Alerts
Clopidogrel Bisulfate (Plavix) - Potential Interactions with Omeprazole (Prilosec) and Esomeprazole (Nexium) - Ongoing Safety Review
November 19, 2010
In January 2009, the FDA informed health care professionals about an ongoing safety review of clopidogrel. The safety review began in response to published reports showing clopidogrel may be less effective in some patients, possibly due to genetic factors or drug interactions.
The safety review found that omeprazole decreases the effectiveness of clopidogrel by inhibiting CYP2C19 metabolism and reducing conversion of clopidogrel to its active form. Concentrations of clopidogrel’s active metabolite were reduced by up to 45% when given with omeprazole. This interaction occurs whether the medications are administered simultaneously or at different times. A similar interaction is expected with esomeprazole. Avoid concomitant therapy with clopidogrel and omeprazole or esomeprazole. The clopidogrel product labeling has been updated with this information.
It is unknown if this interaction occurs with other proton pump inhibitors (PPI), such as lansoprazole, pantoprazole, or rabeprazole. Clopidogrel manufacturers continue to work with the FDA to study the effect of genetics, other PPIs, and other drugs on clopidogrel efficacy. The results of these studies are expected to take several months to complete. There is no current evidence that acid-reducing drugs that do not inhibit CYP2C19 decrease the effectiveness of clopidogrel.
In November 2010, the American College of Cardiology, the American College of Gastroenterology, and American Heart Association issued a consensus statement recommending PPIs for patients who are taking clopidogrel and also have an increased risk of gastrointestinal (GI) bleeding. Patients with a high risk of GI bleeding include those with a prior history of GI bleed (highest risk), elderly patients, patients with a Helicobacter pylori infection, or concomitant use if anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), or steroids.
Continue prescribing clopidogrel to patients as appropriate. For patients who require acid reduction during clopidogrel therapy, FDA continues to recommend avoiding concomitant therapy with omeprazole or esomeprazole. Instead, consider therapy with an agent that does not inhibit CYP2C19, such as antacids, famotidine (Pepcid), nizatidine (Axid), or ranitidine (Zantac). Inform patients taking clopidogrel to continue taking clopidogrel as directed, and encourage them to discuss any concerns with their primary care provider. Other drugs that inhibit 2C19 should also be avoided with clopidogrel including cimetidine (Tagamet), etravirine (Intelence), felbamate (Felbatol), fluconazole (Diflucan), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), ketoconazole (Nizoral), ticlopidine (Ticlid), and voriconazole (Vfend).
Additional information is available at:
- ACCF/ACG/AHA 2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines
- FDA Medwatch Alerts:
- November 2009:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm190848.htm - January 2009:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/ SafetyAlertsforHumanMedicalProducts/ucm092066.htm - Information for HealthCare Professionals:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm190787.htm - Public Health Advisory:
http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm190825.htm - Updated clopidogrel (Plavix) product label:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf - Ongoing safety review:
- Follow-up:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm190784.htm - Early communication:
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm079520.htm
Updated
November 19, 2010; November 10, 2010; November 17, 2009; January 27, 2009; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.
