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Medication News & Update

Proton Pump Inhibitors and Plavix – Chemical Logic?

   Just a few months ago the news about an interaction between

omeprazole (Prilosec®) which prevented the conversion of the prodrug clopidogrel(Plavix®) to its active agent hit the press. Long before this we mentioned the potential

decrease in effectiveness of Plavix in combination with any drugs which

inhibit the liver enzyme pathways 3A and 2C. This includes lovastatin as well as PlavixThe initial study brought attention to this interaction and then controversy began. The controversy involved the fact that

the interaction was not clinically significant and indicated that the interaction was more prominent with omeprazole and less so with pantoprazole(Protonix®).   As of March 2010, the FDA has required

a black box warning on clopidogrel to this effect - to indicate that some patients do not metabolize the drug properly and may receive little benefit from it. The warning indicates that the drug is dangerous only in the sense that it doesn't work in those patients and thus may leave them unprotected against heart attacks and strokes. Studies have identified that clopidogrel – proton pump interactions were prominent in these slow metabolizers.

Another very recent study appearing in the Archives of Internal Medicine indicates that

A near doubling of re-hospitalizations for myocardial infarct occurred in patient receiving

the combination drug therapy. This study while small involving 1,000 patients who were on the combo therapy vs another 1,000 patients on clopidogrel alone. All patients had been hospitalized either with an MI or for placement of a coronary stent. Almost one year later the patients receiving the combination of clopidogrel and a proton pump inhibitor had approximately double the re-hospitalization for myocardial infarct or stent placement compared to those on clopidogrel alone.   The effect was not limited to omeprazole — increased re-hospitalizations were also seen among users of the PPI pantoprazole.

    While controversy over this issue remains the chemistry logically indicates otherwise.

This is especially true in the elderly population. One may also wish to question the effectiveness of clopidogrel with statins and other drugs which inhibit 3A anad 2C  hepatic enzyme pathways. Aspirin still remains the first line agent except in failed therapy with aspirin, asthmatic patients and acute coronary syndrome patients. It is the opinion of this reviewer that aspirin is  cheaper and as effective as Plavix alone and not subject to the above interaction.

Clarke TA, Waskell LA. The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin.

Drug Metabolism and Disposition 2003;31:53-9.

Therapeutic Research Center Pharmacist’s Letter / Prescriber’s Letter(Detail-Document #220233: Page 2 of 6)

Risk of Rehospitalization for Patients Using Clopidogrel With a Proton Pump Inhibitor Karen M. Stockl, PharmD; Lisa Le, MS; Armen Zakharyan, PhD; Ann S. M. Harada, PhD, MPH; Brian K. Solow, MD; Joseph E. Addiego, MD; Scott Ramsey, MD, PhD Arch Intern Med. 2010;170(8):704-710.