Drug General Information (ID: DDIBYJHPW9)
Drug Name			Warfarin		Drug Info		Clopidogrel		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Anticoagulants				Antiplatelet Agents
Structure

Mechanism of Warfarin-Clopidogrel Interaction (Severity Level: Major)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Warfarin				Clopidogrel
Mechanism		Risk of bleeding Anticoagulant				Risk of bleeding Antiplatelet
Key Mechanism Factor 1
		Factor Name		Bleeding
		Factor Description		Patients may be at risk for bleeding when the outcome of a disease or disease treatment confounds the standard mechanisms for maintaining hemostasis. Signs or symptoms of abnormal bleeding include: bleeding that takes a long time to stop (including nosebleeds, bleeding gums, bleeding from cuts and abrasions, and menstrual bleeding); severe unexplained bruising, or bruising that becomes larger; blood in the urine or stool, etc.
Mechanism Description		Increased risk of bleeding by the combination of Warfarin and Clopidogrel

Recommended Action
Management		Caution and close monitoring of the INR and other bleeding parameters are recommended if clopidogrel is used in combination with an oral anticoagulant. Patients should be advised to promptly report any signs of bleeding to their physician, 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.

References
1	Anand S, Yusuf S, Xie C, et al. "Oral anticoagulant and antiplatelet therapy and peripheral arterial disease." N Engl J Med 357 (2007): 217-27. [PMID: 17634457]
2	Buresly K, Eisenberg MJ, Zhang X, Pilote L "Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction." Arch Intern Med 165 (2005): 784-9. [PMID: 15824298]
3	Delaney JA, Opatrny L, Brophy JM, Suissa S "Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding." CMAJ 177 (2007): 347-51. [PMID: 17698822]
4	Eikelboom JW, Hirsh J "Combined antiplatelet and anticoagulant therapy: clinical benefits and risks." J Thromb Haemost 5 (2007): 255-63. [PMID: 17635734]
5	Hermosillo AJ, Spinler SA "Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too danterous?" Ann Pharmacother 42 (2008): 790-805. [PMID: 18477734]
6	Johnson SG, Rogers K, Delate T, Witt DM "Outcomes associated with combined antiplatelet and anticoagulant therapy." Chest 133 (2008): 948-54. [PMID: 18198244]
7	Lidell C, Svedberg LE, Lindell P, Bandh S, Job B, Wallentin L "Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation." Thromb Haemost 89 (2003): 842-6. [PMID: 12719782]
8	Product Information. Plavix (clopidogrel). Bristol-Myers Squibb, Princeton, NJ.
9	Tay KH, Lane DA, Lip GY "Bleeding risks with combination of oral anticoagulation plus antiplatelet therapy: is clopidogrel any safer than aspirin when combined with warfarin?" Thromb Haemost 100 (2008): 955-7. [PMID: 19132214]