Volume 190 - Issue 11
Risks of proton-pump inhibitors: what every doctor should know
Authors: Nicholas J Talley, Aneta Dimoska and Kevin Gan
Med J Aust 2009; 190 (11): 652-653. || doi: 10.5694/j.1326-5377.2009.tb02607.x
Published online: 1 June 2009
Published online: 1 June 2009
In reply: Proton-pump inhibitors (PPIs) are often coprescribed for patients taking aspirin and clopidogrel to reduce gastrointestinal bleeding. There are emerging data that omeprazole diminishes the therapeutic effect of clopidogrel because the active enzyme in the liver, cytochrome P450 2C19 (CYP2C19), metabolises omeprazole and activates clopidogrel.1,2 In a large cohort study of 8205 patients with acute coronary syndrome and taking clopidogrel, 64% were also taking a PPI (60% omeprazole); 21% of those who were taking clopidogrel but no PPI died or were rehospitalised for acute coronary syndrome, versus 30% of those taking clopidogrel as well as a PPI.3 Notably, not all the PPIs have the same metabolic pathway. For example, omeprazole and esomeprazole are principally metabolised by CYP2C19 in contrast to lansoprazole, which is metabolised by cytochrome P450 3A4 (CYP3A4), and pantoprazole, which is metabolised by CYP2C19 O-demethylation then rapid sulfate conjugation. Thus, the negative interaction with clopidogrel may not apply to all PPIs (and pantoprazole may be the drug of choice if a PPI is required, as cytochrome P450 interactions are least likely).1 However, until more data are accumulated, all PPIs should probably be avoided where possible in patients who have been prescribed clopidogrel, unless there is no alternative.
It is correct that hyponatraemia has, rarely, been reported in patients taking PPIs. However, this knowledge is based solely on case report data, and therefore the level of evidence for cause and effect is relatively weak.
References
- Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole in the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA [Omeprazole Clopidogrel Aspirin] study. J Am Coll Cardiol 2008; 51: 256-260.
- Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009; 157: 148e1-148e5. 0_pgfId-1738628
- Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937-944. 0_pgfId-1738717