Interaction between warfarin and trazodone

BACKGROUND: It is well known that there are many drug interactions involving warfarin. However, few data have been supplied to guide clinicians concerning the interaction between trazodone and warfarin. CASE SUMMARY: Three clinically significant cases of suspected trazodone and warfarin interactions were identified in a retrospective chart review based on changes in the prothrombin time (PT) and international normalized ratio (INR) that were not explained by other factors. In each of the cases, the INR changed by > or = 1.0 after the initiation or discontinuation of trazodone. In the patients who started trazodone, a subsequent decrease in the PT and INR resulted; conversely, the PT and INR increased in the patient who stopped trazodone therapy. Although none of the patients experienced adverse effects due to the marked changes in PT and INR, the warfarin dosages had to be adjusted accordingly on initiation and discontinuation of trazodone. DISCUSSION: These cases show that there is a potentially clinically significant interaction between trazodone and warfarin. The time to onset of the interaction is variable; the mechanism behind it is not known, but it may involve substrate or protein-binding competition. CONCLUSIONS: The use of trazodone on an as-needed basis for sleep is strongly discouraged in patients who are receiving warfarin, due to the difficulty of achieving a therapeutic PT and INR. Until more is known, patients and clinicians should be educated about this potential interaction and monitor for changes in the anticoagulant effects when trazodone is initiated or stopped.

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