Safety Corner: News You Need to Know

Drug Interaction: Clopidogrel and Omeprazole Interaction

According to rxlist clopidogrel (Plavix) is one of the top 15 prescriptions filled in the United States. Clopidogrel is an antiplatelet agent that is prescribed to inhibit blood clots. Omeprazole (Prilosec or Prilosec OTC) is a commonly used prescription and OTC product for gastric acid suppression. Both agents have been available in the United States for many years and with omeprazole being an OTC product, the combined use of these two agents is not accurately known.

In the fall of 2009, the U.S. Food and Drug Administration (FDA) alerted the healthcare community and the public of a significant drug interaction between clopidogrel and omeprazole. When taken together, the combination of these two drugs can decrease clopidogrel's effectiveness. The ability for clopidogrel to prevent clotting is decreased and patients who are taking the drug to prevent a heart attack or stroke will not receive the full effects. The studies completed by the manufacturers of clopidogrel showed a 47 percent decrease in the effectiveness of the drug to inhibit platelets when taken with omeprazole.

The interaction is driven by omeprazole's inhibition of the CYP2C19 enzyme in the body. Other medications are also potent inhibitors of this enzyme and can cause a decrease in clopidogrel's action as well. Other examples are: cimetidine, fluconazole, ketoconazole, voriconazole, etravirine, felbamate, fluoxetine, fluvoxamine, esomeprazole, and ticlopidine. It is not known to what extent other PPIs, other than esomeprazole, inhibit CYP2C19.

Due to this information, the FDA provided the following recommendations to healthcare providers:

• The concomitant use of omeprazole and clopidogrel should be avoided because of the effect on clopidogrel's active metabolite levels and anti-clotting activity. Patients at risk for heart attacks or strokes, who are given clopidogrel to prevent blood clots, may not get the full protective anti-clotting effect if they also take prescription omeprazole or the OTC form (Prilosec OTC).
• Separating the dose of clopidogrel and omeprazole in time will not reduce this drug interaction.
• Other drugs that should be avoided in combination with clopidogrel because they may have a similar interaction include: esomeprazole (Nexium), cimetidine (which is available by prescription Tagamet and OTC as Tagamet HB), fluconazole (Diflucan), ketoconazole (Nizoral), voriconazole (VFEND), etravirine (Intelence), felbamate (Felbatol), fluoxetine (Prozac, Serafem, Symbyax), fluvoxamine (Luvox), and ticlopidine (Ticlid).
• At this time FDA does not have sufficient information about drug interactions between clopidogrel and PPIs other than omeprazole and esomeprazole to make specific recommendations about their co-administration. Health care professionals and patients should consider all treatment options carefully before beginning therapy.
• There is no evidence that other drugs that reduce stomach acid, such as most H2 blockers ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid), except cimetidine (Tagamet and Tagamet HB, a CYP2C19 inhibitor) or antacids interfere with the anti-clotting activity of clopidogrel. Ranitidine and famotidine are available by prescription and OTC to relieve and prevent heartburn. Antacids are available OTC to relieve heartburn.

Further information on this interaction is available through the FDA website.

View the rxlist Top 200 Drugs List by Prescription.