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Drug Interactions between Kinlytic and tirofiban

This report displays the potential drug interactions for the following 2 drugs:

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Major

urokinase tirofiban

Applies to: Kinlytic (urokinase) and tirofiban

MONITOR CLOSELY: The intended and unintended effects of glycoprotein IIb/IIIa inhibitors and thrombolytic agents are additive, such that there is an increased frequency of major bleeding complications, including intracranial hemorrhage, retroperitoneal bleeding, spontaneous gastrointestinal (GI) and genitourinary (GU) bleeding among patients receiving both agents compared with the risk associated with the use of either agent alone. In one clinical trial, the risk of bleeding increased by twofold when abciximab was given after full-dose thrombolytics, while other studies have not reported an increased risk. Fatalities have occurred. Arterial puncture sites may be most problematic.

MANAGEMENT: It is recommended that these drugs be used together only when indicated by skilled personnel who are qualified and equipped to detect and treat bleeding complications. The successful use of combination therapy with glycoprotein IIb/IIIa inhibitors and reduced doses of thrombolytics has been reported in clinical trials. Patients should be closely monitored for signs of bleeding, especially at arterial puncture sites. Thrombolytic and/or glycoprotein inhibitor therapy should be discontinued immediately if serious or uncontrollable bleeding occurs.

References

  1. "Product Information. ReoPro (abciximab)." Lilly, Eli and Company PROD (2001):
  2. "Product Information. Retavase (reteplase)." Boehringer Mannheim PROD (2001):
  3. "Product Information. Aggrastat (tirofiban)." Merck & Co., Inc PROD (2001):
  4. "Product Information. Integrilin (eptifibatide)." Schering Corporation PROD (2001):
  5. Sundlof DW, Rerkpattanapitat P, Wongpraparut N, Pathi P, Kotler MN, Jacobs LE, Ledley GS, Yazdanfar S "Incidence of bleeding complications associated with Abciximab use in conjunction with thrombolytic therapy in patients requiring percutaneous transluminal coronary angioplasty." Am J Cardiol 83 (1999): 1569-71
  6. Califf RM "Glycoprotein IIb IIIa blockade and thrombolytics: Early lessons from the SPEED and GUSTO IV trials." Am Heart J 138 (1999): s12-5
  7. Miller JM, Smalling R, Ohman EM, Bode C, Betriu A, Kleiman NS, Schildcrout JS, Bastos E, Topol EJ, Califf RM "Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (Reteplase or alteplase) during acute myocardial infarction (Results from the GUSTO-III trial)." Am J Cardiol 84 (1999): 779-84
  8. deLemos JA, Antman EM, Gibson CM, McCabe CH, Giugliano RP, Murphy SA, Coulter SA, Anderson K, Scherer J, Frey MJ, VanderWi "Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction - Observations from the TIMI 14 trial." Circulation 101 (2000): 239-43
  9. "Product Information. TNKase (tenecteplase)." Genentech PROD (2001):
  10. Jong P, Cohen EA, Batchelor W, Lazzam C, Kreatsoulas C, Natarajan MK, Strauss BH "Bleeding risks with abciximab after full-dose thrombolysis in rescue or urgent angioplasty for acute myocardial infarction." Am Heart J 141 (2001): 218-25
  11. Cantor WJ, Kaplan AL, Velianou JL, Sketch MH, Barsness GW, Berger PB, Ohman EM "Effectiveness and safety of Abciximab after failed thrombolytic therapy." Am J Cardiol 87 (2001): 439+
  12. deLemos JA, Gibson CM, Antman EM, Murphy SA, Morrow DA, Schuhwerk KC, Schweiger M, Coussement P, VandeWerf F, Braunwald E "Abciximab and early adjunctive percutaneous coronary intervention are associated improved ST-segment resolution after thrombolysis: Observations from the TIMI 14 trial." Am Heart J 141 (2001): 592-8
  13. Gibson CM, deLemos JA, Murphy SA, Marble SJ, McCabe CH, Cannon CP, Antman EM, Braunwald E "Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction - A TIMI 14 substudy." Circulation 103 (2001): 2550-4
  14. Schweiger MJ, Cannon CP, Murphy SA, et al. "Early coronary intervention following pharmacologic therapy for acute myocardial infarction (the combined TIMI 10B-TIMI 14 experience)." Am J Cardiol 88 (2001): 831-6
  15. Mak KH, Lee LH, Wong A, et al. "Thrombin generation and fibrinolytic activities among patients receiving reduced-dose alteplase plus abciximab or undergoing direct angioplasty plus abciximab for acute myocardial infarction." Am J Cardiol 89 (2002): 930-936
  16. Lincoff AM, Califf RM, Van De Werf F, et al. "Mortality at 1 Year With Combination Platelet Glycoprotein IIb/IIIa Inhibition and Reduced-Dose Fibrinolytic Therapy vs Conventional Fibrinolytic Therapy for Acute Myocardial Infarction: GUSTO V Randomized Trial." JAMA 288 (2002): 2130-5
  17. Dubois CL, Belmans A, Granger CB, et al. "Outcome of urgent and elective percutaneous coronary interventions after pharmacologic reperfusion with tenecteplase combined with unfractionated heparin, enoxaparin, or abciximab." J Am Coll Cardiol 42 (2003): 1178-85
  18. Gurm HS, Lincoff AM, Lee D, et al. "Outcome of acute ST-segment elevation myocardial infarction in diabetics treated with fibrinolytic or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition; Lessons from the GUSTO V trial." J Am Coll Cardiol 43 (2004): 542-8
  19. Kastrati A, Mehilli J, Schlotterbeck K, et al. "Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial." JAMA 291 (2004): 947-54
  20. 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
  21. Bush HS "Combination pharmacotherapy with reduced-dose fibrinolytic and platelet GP IIb/IIIa inhibition." J Emerg Med 25 (2004): 421-6
  22. Morris DC, Silver B, Mitsias P, et al. "Treatment of acute stroke with recombinant tissue plasminogen activator and abciximab." Acad Emerg Med 10 (2003): 1396-9
  23. Savonitto S, Armstrong PW, Lincoff AM, et al. "Risk of intracranial haemorrhage with combined fibrinolytic and glycoprotein IIb/IIIa inhibitor therapy in acute nyocardial infarction: dichotomours response as a function of age in the GUSTO V trial." Eur Heart J 24 (2003): 1807-14
  24. Drescher P, McGuckin J, Rilling WS, Crain MR "Catheter-directed thrombolytic therapy in peripheral artery oclusions: combining reteplase and abciximab." AJR Am J Roentgenol 180 (2003): 1385-91
  25. Topol EJ, GUSTO V Investigators "Reprerfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial." Lancet 357 (2001): 1905-14
  26. Antman EM, Gibson CM, de Lemos JA, et al. "Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14." Eur Heart J 21 (2000): 1944-53
  27. Califf RM "Combination therapy for acute myocardial infarction: fibrinolytic therapy and glycoprotein IIb/IIIa inhibition." Am Heart J 139 (2000): S33-7
View all 27 references

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Therapeutic duplication warnings

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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.
Unknown No interaction information available.

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