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Drug interactions between Cymbalta and warfarin

Results for the following 2 drugs:
Cymbalta (duloxetine)

Interactions between your selected drugs

warfarin ↔ duloxetine

Applies to:warfarin and Cymbalta (duloxetine)

MONITOR: Limited data suggest that duloxetine may potentiate the hypoprothrombinemic effects of warfarin. The mechanism of interaction is unknown. In one case report, a 44-year-old woman who had been treated uneventfully with warfarin (7.5 to 10 mg/day) for one year demonstrated a significantly increased INR after initiation of duloxetine (30 mg/day) for depression. Her other medications included atorvastatin (10 mg/day), lamotrigine (50 mg/day), topiramate (200 mg/day), clonazepam (2 mg/day), and albuterol (extended-release tablets 4 mg twice a day), all of which she had been taking without incident. Fifty-five days after starting duloxetine, the patient developed petechiae and purpura in association with an INR of 5.0. Warfarin, but not duloxetine, was stopped on day 58. Her INR continued to increase and was greater than 19 on day 85, with a plasma warfarin level of 5.3 mcg/mL. She was given intravenous vitamin K, whereupon her INR decreased briefly but increased again to 6.4 on day 94. At that point, her levels of vitamin K-dependent clotting factors were critically low. Duloxetine was stopped, and INR decreased to 1.2 by day 98. Warfarin was restarted on day 110. By day 140, her INR was stable at 2.2 while maintained on her original dosage of warfarin. The time course described in the case report supports an interaction between duloxetine and warfarin. Other potential causes such as thyroid disease, hepatic or renal impairment, platelet dysfunction, alternative self-medication, and warfarin self-intoxication were excluded.

MANAGEMENT: Until more data are available, caution may be advisable if duloxetine is used in combination with warfarin. The INR should be checked frequently and warfarin dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of duloxetine in patients who are stabilized on their warfarin regimen. The same precaution may be applicable during therapy with other oral anticoagulants, although clinical data are lacking. Patients should be advised to promptly report any signs of bleeding to their doctor, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.


  1. Glueck CJ, Khalil Q, Winiarska M, Wang P "Interaction of duloxetine and warfarin causing severe elevation of international normalized ratio." JAMA 295 (2006): 1517-8

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Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to determine using this tool alone given the large number of variables that may apply.

Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.

Do not stop taking any medications without consulting your healthcare provider.

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