title: [Interaction between clopidogrel and proton pump inhibitors].
abstract: The drug interaction between proton pump inhibitors and clopidogrel has been the subject of much study in recent years. Contradictory results regarding the effect of proton pump inhibitors on platelet reactivity and on clinical outcome in clopidogrel-treated patients have been reported in literature. Concomitant use of omeprazole and clopidogrel was found to decrease the exposure (AUC) to clopidogrel's active metabolite by 50% and to sharply increase platelet reactivity, as a result of inhibition by omeprazole of CYP2C19, a cytochrome P450 (CYP) enzyme. Pantoprazole has a much weaker effect on clopidogrel's pharmacokinetics and on platelet reactivity during concomitant use. The influence of the other proton pump inhibitors when used simultaneously with clopidogrel has not yet been investigated in adequately randomized studies. Regulatory agencies state that the combination of clopidogrel and the CYP2C19 inhibitors omeprazole and esomeprazole should be avoided. To date, there is no conclusive evidence of a clinically-relevant interaction between any of the proton pump inhibitors and clopidogrel.
authors.affiliation: St. Antonius Ziekenhuis, afd. Klinische Farmacie, Nieuwegein, the Netherlands. ankie.harmsze@cze.nl
authors.forename: Ankie M
authors.initials: AM
authors.lastname: Harmsze
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Henk
authors.initials: H
authors.lastname: Boot
authors.forename: Vera H M
authors.initials: VH
authors.lastname: Deneer
authors.forename: Mette
authors.initials: M
authors.lastname: Heringa
authors.forename: Peter G M
authors.initials: PG
authors.lastname: Mol
authors.forename: Tom
authors.initials: T
authors.lastname: Schalekamp
authors.forename: Monique M
authors.initials: MM
authors.lastname: Verduijn
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Marianne
authors.initials: M
authors.lastname: le Comte
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D000077144:Clopidogrel; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D064098:Esomeprazole; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D006801:Humans; D009853:Omeprazole / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000077144:Clopidogrel; D009853:Omeprazole; D064098:Esomeprazole; D013988:Ticlopidine