[CK] P2Y12 Study - [Q] Clopidogrel - polymorphism(CYP) <- NOT WITH OMEPRAZOLE(Decrease its absorption)

Clopidogrel activation is prevented by CYP2C19 inhibitors such as fluvoxamine, fluoxetine, omeprazole, and carbamazepine. CYP2C19 polymorphisms influence clopidogrel activation; poor metabolizers (CYP2C19*2/*2, *2/*3, or *3/*3) accrue less benefit from clopidogrel therapy.

he antiplatelet drug clopidogrel (Plavix, and others) reduces major cardiovascular events, but can cause bleeding. Proton pump inhibitors (PPIs) are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect. FDA-approved labeling recommends avoiding concurrent use of the PPIs omeprazole and esomeprazole with clopidogrel.

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Prasugrel’s drug-drug interactions are limited to weak CYP2B6 inhibition; it has clinically significant interactions with narrow therapeutic window CYP2B6 substrates (eg, cyclophosphamide and efavirenz) only.

Ticagrelor is a CYP3A4 and P-glycoprotein substrate and is liable to cumulative bradycardia with other bradycardic medications (eg, beta-blockers and calcium channel blockers). CYP3A4 and P-glycoprotein inhibitors increase ticagrelor levels, inducers do the opposite, and ticagrelor can increase the concentrations of other CYP3A4 substrates. Ticagrelor can both increase digoxin’s concentration and potentiate digoxin toxicity.

Pharmacists are poised to select the best P2Y₁₂ inhibitor based on stenting history, diabetes diagnosis, gastrointestinal or cerebral bleed history, and pharmacokinetics.

Pharmacists can also stress the importance of adherence, bleeding risk, and agent affordability during discharge counseling following a stenting procedure.

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Concerns about PPI use and clopidogrel are now out of date, Dr. Brener asserted, due to the availability of alternative antiplatelet therapies and mounting evidence that the association is not real. Clinicians should instead focus on weighing whether patients need to be on PPIs in the first place, he added.

No problem with 

other PPI  - Plavix (possibility but not)

PPI - ticagrelor = no problem at all!