The Food and Drug Administration (FDA) is alerting the public and healthcare providers to new safety information concerning an interaction between clopidogrel (Plavix®), an anticlotting medication, and omeprazole (Prilosec™/Prilosec OTC™), a proton pump inhibitor (PPI) used to reduce stomach acid. New studies suggest that when the two medications are taken together, the effectiveness of clopidogrel is reduced. Patients at risk for heart attacks or strokes who use clopidogrel to prevent blood clots will not get the full effect of this medicine if they are also taking omeprazole and separating the two doses by up to 12 hours will not mediate the effect. The updated label for clopidogrel will contain details of the new studies submitted by Sanofi-Aventis and Bristol-Myers Squibb, the manufacturer of clopidogrel.
Omeprazole inhibits the drug-metabolizing enzyme (CYP2C19), which is responsible for the conversion of clopidogrel into its active metabolite. Individuals who took clopidogrel with omeprazole had a 45% reduction in active metabolite levels compared with those who took clopidogrel alone. Patients who took both drugs had a 47% reduction in clotting activity, whether the drugs were given concomitantly or up to 12 hours apart. There is no evidence that the H2 blockers ranitidine (Zantac) and famotidine (Pepcid) interfere with the anticlotting activity of clopidogrel.
Other drugs that should be avoided in combination with clopidogrel because of a similar interaction include: esomeprazole (Nexium®), cimetidine (Tagamet®/Tagamet HTB®), fluconazole (Diflucan®), ketoconazole (Nizoral®), voriconazole (VFEND®), etravirine (IntelenceTM), felbamate (Felbatol®), fluoxetine (Prozac® and Symbyax®), fluvoxamine (Luvox®), and ticlopidine (Ticlid®). The clopidogrel label has been updated with new warnings for possible interactions with these drugs.
At this time, the FDA does not have sufficient information concerning drug interactions between clopidogrel and PPIs other than omeprazole and esomeprazole to make specific recommendations regarding their coadministration. The FDA will continue to investigate other drug interactions with clopidogrel. The FDA plans to present this issue at the next meeting of the FDA’s Drug Safety Oversight Board in November. The Agency will communicate any further recommendations or conclusions once additional information is available.