Drug Interaction Report

MONITOR: A possible interaction between phenytoin and intravenous immunoglobulin (IVIG) was suspected in a case of fatal hypersensitivity myocarditis. The mechanism of interaction has not been described. The case patient was a 43-year-old man with a past history of alcohol abuse who had been receiving phenytoin for the treatment of partial epilepsy for eight years. He was given intravenous immunoglobulin 0.4 g/kg for 5 days for suspected Guillain-Barre syndrome. On the second day after the last administration, the patient complained of abdominal pain, aching shoulders, and backache. He subsequently developed hypotension and died after attempts at resuscitation. An autopsy confirmed Guillain-Barre syndrome and revealed signs of a slight hepatitis with eosinophils as well as hypersensitivity (eosinophilic) myocarditis. There were no signs of alcoholic cardiomyopathy. Since phenytoin alone has been associated with hypersensitivity myocarditis, a contributory role for IVIG could not be established. Moreover, IVIG has been used successfully in some cases to treat anticonvulsant hypersensitivity syndrome, including that associated with phenytoin.

MANAGEMENT: Due to the serious nature of the possible interaction, clinicians should consider monitoring hematologic parameters such as eosinophil counts as well as blood pressure and ECG tracings if immunoglobulins are used in patients receiving phenytoin.