Decreased phenytoin levels in patients receiving chemotherapy

Purpose and methods: Seizures and unexpectedly low phenytoin levels prompted a retrospective review of phenytoin doses and serum levels in patients with primary brain tumors following the administration of cisplatin and carmustine (BCNU) chemotherapy. Results: All patients who received three or more cycles of this chemotherapeutic regimen required an increase in their maintenance phenytoin dose to maintain therapeutic phenytoin levels. The average increase in the daily phenytoin dose was 41% (range, 20% to 100%). In addition, 17 of 26 (65%) assessable chemotherapy cycles were accompanied by a greater than 20% decrease in phenytoin levels or an increase in phenytoin requirements. Significant changes in phenytoin levels occurred as early as two days after administration of chemotherapy and were seen exclusively in treatment cycles that contained cisplatin. Five additional cases were found in the literature in which serum phenytoin concentrations decreased after the administration of antineoplastic agents. Conclusions: These observations are important to physicians treating patients who are receiving phenytoin. Serious consequences can be avoided by expecting changes in phenytoin dosage requirements after the administration of chemotherapy, monitoring serum levels frequently, and making appropriate adjustments in phenytoin dosages. Prospective evaluations are needed to confirm these observations, to define the chemotherapeutic agents that predispose patients to these alterations in phenytoin's pharmacology, and to determine if drugs other than phenytoin are affected by the administration of chemotherapy.