Abstracts

Antiepileptic drug (AED) related adverse drug reactions (ADRs) are a relatively common problem that complicates management of patients. Studies have reported 10% or more of patients on AEDs develop abnormalities involving skin, liver and bone marrow. Observation based approaches for identifying patients at increased risk for ADRs are currently lacking. We encountered a group of patients with a history of malignancy who received AEDs for treatment of epilepsy or other disorders (e.g., neuropathy) and developed an AED related ADR. We report an apparent relationship between disease state (cancer) and development of an AED related ADR.
Patients were identified through direct patient interaction by the Pharmacy service and through review of the Pharmacy computerized database of ADRs. Key characteristics that were used included a recent or past history of malignancy, exposure to an AED (for seizures or other disorders). Clinical records were searched to provide supplemental information regarding history not available in the Pharmacy database.
We identified a series of 7 patients who developed one or more AED related-ADRs. Demographic features include: Gender: 6 male and 1 female. Age: Range (37-73 year) Mean (56). 6/7 (86%) of patients received phenytoin; 1/7 (14%) received carbamazepine and lamotrigine. The most common ADR was skin rash seen in 6/7 patients (86%) ; 1/7 patients (14%) developed a fever attributed to phenytoin. Tumor types detected included the following: lung cancer (small cell and non-small cell [ndash]1 patient each); astrocytoma (2 patients); meningioma (2 patients); malignant melanoma (1 patient). 2/7 patients (28%) received cranial irradiation therapy either in the distant past or immediately prior to development of the ADR..
A putative connection linking cranial irradiation as a potentially significant risk per se for cancer patients receiving AED therapy (especially phenytoin) has been suggested in several publications. In our patient sample however, only 1/7 patients (14%) had a temporal connection between radiation therapy and the subsequent development an ADR. This suggests that for the remaining 6/7 patients (86%) an alternative explanation must be found for the development of the AED-related ADR. Our preliminary data suggests an underlying malignancy may be an independent risk factor for developing AED related ADRs. Additional studies are underway to verify this.