This resulted in a significant drop in blood sugar levels.

The Food and Drug Administration (FDA) has yet to follow suit with a warning of its own, and the FDA-approved labels for these drugs do not carry a warning of this dangerous interaction.[3] However, we agree with Health Canada’s more protective approach.

What You Can Do

Do not take repaglinide-containing medications and clopidogrel together. If you are currently on both medicines, see your doctor immediately to discuss switching from repaglinide to another diabetes medication. Do not stop taking either drug before seeing your doctor.

To see Health Canada’s safety alert, visit the following link: http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/54454a-eng.php.

References

[1] Health Canada. Gluconorm (repaglinide) - New Contraindication for Concomitant Use with Clopidogrel. July 31, 2015. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2015/54454a-eng.php. Accessed August 19, 2015.

[2] Tornio A, Filppula AM, Kailari O, et al. Glucuronidation converts clopidogrel to a strong time-dependent inhibitor of CYP2C8: A phase II metabolite as a perpetrator of drug-drug interactions. Clin Pharmacol Ther. 2014;96(4):498-507.

[3] Drugs@FDA. Repaglinide label, updated March 2012. Clopidogrel label, updated July 2015. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed August 19, 2015.