Advanced pharmacology
Proton pump inhibitors are a class of novel drugs that are the most potent acid suppressors on the market today. Since omeprazole’s introduction in 1990, they have been clinically proven to be better than H2RAs. Over the past decade their use has been scrutinized because of several harmful disease associations.C. difficile infection: FDA’s analysis of over 28 studies revealed that patients taking PPIs were at a 1.4-2.75 times greater risk of developing an infectionFractures: FDA reviewed several studies and have concluded that PPIs in high doses, multiple daily doses, and/or continued therapy for longer than a year increase a person’s risk of osteoporosis related fractureMagnesium: PPIs may decrease magnesium level, which can lead to muscle spasms, arrhythmias, seizures, and fatigue. This typically occurs after long-term administration of PPIs, usually longer than a year. Treatment may require magnesium replacement and PPI discontinuationDementia: Although several theories exist to possibly explain the mechanism, the association needs to be validated in large cohorts and tested in case-control studies. For now, it is probably safe to say a causal link is plausible.H. Pylori infection causes gastritis, PUD, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma and the association between the presence of H. pylori and NSAIDs and an increased incidence of PUD is well documented.How would you handle a patient who wants to begin long-term PPI use?What would your discussion with them entail?In what patients or disease states would you not recommend PPI use?What if H. Pylori is found to be present?The following FDA warning appears in the clopidogrel package insert: “Drug interactions: Co-administration of Plavix with omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of Plavix if given concomitantly or if given 12 hours apart. ” Plavix (clopidogrel) [package insert] Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership Bridgewater, NJ. 2009.Evidence-based guidelines such as those provided by the AGA state: “PPI therapy does not need to be altered in concomitant clopidogrel users as there does not appear to be an increased risk for adverse cardiovascular events”. (Strong recommendation, high level of evidence) Am J Gastroenterol 2013; 108:308–328; doi:10.1038/ajg.2012.444.This leaves the provider to make a professional decision.You may wish to read the portion of clopidogrel’s package insert [link below] regarding pharmacogenomics as well as the article found in Medscape [link below] regarding genetics in pharmacotherapy before answering the last question. Pharmacogenomics is, and will become, an increasingly bigger part of care as we move forward.https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdfhttps://www.medscape.com/viewarticle/888159_2After reviewing the package insert for clopidrogel and available evidence regarding this combination, what would you recommend if a patient is taking esomeprazole and clopidrogel together?