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.

ACTION PLAN

• 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-http://www.bnf.org/).
• 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!)
Pharmacokinetics
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 Medicines.org but as at the time of publishing, the SPC version on the site is yet to be updated (http://emc.medicines.org.uk/document.aspx?documentId=9484)

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