We observed a drug interaction between the antihistamine terfenadine (Seldane, Marion Merrell Dow, Kansas City, Missouri) and the anticonvulsant carbamazepine (Tegretol, Basel Pharmaceuticals, Summit, New Jersey) that warrants the attention of practitioners.

An 18-year-old woman (weight, 39.3 kg) who had had hip disarticulation for osteosarcoma and who was on anticonvulsant therapy after treatment of brain metastases came to the hospital with symptoms of confusion, disorientation, visual hallucinations, nausea, and ataxia. Her history was unremarkable for recent infections, ingestion, or trauma. She had a history of atopy, and her symptoms began shortly after taking terfenadine, 60 mg twice daily by mouth, for symptomatic relief of rhinitis. A serum level of carbamazepine was 8.9 mg/L (normal, 4 to 12 mg/L). Because terfenadine and carbamazepine are highly protein bound, we speculated that the terfenadine had displaced the carbamazepine, resulting in a higher than normal free carbamazepine level, which we tested for at an outside laboratory. We withheld further terfenadine and the symptoms cleared. The free carbamazepine level results were returned later in the week at 6.0 mg/L, almost three times the upper limit of normal (normal, 1.6 to 2.2 mg/L). After discontinuing terfenadine, her free carbamazepine level returned to within the normal range (2.1 mg/L), whereas the total level remained at 8.9 mg/L.

We could find no other report of this potentially dangerous complication of concomitant therapy with terfenadine and carbamazepine.