Clinical implications of drug-drug interactions with P2Y12 receptor inhibitors

Polypharmacy in patients undergoing coronary artery stenting or in those presenting with an acute coronary syndrome is common. Nevertheless, the risk of drug-drug interactions in patients treated simultaneously with P2Y12 receptor inhibitors is less well considered in routine clinical practice. Whereas the irreversible P2Y12 receptor inhibitors clopidogrel and prasugrel are prodrugs requiring cytochrome P450 (CYP) enzymes for metabolic activation, such activation is not necessary for the direct-acting reversible P2Y12 receptor inhibitor ticagrelor. Several drugs frequently used in cardiology have been shown to interact with the metabolism of P2Y12 receptor inhibitors in pharmacodynamic studies. Whereas several drug-drug interactions have been described for clopidogrel and ticagrelor, prasugrel seems to have a low potential for drug-drug interactions. The clinical implications of these interactions have raised concern. In general, concomitant administration of P2Y12 receptor antagonists and strong inhibitors or inducers of CYP3A/CYP2C19 should be performed with caution in patients treated with clopidogrel/ticagrelor. Under most circumstances, clinicians have the option of prescribing alternative drugs with less risk of drug-drug interactions when used concomitantly with P2Y12 receptor inhibitors.