What are the interactions between omeprazole and Plavix (clopidogrel)?

From the Guidelines

Taking omeprazole and Plavix (clopidogrel) together is generally not recommended due to a potentially significant drug interaction, as omeprazole can reduce the effectiveness of Plavix by inhibiting the enzyme CYP2C19, which is needed to convert Plavix into its active form 1. This interaction may increase your risk of cardiovascular events like heart attack or stroke if you're taking Plavix for heart protection. Some key points to consider when taking these medications together include:

• The risk of gastrointestinal bleeding, especially in patients at increased risk, such as the elderly, those with a history of GI bleeding or peptic disease, high alcohol consumption, chronic use of steroids or non-steroidal anti-inflammatory drugs (NSAIDs), or receiving a combination of antithrombotic drugs 1.
• The use of proton pump inhibitors, such as omeprazole, may be effective in reducing the risk of GI bleeding, but their use is discouraged in combination with clopidogrel due to the potential interaction 1.
• Alternative medications, such as pantoprazole or famotidine, may be safer options to use with Plavix as they have less impact on CYP2C19. Some important considerations when making decisions about taking these medications together include:
• Weighing the individual risks of stomach bleeding against cardiovascular protection 1.
• Considering the patient's overall risk factors for GI bleeding and cardiovascular events 1.
• Discussing alternative medications and treatment options with a healthcare provider 1. Never stop either medication without consulting your doctor first, and if you're currently taking both medications, contact your healthcare provider promptly to discuss alternatives.

From the FDA Drug Label

In a crossover clinical study, 72 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with omeprazole (80 mg at the same time as clopidogrel) for 5 days The exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5) when clopidogrel and omeprazole were administered together.

Results from another crossover study in healthy subjects showed a similar pharmacokinetic interaction between clopidogrel (300 mg loading dose/75 mg daily maintenance dose) and omeprazole 80 mg daily when co-administered for 30 days Exposure to the active metabolite of clopidogrel was reduced by 41% to 46% over this time period

In another study, 72 healthy subjects were given the same doses of clopidogrel and 80 mg omeprazole but the drugs were administered 12 hours apart; the results were similar, indicating that administering clopidogrel and omeprazole at different times does not prevent their interaction [see Warnings and Precautions (5. 6), Drug Interactions (7)].

Avoid concomitant use of omeprazole with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart.

Taking omeprazole and Plavix (clopidogrel) together is not recommended because omeprazole can decrease the exposure to the active metabolite of clopidogrel by 41% to 46%, which may reduce the effectiveness of clopidogrel in preventing blood clots.

• Alternative anti-platelet therapy should be considered when using omeprazole.
• The reduction in clopidogrel's active metabolite occurs even when the two drugs are administered 12 hours apart. 2

From the Research

Interaction between Omeprazole and Clopidogrel

• The use of omeprazole with clopidogrel has been shown to reduce the antiplatelet effect of clopidogrel 3, 4, 5, 6.
• Studies have found that omeprazole inhibits the bioactivation of clopidogrel to its active metabolite, leading to decreased efficacy of clopidogrel 4, 5, 6.
• The reduction in clopidogrel's effect when used with omeprazole has been associated with an increased risk of ischemic stroke 4 and other cardiac adverse outcomes 7.

Comparison with Other Proton Pump Inhibitors

• Not all proton pump inhibitors (PPIs) have the same effect on clopidogrel's efficacy, with pantoprazole showing no significant interaction with clopidogrel 6.
• Ranitidine, a histamine receptor type 2 (H2) blocker, has also been shown to have no effect on the antiplatelet function of clopidogrel 3, 5.

Clinical Implications

• The use of omeprazole with clopidogrel requires careful consideration of the potential risks and benefits, particularly in patients at high risk of cardiac adverse outcomes 7.
• Alternative PPIs, such as pantoprazole, or H2 blockers, such as ranitidine, may be considered for patients requiring dual antiplatelet therapy 6, 7.