Drug General Information (ID: DDIRCYVSKF)
Drug Name			Alteplase		Drug Info		Warfarin		Drug Info
Drug Type		Protein/peptide				Small molecule
Therapeutic Class		Thrombolytics				Anticoagulants

Mechanism of Alteplase-Warfarin Interaction (Severity Level: Major)
Increased risk of bleeding Click to Show/Hide Mechanism Graph
Drug Name		Alteplase				Warfarin
Mechanism		Risk of bleeding Thrombolytic agent				Risk of bleeding Anticoagulant
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 Alteplase and Warfarin

Recommended Action
Management		Alteplase is contraindicated in patients with acute ischemic stroke who are currently taking oral anticoagulants and have an INR greater than 1.7. For other indications, risk versus benefit should be carefully weighed if patients who are currently taking oral anticoagulants (INR 2 to 3) are to receive thrombolytic therapy and patient selection should adhere to currently recommended criteria. Patients should be closely monitored for signs of bleeding, especially at arterial puncture sites. If oral anticoagulants are initiated following thrombolytic therapy, the dosage should be adjusted as appropriate to maintain therapeutic INR values. Patients should be closely monitored for clinical and laboratory signs of bleeding.

References
1	Arora RR, Magun AM, Grossman M, Katz J "Cholesterol embolization syndrome after intravenous tissue plasminogen activator for acute myocardial infarction." Am Heart J 126 (1993): 225-8. [PMID: 8322670]
2	Gupta BK, Spinowitz BS, Charytan C, Wahl SJ "Cholesterol crystal embolization-associated renal failure after therapy with recombinant tissue-type plasminogen activator." Am J Kidney Dis 21 (1993): 659-62. [PMID: 8503421]
3	Harder S, Klinkhardt U "Thrombolytics: drug interactions of clinical significance." Drug Saf 23 (2000): 391-9. [PMID: 11085346]
4	Hirsch J, Dalen J, Guyatt G, American College of Chest Physicians "The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Physicians." Chest 119(1 Suppl) (2001): 1S-2S. [PMID: 11157638]
5	Julian DG "A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial." BMJ 313 (1996): 1429-31. [PMID: 8973228]
6	Product Information. Abbokinase (urokinase). Abbott Pharmaceutical, Abbott Park, IL.
7	Product Information. Activase (alteplase). Genentech, South San Francisco, CA.
8	Product Information. Retavase (reteplase). Boehringer Mannheim, Gaithersburg, MD.
9	Product Information. Streptase (streptokinase). Astra USA, Westborough, MA.
10	Product Information. TNKase (tenecteplase) Genentech, South San Francisco, CA.