title: Proton-pump inhibitors in patients requiring antiplatelet therapy: new FDA labeling.
abstract: Proton-pump inhibitors (PPIs) are recommended for patients who require antiplatelet therapy and have a history of upper gastrointestinal bleeding. Proton-pump inhibitors should also be considered for patients receiving antiplatelet therapy who have other risk factors for gastrointestinal bleeding, including use of aspirin. Thus, evidence of pharmacokinetic and pharmacodynamic interactions between PPIs and consequent impaired effectiveness of the antiplatelet agent clopidogrel has caused concern. Here, we discuss comparative studies suggesting that the extent to which a PPI reduces exposure to the active metabolite of clopidogrel and attenuates its antithrombotic effect differs among PPIs. Although a clinically meaningful effect of the interaction between PPIs and clopidogrel on cardiovascular outcomes has not been established, these studies provided the basis for recent changes in US Food and Drug Administration (FDA) labeling for several PPIs and clopidogrel. New labeling suggests that PPI use among patients taking clopidogrel be limited to pantoprazole, rabeprazole, lansoprazole, or dexlansoprazole. Because comparative studies indicate that omeprazole and esomeprazole have a greater effect on the CYP2C19-mediated conversion of clopidogrel to its active metabolite and, consequently, clopidogrel's effect on platelet reactivity, FDA labeling recommends avoiding omeprazole and esomeprazole in patients taking clopidogrel. Even a 12-hour separation of dosing does not appear to prevent drug interactions between omeprazole and clopidogrel.
authors.affiliation: Chief of Gastroenterology, Professor of Medicine, Division of Gastroenterology, Eastern Virginia Medical School, Norfolk, VA. Dajevms@aol.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Johnson
authors.forename: Robert
authors.initials: R
authors.lastname: Chilton
authors.forename: Harley R
authors.initials: HR
authors.lastname: Liker
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects; D001241:Aspirin / Q000009:adverse effects / Q000493:pharmacokinetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004336:Drug Antagonism; D004348:Drug Labeling; D004359:Drug Therapy, Combination; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology*; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin