Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

Andersson, Tommy; Nagy, Péter; Niazi, Mohammad; Nylander, Sven; Galbraith, Hal; Ranjan, Santosh; Wallentin, Lars

doi:10.1007/s40256-014-0073-4

Cited by 12 publications

(11 citation statements)

References 45 publications

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“…Omeprazoleis is associated with 30% and 10% reductions in the systemic clearance of diazepam and phenytoin, and even 50% or more with ketoconazole and atazanavir [96]. Recently, large-scale clinical trials were conducted on drug-drug interactions between PPIs and clopidogrel [97–99]. PPIs are mainly metabolized by hepatic microsomal enzymes, such as CYP2C19 and CYP3A4, and even have inhibitory effects on them, so care must be taken when combining drugs with PPIs.…”

Section: Discussionmentioning

confidence: 99%

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

et al. 2017

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Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

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Section: Discussionmentioning

confidence: 99%

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

et al. 2017

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“…First, we are unaware of a mechanism by which lansoprazole alone would exert this effect. Second, the complete nullification of clopidogrel’s pharmacodynamic effect by lansoprazole alone seems implausible, especially since PPIs have modest effects on adenosine diphosphate-induced platelet aggregation 48,49 and aggregation inhibition is likely less for lansoprazole vs. other PPIs. 50 Third, this subgroup analysis was not based on an a priori hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Comparative Risk of Ischemic Stroke Among Users of Clopidogrel Together With Individual Proton Pump Inhibitors

Leonard

Bilker

Brensinger

et al. 2015

Stroke

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Background and Purpose There is controversy and little information concerning whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We therefore aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999–2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole and pantoprazole—with pantoprazole serving as the referent. The endpoint was hospitalization for acute ischemic stroke, defined by International Classification of Diseases 9th Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results Among 325,559 concomitant users of clopidogrel and a PPI, we identified 1,667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval: 2.3–2.5). Adjusted hazard ratios for ischemic stroke vs. pantoprazole were: 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared to pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel.

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“…Therefore, it is reasonable to associate potential loss of clinical effectiveness in instances that result in significant decrease in exposure to active metabolite and antiplatelet activity. Co‐administration of omeprazole and esomeprazole clearly resulted in a significant reduction in the exposure to the active metabolite, thus warranting recommendations to avoid use of these medications with clopidogrel …”

Section: Use With Proton Pump Inhibitorsmentioning

confidence: 99%

“…Co-administration of omeprazole and esomeprazole clearly resulted in a significant reduction in the exposure to the active metabolite, thus warranting recommendations to avoid use of these medications with clopidogrel. 3,20,36 The recommendation to avoid concomitant use with clopidogrel does not apply to all members of the 'proton pump inhibitor' class, because the impact of this interaction is relatively less severe with other studied proton pump inhibitors-pantoprazole, lansoprazole, or dexlansoprazole. 20,37 A significant interaction for omeprazole or esomeprazole could likely be due to mechanistic differences in the nature of CYP2C19 inhibition compared to other proton pump inhibitors.…”

Section: Use With Proton Pump Inhibitorsmentioning

confidence: 99%

Clopidogrel, CYP2C19 and proton pump inhibitors: What we know and what it means

Hariharan

Southworth

Madabushi

2014

The Journal of Clinical Pharma

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Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers

Cited by 12 publications

References 45 publications

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

Comparative Risk of Ischemic Stroke Among Users of Clopidogrel Together With Individual Proton Pump Inhibitors

Clopidogrel, CYP2C19 and proton pump inhibitors: What we know and what it means

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