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[55] [56] PPIs are commonly used in people with cardiovascular disease for gastric protection when aspirin is given for its antiplatelet actions. [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.
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]
The CYP2C19 enzyme metabolizes proton pump inhibitors (PPI) as well as clopidogrel. Various reports have stated that there is a negative clopidogrel-omeprazole drug interaction. Some studies have found that clopidogrel activity on platelets was hampered significantly by patients receiving treatment with omeprazole, a proton pump inhibitor (PPI).
[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]
[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.
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]
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and the hydrophobic effect. Many are physical contacts with molecular associations between chains that ...
Targeted covalent inhibitors (TCIs) or Targeted covalent drugs are rationally designed inhibitors that bind and then bond to their target proteins.These inhibitors possess a bond-forming functional group of low chemical reactivity that, following binding to the target protein, is positioned to react rapidly with a proximate nucleophilic residue at the target site to form a bond.