Clopidogrel and Proton Pump Inhibitors

We have just receive some indication from the manufacturers (Sanofi Aventis + Bristol-Myer Squibb ) that Clopidogrel-containing medicines and proton pump inhibitors (PPIs) ‘should be avoided unless absolutely necessary’. The preliminary studies indicate a cytochrome P450-type interaction.

Clopidogrel is a pro-drug which is metabolised in the liver, partially by the cytochrome P450 complex. Hence any medication which inhibits these liver enzymes has a potential to reduce the efficacy of clopidogrel.

Clopidogrel indicated in adults for the prevention of atherothrombotic events in:

  • Patients suffering from myocardial infarction, Ischaemic stroke or established peripheral arterial disease
  • Patients suffering from acute coronary syndrome

In both cases, the reduction of efficacy is not only undesirable but may result in serious consequences.


  • Consider alternatives to PPI in patients – e.g. H2 blockers or antacids.
  • Consider alternatives to other cytochrome complex inhibitors such as Fluvoxamine, Moclobemide, Fluconazole, Ciprofloxacin, Cimetidine etc (refer to the BNF-
  • Community pharmacists to systematically identify affected patients and act accordingly with consultation with their GPs

A little bit more (for those who just want to know!)
Absorption: Mean peak plasma level occurs ~ 45min after dosing
Distribution: Highly protein bound (Clopidogrel: 98%; Inactive metabolite 94%) – Reversible.
Metabolism: Extensive metabolism in liver with 85% of circulating metabolites mediated by cytochomes P450
Elimination: Half life after a single oral dose of clopidogrel 6 hours. Elimination half-life of the main circulating (inactive) metabolite was 8 hours after a single administration.

We would recommend that you review the SPC on but as at the time of publishing, the SPC version on the site is yet to be updated (

Nevertheless, if you have further queries about this, please contact Sanofi-aventis (number in the usual places.)

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