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Potintial interaction b/t PPIs and clopidogrel
Transcript of Potintial interaction b/t PPIs and clopidogrel
Clopidogrel is a thienopyridine, inhibiting adenosine diphosphate (ADP) induced platelet activation by blocking the P2Y12 receptor on the platelet surface. After ingestion of clopidogrel, the majority 85% of the prodrug is immediately inactivated by plasma esterases to an inactive from. Approximately 15% of an absorbed clopidogrel dose is converted to an active thiol metabolite; mainly by the hepatic cytochrome P450 isoenzymes and CYP2C19 playing a major role.
Dr. Fadwa Alkhuraisi
Clopidogrel -PPIs interaction:
In situations when both clopidogrel and a PPI are indicated, omeprazole, esomeprazole and lansoprazole should be avoided because they are the PPIs that are
to interact with clopidogrel but pantoprazole is
to interact with clopidogrel.
For that pantoprazole should be used with clopidogrel and Famotidine is the alternative.
Wide separation of PPIs and clopidogrel could minimize the potential clinical drug interactions.
1) Lauren B. Gerson. Proton Pump Inhibitors and Potential Interactions
with Clopidogrel. Curr Gastroenterol Rep. New York 2013. 15:329
2) Steven P. Dunn, Steven R. Steinhubl, Deborah Bauer, Richard J. Charnigo, Peter B. Berger and Eric J. Topol. Impact of Proton Pump Inhibitor Therapy on the Efficacy of Clopidogrel in the CAPRIE and CREDO Trials. J Am Heart Assoc. originally published January 15, 2013. 2:e004564
3) Shoa-Lin Lin, Hui-Min Chang, Chun-Peng Liu, Li-Ping Chou, Jaw-Wen Chan. Clinical evidence of interaction between clopidogrel and proton pump inhibitors. World J Cardiol 2011 May 26; 3(5): 53-164.
4) Michael D Drepper, Laurent Spahr, Jean Louis Frossard. Clopidogrel and proton pump inhibitors - where do we stand in 2012?. World J Gastroenterol 2012 May 14; 18(18): 2161-2171.
5) lexicomp and micromedex
is approved for reduction of atherothrombotic events in patients with acute coronary syndrome (ACS). A randomized trials in patients with ACS have shown that clopidogrel plus aspirin produces significant relative risk (RR) reductions of cardiovascular (CV) events compared with aspirin
, this combination increases the risk of
upper gastrointestinal bleeding
. therefore, most guidelines recommend that patients prescribed dual therapy should also receive a proton pump inhibitor (PPI) to reduce the risk of gastrointestinal bleeding
PPI reach the parietal cell membrane as pro-drugs and cross it to accumulate in the canalicular space, where the environment is highly acid.
After a two-step pronation, the drug reacts with cysteine sulfhydryls on the gastric H+/K+-ATPase by forming covalent disulfide bonds thus inhibiting its activity.
Metaboliz action occurs by the intrahepatic P450 cytochrome system, especially CYP2C19 and CYP3A4, inhibiting them competitively.
CYP2C19 isoform is the
in the metabolism of many PPIs, which are also enzyme inhibitors of the CYP2C19 and CYP3A4 isoenzymes to varying degrees.
This has led to the assumption that some PPIs have the ability to inhibit metabolic activation of clopidogrel. The ability of a PPI to inhibit CYP2C19 activity could
reduce active form
of clopidogrel and cause a diminished response.
Thus, concomitant PPI therapy can further reduce clopidogrel metabolism, which predisposes patients to such
adverse CV events and death
Based on conclusion and US FDA and the European Medicines agency (EMEa) my recommendation is think about:
1) Indication of PPI needed?
2) Switch to safer drug?
3) Choice of PPI?
4) Dosing Time?
In the last years, pharmacological studies have reported an interaction between clopidogrel and PPIs. Subjects taking both drugs together showed a
in the clopidogrel-induced inhibition of platelet aggregation.