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All proton pump inhibitors except for rabeprazole and pantoprazole are metabolized by the hepatic CYP450 enzyme and therefore, may interact with the metabolism of clopidogrel. Omeprazole is considered to have higher potential for drug-drug interaction than other protein pump inhibitors because it is a CYP2C19 inhibitor. [17]
Pantoprazole, sold under the brand name Protonix, among others, is a medication used for the treatment of stomach ulcers, short-term treatment of erosive esophagitis due to gastroesophageal reflux disease (GERD), maintenance of healing of erosive esophagitis, and pathological hypersecretory conditions including Zollinger–Ellison syndrome.
Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. [10] It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent (dual antiplatelet therapy). [10] It is taken by mouth. [10]
[55] [57] An interaction between PPIs and the metabolism of the platelet inhibitor clopidogrel is known and this drug is also often used in people with cardiac disease. [58] [59] [22] There are associations with an increased risk of stroke, but this appears to be more likely to occur in people who already have an elevated risk. [60]
[3] [4] CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, [5] most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam. [6]
Due to drug-drug interactions, patients taking clopidogrel, an antiplatelet drug, should not take PPI except rabeprazole. [72] Since PPI changes the acidity of the gastric content, patients taking ketoconazole, atazanavir, iron, erlotinib, and MMF should not take PPI at the same time. [72] [73]
"Indiana University Department of Medicine Clinical Pharmacology Drug Interactions Flockhart Table ™". "INHIBITORS, INDUCERS AND SUBSTRATES OF CYTOCHROME P450 ISOZYMES". "The Life Raft Group: Long List of Inhibitors and Inducers of CYP3A4 and CYP2D6". "DRUGBANK Online: Cytochrome P-450 Enzyme Inhibitors".
Important drug interactions are rare. [38] [39] However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole. [40] Although still controversial, [41] this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.