Improved ticagrelor antiplatelet effect on discontinuation of phenytoin.
OBJECTIVE
To report the influence of phenytoin on the antiplatelet effects of ticagrelor using a validated platelet aggregation study.


METHODS
A 71-year-old man with coronary artery disease underwent percutaneous coronary intervention to revascularize several major coronary arteries. The patient was previously on phenytoin and was initiated on ticagrelor for antiplatelet therapy following stent placement. While the patient was receiving both drugs, platelet aggregation studies revealed less platelet inhibition than would be expected in a patient not taking a concomitant inducer of ticagrelor metabolism. On discontinuation of phenytoin, platelet inhibition improved.


CONCLUSIONS
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist following placement of coronary stents is critical to prevent stent thrombosis and subsequent myocardial infarction. Ticagrelor is a recently approved P2Y12 receptor antagonist that is subject to drug-drug interactions involving the hepatic cytochrome P450-3A4 enzyme system because of its metabolic elimination pathway. This case demonstrates ticagrelor's drug-drug interaction with phenytoin through a platelet aggregation study and supports the manufacturer recommendation to avoid the combination of ticagrelor with any known inducers of cytochrome P450-3A4 metabolism.


CONCLUSIONS
The combination of ticagrelor and phenytoin may represent a potentially clinically significant drug-drug interaction because of phenytoin induction of ticagrelor metabolism and reduced P2Y12 receptor inhibition in patients who have recently undergone percutaneous coronary intervention and cardiac stent placement.
Memorial Hermann-Texas Medical Center, Houston, TX, USA.
Phillip
P
Weeks
Adam
A
Sieg
Khashayar
K
Vahdat
Farshad
F
Raissi
Sriram
S
Nathan
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D010672:Phenytoin / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D000077486:Ticagrelor
D010975:Platelet Aggregation Inhibitors; D010672:Phenytoin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077486:Ticagrelor; D000241:Adenosine
drug interaction; platelet function studies; ticagrelor