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April 5, 2006

Interaction of Duloxetine and Warfarin Causing Severe Elevation of International Normalized Ratio

Author Affiliations

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

JAMA. 2006;295(13):1513-1518. doi:10.1001/jama.295.13.1517

To the Editor: We describe what we believe is the first report of a drug interaction between duloxetine hydrochloride and warfarin. The patient has provided consent for publication of this report, and it has received institutional review board approval.

Report of a Case

A 44-year-old woman, self-designated as white, homozygous for the factor V Leiden mutation, had been treated uneventfully for 1 year after an ischemic stroke with warfarin, 7.5 to 10 mg/d (mean international normalized ratio [INR], 2.2 [SD, 0.5]) (Figure). She had normal levels of protein C, protein S, homocysteine, and lipoprotein(a); homozygous wild-type genotypes for prothrombin (G20210A), MTHFR (C677T), PAI-1 (4G/5G), and platelet glycoprotein PL A1/A2; and no lupus anticoagulant or anticardiolipin antibodies. She had increased factor XI (179% [upper normal limit, 150%]) and plasminogen activator inhibitor activity (71.7 IU/mL [upper normal limit, 21.2]). She was being treated for poststroke seizures, migraine prophylaxis, panic disorder, and bronchospasm. She had no heart failure; thyroid, hepatic, or renal disease; or major weight loss or gain. She had a normal serum albumin–globulin ratio and reported taking no complementary or alternative medications.