Warfarin-fluoxetine and Diazepam-fluoxetine Interaction

Fluoxetine and its metabolite norfluoxetine are eliminated by oxidative metabolism via the CYP450 system and may inhibit the oxidative metabolism of other drugs to various degrees. A fluoxetine-warfarin interaction has been postulated, but is not well documented in the literature. The elimination of diazepam may also be inhibited by fluoxetine. An elderly man was prescribed these three drugs in combination and experienced such an interaction. He developed an elevated international normalized ratio (INR) and died from a cerebral hemorrhage. He also manifested drug delirium secondary to inhibited diazepam metabolism. In elderly patients receiving fluoxetine, lorazepam or oxazepam would be safer alternatives to diazepam since they are conjugated in the liver. Patients stabilized on warfarin should be monitored closely for changes in INR if fluoxetine is added or deleted.