Clopidogrel/Esomeprazole; Omeprazole; Cimetidine
This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.
Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
How the interaction occurs:
Some proton pump inhibitors and cimetidine may slow down how quickly your liver processes clopidogrel to its active form.
What might happen:
Your clopidogrel may not work as well or at all.
What you should do about this interaction:
Make sure your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. Your doctor may want to change your proton pump inhibitor or cimetidine to a different medicine.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.
1.Plavix (clopidogrel bisulfate) US prescribing information. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership December, 2013.
2.Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, Kurihara A. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 2010 Jan; 38(1):92-9.
3.Ogilvie BW, Yerino P, Kazmi F, Buckley DB, Rostami-Hodjegan A, Paris BL, Toren P, Parkinson A. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel. Drug Metab Dispos 2011 Nov;39(11):2020-33.
4.US Food and Drug Association. Information on Clopidogrel Bisulfate (marketed as Plavix). Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPati entsandProviders/ucm190836.htm October 27, 2010.
5.Gilard M, Arnaud B, Cornily JC, Le Gal G, Lacut K, Le Calvez G, Mansourati J, Mottier D, Abgrall JF, Boschat J. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol 2008 Jan 22;51(3):256-60.
6.Yun KH, Rhee SJ, Park HY, Yoo NJ, Kim NH, Oh SK, Jeong JW. Effects of omeprazole on the antiplatelet activity of clopidogrel. Int Heart J 2010 Jan;51(1):13-6.
7.Siller-Matula JM, Spiel AO, Lang IM, Kreiner G, Christ G, Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J 2009 Jan;157(1):148.e1-5.
8.Sibbing D, Morath T, Stegherr J, Braun S, Vogt W, Hadamitzky M, Schomig A, Kastrati A, von Beckerath N. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009 Apr;101(4):714-9.
9.Cuisset T, Frere C, Quilici J, Poyet R, Gaborit B, Bali L, Brissy O, Morange PE, Alessi MC, Bonnet JL. Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J Am Coll Cardiol 2009 Sep 22;54(13):1149-53.
10.Zuern CS, Geisler T, Lutilsky N, Winter S, Schwab M, Gawaz M. Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy. Thromb Res 2010 Feb;125(2):e51-4.
11.Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, Shook TL, Lapuerta P, Goldsmith MA, Laine L, Scirica BM, Murphy SA, Cannon CP. Clopidogrel with or without Omeprazole in Coronary Artery Disease. N Engl J Med 2010 Oct 6.
12.Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O, Bergougnan L, Perrin L, Lacreta FP, Hurbin F, Dubar M. Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled, Crossover Comparison Studies. Clin Pharmacol Ther 2010 Sep 15.
13.Ferreiro JL, Ueno M, Capodanno D, Desai B, Dharmashankar K, Darlington A, Charlton RK, Bass TA, Angiolillo DJ. Pharmacodynamic effects of concomitant versus staggered clopidogrel and omeprazole intake: results of a prospective randomized crossover study. Circ Cardiovasc Interv 2010 Oct 1;3(5):436-41.
14.Siriswangvat S, Sansanayudh N, Nathisuwan S, Panomvana D. Comparison between the effect of omeprazole and rabeprazole on the antiplatelet action of clopidogrel. Circ J 2010 Oct;74(10):2187-92.
15.Furuta T, Iwaki T, Umemura K. Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes. Br J Clin Pharmacol 2010 Sep;70(3):383-92.
16.Aubert RE, Epstein RS, Teagarden JR, Xia F, Yao J, Desta Z, Skaar T, Flockhart DA. Abstract 3998: Proton pump inhibitiors effect on clopidogrel effectiveness: the clopidogrel Medco outcomes study. Circulation 2008;118:S815.
17.Kreutz RP, Stanek EJ, Aubert R, Yao J, Breall JA, Desta Z, Skaar TC, Teagarden JR, Frueh FW, Epstein RS, Flockhart DA. Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel medco outcomes study. Pharmacotherapy 2010 Aug;30(8):787-96.
18.Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Available at: http://www.cmaj.ca/cgi/rapidpdf/cmaj.082001. CMAJ March 31, 2009; 180(7):online 1-7.
19.Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009 Mar 4;301(9):937-44.
20.Stockl KM, Le L, Zakharyan A, Harada AS, Solow BK, Addiego JE, Ramsey S. Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor. Arch Intern Med 2010 Apr 26;170(8):704-10.
21.Gaglia MA Jr, Torguson R, Hanna N, Gonzalez MA, Collins SD, Syed AI, Ben-Dor I, Maluenda G, Delhaye C, Wakabayashi K, Xue Z, Suddath WO, Kent KM, Satler LF, Pichard AD, Waksman R. Relation of proton pump inhibitor use after percutaneous coronary intervention with drug-eluting stents to outcomes. Am J Cardiol 2010 Mar 15;105(6):833-8.
22.Zairis MN, Tsiaousis GZ, Patsourakos NG, Georgilas AT, Kontos CF, Adamopoulou EN, Vogiatzidis K, Argyrakis SK, Fakiolas CN, Foussas SG. The impact of treatment with omeprazole on the effectiveness of clopidogrel drug therapy during the first year after successful coronary stenting. Can J Cardiol 2010 Feb;26(2):e54-7.
23.O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y, Michelson AD, Hautvast RW, Ver Lee PN, Close SL, Shen L, Mega JL, Sabatine MS, Wiviott SD. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet 2009 Sep 19;374(9694):989-97.
24.Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K, Daugherty JR, Kaltenbach LA, Stein CM. Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med 2010 Mar 16; 152(6):337-45.
25.Prilosec (omeprazole) US prescribing information. AstraZeneca Pharmaceuticals LP March, 2014.
26.Nexium (esomeprazole magnesium) US prescribing information. AstraZeneca Pharmaceuticals LP March, 2014.
27.Aciphex (rabeprazole) prescribing information. Eisai Inc. April 19, 2013.