[A Case with the Increased PT-INR after the Addition of Mirtazapine to Warfarin Therapy].

OBJECTIVE

To report a case of warfarinization involving a patient who developed nasal bleeding and an elevated prothrombin time-international normalized ratio (PT-INR) after taking 15 mg of mirtazapine.

CASE SUMMARY

A 70-year-old Japanese man with anxiety and irritation was admitted to the ER of our hospital with nasal bleeding. His medical history included atrial fibrillation, treated with warfarin at 3.0 mg a day, hypertension, and diabetus mellitus. He had also been taking mirtazapine at 15 mg. He experienced nasal bleeding 4 days after the initiation of therapy with mirtazapine. His PT-INR markedly elevated from 1.21 before therapy to 7.93 after therapy. Both mirtazapine and warfarin were immediately discontinued by his cardiologist. One week later, PT-INR had normalized (1.00) and the nasal bleeding had resolved.

DISCUSSION

The metabolism of warfarin involves several cytochrome P450 isoenzymes, including CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Mirtazapine is metabolized primarily by CYP2D6 and CYP3A4, with lesser contributions by CYP1A2. A competitive enzyme inhibition may occur, with CYP3A4 metabolizing the two drugs. No drug interaction was seen with his other medications.

CONCLUSION

The coadministration of mirtazapine and warfarin can result in an increase in the anticoagulant effect of warfarin. This case shows the need to closely monitor potential drug interactions in the elderly, especially those taking mirtazapine and warfarin.