Concomitant Use of Clopidogrel and Proton-Pump Inhibitor
Concomitant Use of Clopidogrel and Proton-Pump Inhibitor
In terms of practical recommendations for prescribing clopidogrel and PPIs, it would be fair to say that the effect is, at best, modest; however, not trivial since it relates to death and MI. This issue has gained much traction as it does have a pharmacodynamic basis. In addition, the fact that PPIs are available over-the-counter, makes the true estimate of its effect on cardiovascular outcomes hard to assess in real time, along with increasing the potential for widespread uncontrolled use by patients, which make this an issue of great importance to resolve. Therefore, the evidence for the FDA position on the concomitant use of clopidogrel and PPI can be challenged, yet it is understandable from a public health policy perspective. Our primary recommendations for practitioners at this given time are first to avoid empiric use of PPIs with clopidogrel. Second, it might be logical to prefer pantoprazole to other PPIs. Although the FDA recommendation states that separating the dose of clopidogrel and omeprazole in time, will not reduce this drug interaction, we still advocate temporally separating the two drugs by advising patients to take them at least 4–6 h apart. This takes into consideration the mechanism of interaction (competitive interference in metabolism of clopidogrel) and the pharmacokinetics of both drugs as most PPIs have a short half-life (30 min–2 h). We believe that these common sense measures might minimize the risk of potential adverse interaction between clopidogrel and PPIs, until more conclusive evidence on this ongoing question are presented.
Recommendations
In terms of practical recommendations for prescribing clopidogrel and PPIs, it would be fair to say that the effect is, at best, modest; however, not trivial since it relates to death and MI. This issue has gained much traction as it does have a pharmacodynamic basis. In addition, the fact that PPIs are available over-the-counter, makes the true estimate of its effect on cardiovascular outcomes hard to assess in real time, along with increasing the potential for widespread uncontrolled use by patients, which make this an issue of great importance to resolve. Therefore, the evidence for the FDA position on the concomitant use of clopidogrel and PPI can be challenged, yet it is understandable from a public health policy perspective. Our primary recommendations for practitioners at this given time are first to avoid empiric use of PPIs with clopidogrel. Second, it might be logical to prefer pantoprazole to other PPIs. Although the FDA recommendation states that separating the dose of clopidogrel and omeprazole in time, will not reduce this drug interaction, we still advocate temporally separating the two drugs by advising patients to take them at least 4–6 h apart. This takes into consideration the mechanism of interaction (competitive interference in metabolism of clopidogrel) and the pharmacokinetics of both drugs as most PPIs have a short half-life (30 min–2 h). We believe that these common sense measures might minimize the risk of potential adverse interaction between clopidogrel and PPIs, until more conclusive evidence on this ongoing question are presented.
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