East Asian perspective on the interaction between proton pump inhibitors and clopidogrel

Abstract

Both proton pump inhibitors (PPIs) and clopidogrel are widely prescribed in the Asia-Pacific population. PPIs are the mainstay therapeutic agents for prophylaxis against aspirin gastropathy and for acid-related disorders including gastroesophageal reflux disease. They are also co-prescribed with oral anticoagulant agents and with dual-antiplatelet therapy for the treatment and prevention of gastrointestinal bleeding. Clopidogrel belongs to the drug class of thienopyridines and is currently the most widely prescribed oral anticoagulant agent either alone or in combination with aspirin. Platelet inhibition by clopidogrel is prone to significant inter-individual variability and is believed to be affected by several factors such as genetics and drug-drug interactions. Since it was first reported in 2009, the potential for drug-drug interactions between PPIs and clopidogrel has remained headline news, and its significance in clinical practice is the subject of an ongoing debate. For East Asian patients in particular, the clinical relevance of the interaction between PPIs and clopidogrel remains unclear because of conflicting data, as well as underrepresentation of East Asian subjects in landmark trials. Increased CYP2C19 genetic polymorphisms in individuals from Asia-Pacific countries only fuel the confusion. Recent studies in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. This review aims to help clinicians choose the most appropriate PPI for co-prescription with clopidogrel in patients from Asia-Pacific countries.

Proton pump inhibitor utilisation and potentially inappropriate prescribing analysis: insights from a single-centred retrospective study

“…15 Besides, similar increases in prescription rates have also been observed in many other countries. [16][17][18][19] Although our result revealed Open access that the prevalence of PPI use was less than that of other reports, an appreciable increase in PPI utilisation has been witnessed in other regions in China 20 which could be reflected in a study conducted, in particular, for injectable PPIs. 4 These facts pose serious queries and concerns on the inappropriate use of PPIs, the occurrence of potential side effects and the increase in healthcare costs.…”

“…In March 2010, The Food and Drug Administration (FDA) issued a 'black box warning' to warn that the prescription on clopidogrel should avoid concomitant use of omeprazole or esomeprazole if the patients have been identified as CYP2C19 poor metabolisers, 33 especially in East-Asian patients for whom the CYP2C19 loss-of-function (LoF) allele is associated with an increased risk of adverse cardiovascular outcomes when treated with clopidogrel. 19 In this case, lansoprazole and pantoprazole could be considered as a rational choice. 34 In terms of cost-effective prescribing, the DDC results showed that the highest average daily costs of PPIs were injectable omeprazole, followed by oral esomeprazole.…”

Risks of adverse events for users of proton‐pump inhibitors plus aspirin or clopidogrel in patients with aspirin‐related ulcer bleeding

“…23 Concomitantly administered pantoprazole or rabeprazole did not affect the pharmacokinetic and antiplatelet efficacy of clopidogrel because of the weaker affinity for the CYP2C19 isoenzyme. 24,25 Moreover, recent studies 26,27 in East Asian cohorts suggests that the potential of PPIs to attenuate the efficacy of clopidogrel could be minimized by the use of newer PPIs with weaker affinity for the CYP2C19 isoenzyme, namely, pantoprazole, dexlansoprazole, and rabeprazole. In our study, pantoprazole and lansoprazole were the two most commonly prescribed PPIs for acute UGIB.…”

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction

“…As PPI use increases worldwide, growing concerns about PPI complications have been raised [ 6 , 7 , 8 ]. Specifically, drug interaction with clopidogrel, which is an antiplatelet agent classified as thienopyridines, has been postulated in many recent studies [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Both PPIs and clopidogrel are metabolized by hepatic cytochrome P450 (CYP) enzymes; in the presence of CYP2C19 inhibition, PPIs could reduce the efficacy of clopidogrel’s protective roles in cardiovascular events [ 22 ].…”