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pantoprazole oral

Clopidogrel/Selected Proton Pump Inhibitors

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.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Some proton pump inhibitors may slow down how quickly your liver processes clopidogrel to its active form.

What might happen:

Your clopidogrel may not work as well.

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 to a different proton pump inhibitor or 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.

References:

1.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.
2.Plavix (clopidogrel bisulfate) US prescribing information. Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership December, 2011.
3.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.
4.Luria X. Public Statement: Interaction between clopidogrel and proton-pump inhibitors. CHMP updates warning for clopidogrel-containing medicines. European Medicines Agency. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2010 /03/WC500076346.pdf March 17, 2010.
5.Jacobs LD, Shulman HM. Dear Canadian Healthcare Professional: Subject: Potential interaction of Proton Pump Inhibitors (PPIs) with Plavix (clopidogrel). Sanofi-Aventis Canada Inc. and Bristol Myers Squibb Canada Co. August 14, 2009.
6.Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D. Steg PG, Trenk D. Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 2010 Oct 27;304(16):1821-30.
7.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.
8.Protonix (pantoprazole sodium) US prescribing information. Wyeth Pharmaceuticals, Inc. December, 2013.
9.Prevacid (lansoprazole) US prescribing information. Takeda Pharmaceuticals America, Inc. September, 2012.
10.Dexilant (dexlansoprazole) US prescribing information. Takeda Pharmaceuticals North America, Inc. September, 2012.
11.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.
12.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.
13.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.
14.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.
15.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.
16.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.
17.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.
18.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.
19.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.
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.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.
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.Aciphex (rabeprazole) prescribing information. Eisai Inc. April 19, 2013.

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