Volume 190 - Issue 11
Risks of proton-pump inhibitors: what every doctor should know
Authors: Francisco J Fernández-Fernández, Gonzalo Pía and Pascual Sesma
Med J Aust 2009; 190 (11): 652-653. || doi: 10.5694/j.1326-5377.2009.tb02605.x
Published online: 1 June 2009
Published online: 1 June 2009
To the Editor: We read with interest Talley’s excellent and informative editorial about the risks associated with proton-pump inhibitors (PPIs).1 Other possible serious side effects of PPIs that need to be taken into account are potential drug interactions with aspirin and clopidogrel.
Aspirin is a weak acid that crosses the mucosa in its lipid state. The suppression of acid production reduces the lipophilic nature of this drug and, theoretically, might reduce its absorption and bioavailability.2 On the other hand, clopidogrel is a prodrug that is converted in the liver to an active metabolite. This bioactivation is mediated by hepatic cytochrome P450 isoenzymes,3 with cytochrome P450 2C19 (CYP2C19) playing a particularly important role. There is evidence suggesting that some PPIs (omeprazole, lansoprazole and rabeprazole) can inhibit CYP2C19, which would alter the effectiveness of clopidogrel and potentially lead to an increased risk of adverse cardiovascular outcomes.
In a recent Canadian case–control study among patients prescribed clopidogrel after acute myocardial infarction, current use of PPIs was associated with an increased risk of reinfarction (adjusted odds ratio, 1.27; 95% CI, 1.03–1.57).4 The risk was limited to patients currently taking a PPI (the authors did not find any association with more distant exposure to PPIs), and did not extend to pantoprazole, a drug that does not interfere with the conversion of clopidogrel to its active form.
References
- Talley NJ. Risks of proton-pump inhibitors: what every doctor should know [editorial]. Med J Aust 2009; 190: 109-110.
- Fernández-Fernández FJ. Might proton pump inhibitors prevent the antiplatelet effects of low- or very low-dose aspirin [letter]? Arch Intern Med 2002; 162: 2248. 0_i1091841
- Kim KA, Park PW, Hong SJ, Park JY. The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Clin Pharmacol Ther 2008; 84: 236-242. 0_i1091845
- Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009 Jan 28. [Epub ahead of print]. 0_BABGEGCF