Possible Interaction Involving Phenytoin, Dexamethasone, and Antineoplastic Agents: A Case Report and Review

Abstract

To describe a patient with subtherapeutic phenytoin concentrations and to review the literature regarding a possible interaction between phenytoin and chemotherapeutic agents as well as dexamethasone. A 29-year-old white man with brain metastases secondary to malignant melanoma consistently had suboptimal phenytoin concentrations while receiving chemotherapy consisting of cisplatin, carmustine, dacarbazine, and tamoxifen. In addition, this patient received dexamethasone, which may have influenced his phenytoin concentrations. Case reports were identified through a MEDLINE search and by cross referencing the articles identified. The available literature addressing suboptimal phenytoin concentrations in the setting of chemotherapy is reviewed. Aggressive dosing of phenytoin may be required to achieve therapeutic concentrations in patients who are concurrently receiving chemotherapy and/or dexamethasone, especially in patients who fall outside the predictive pharmacokinetic model for phenytoin. Subtherapeutic phenytoin concentrations may be decreased secondary to several proposed mechanisms: (1) the patient falls outside the predicted pharmacokinetic population parameters for phenytoin, (2) phenytoin absorption is decreased secondary to chemotherapy-induced gastrointestinal toxicity, and (3) metabolism of phenytoin is increased secondary to chemotherapy agents.