Omeprazole inhibits the drug metabolizing enzyme (CYP2C19) which is responsible for the conversion of clopidogrel into its active form. The new studies compared the amount of clopidogrel’s active metabolite in the blood and its effect on platelets (anti-clotting effect) in people who took clopidogrel plus omeprazole versus those who took clopidogrel alone. A reduction in active metabolite levels of about 45 percent was found in people who received clopidogrel with omeprazole compared to those taking clopidogrel alone, according to the release. The effect of clopidogrel on platelets was reduced by as much as 47 percent in people receiving clopidogrel and omeprazole together. These reductions were seen whether the drugs were given at the same time or 12 hours apart.
The FDA is aware of studies that that might provide information about the effect of this interaction on clinical outcome, but study design and follow-up limit the applicability of study data to date. Therefore, based on the current scientific information, the clopidogrel label has been updated with new warnings on omeprazole and other drugs that inhibit the CYP2C19 enzyme that could interact with clopidogrel in the same way, according to the report. In addition, the manufacturer of Plavix (clopidogrel) is conducting follow-up studies to explore this and other drug interactions.
The FDA also released the following consideration for healthcare professionals regarding the Plavix/Prilosec interaction:
- 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.
- 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. Healthcare 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 and antacids are available OTC to relieve heartburn.
- Talk with your patients about the OTC medicines they take. Be aware that patients may be taking non prescription forms omeprazole and cimetidine.
Read the FDA’s release on the Plavix/Prilosec drug interaction.
