News Brief for October 2017

FDA Grants Public Citizen Petition, Requires New Warnings About Dangerous Drug Interaction

Acting with unusual speed, the Food and Drug Administration (FDA) on Aug. 7 partially granted[1] a Dec. 28, 2016, petition[2] from Public Citizen’s Health Research Group. The petition had asked the agency to immediately require that the product labeling for repaglinide-containing medications (PRANDIN, PRANDIMET) be revised to include a warning about the risk of dangerously low blood sugar levels when these drugs and clopidogrel (PLAVIX) are taken together.

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.

The basis for Public Citizen’s petition was data from a study conducted in nine healthy subjects who were given repaglinide with and without clopidogrel over separate three-day periods.[3] Clopidogrel increased the concentration of repaglinide in the blood to levels that were four to five times higher than those that occurred when repaglinide was given alone. This resulted in a significant drop in blood sugar levels.

The FDA granted our request to include information about this dangerous interaction with clopidogrel on the labeling for repaglinide-containing products. However, the agency denied our additional request to include on the labels for these drugs a statement that they should not be used together under any circumstances, an action that Health Canada, an agency similar to the FDA, wisely took in 2015.

Refernces

[1] Food and Drug Administration. Letter to Public Citizen regarding citizen petition FDA-2016-P-4584. https://www.regulations.gov/document?D=FDA-2016-P-4584-0012. Accessed August 29, 2017.

[2] Public Citizen. Petition to the FDA to require a warning about a dangerous drug interaction between clopidogrel (Plavix) and repaglinide (Prandin) in the label for both drugs. December 21, 2016. https://www.citizen.org/our-work/health-and-safety/petition-fda-require-warning-about-dangerous-drug-interaction-between-clopidogrel-plavix-and. Accessed August 29, 2017.

[3] 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.