Ticlopidine impairs phenytoin clearance

Ticlopidine is an antiplatelet agent used in the prophylaxis of peripheral and cerebrovascular diseases, [1-3] ischemic heart disease, [1,3] and vascular complications of diabetes mellitus. [4] In healthy volunteers ticlopidine reduces the clearance of theophylline [5] and antipyrine, [6] probably by inhibiting the activity of cytochrome P450 enzymes. On the basis of these observations, the package insert in some countries contains a warning advising caution when ticlopidine is introduced in patients receiving therapy with highly metabolized drugs. We report a case of metabolic phenytoin-ticlopidine interaction in which phenytoin plasma concentrations increased and CNS toxicity appeared when ticlopidine was added to the therapeutic regimen. A 65-year-old man had a history of complex partial seizures, sometimes with secondary generalization, which started at the age of 52 years. A brain CT scan obtained at this time was normal. He had been treated with different antiepileptic regimens for about 10 …