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Activase (Alteplase) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

The interaction of Activase with other cardioactive or cerebroactive drugs has not been studied. In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and Abciximab) may increase the risk of bleeding if administered prior to, during, or after Activase therapy.

There have been post-marketing reports of orolingual angioedema associated with the use of Activase. Many patients, primarily acute ischemic stroke patients, were receiving concomitant Angiotensin-converting enzyme inhibitors. (See PRECAUTIONS: General and ADVERSE REACTIONS: Allergic Reactions).

CONTRAINDICATIONS

ACUTE MYOCARDIAL INFARCTION OR PULMONARY EMBOLISM

Activase therapy in patients with acute myocardial infarction or pulmonary embolism is contraindicated in the following situations because of an increased risk of bleeding:

  • Active internal bleeding
  • History of cerebrovascular accident
  • Recent intracranial or intraspinal surgery or trauma (see WARNINGS)
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Known bleeding diathesis
  • Severe uncontrolled hypertension

ACUTE ISCHEMIC STROKE

Activase therapy in patients with acute ischemic stroke is contraindicated in the following situations because of an increased risk of bleeding, which could result in significant disability or death:

  • Evidence of intracranial hemorrhage on pretreatment evaluation
  • Suspicion of subarachnoid hemorrhage on pretreatment evaluation
  • Recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, or previous stroke
  • History of intracranial hemorrhage
  • Uncontrolled hypertension at time of treatment (e.g., > 185 mm Hg systolic or > 110 mm Hg diastolic)
  • Seizure at the onset of stroke
  • Active internal bleeding
  • Intracranial neoplasm, arteriovenous malformation, or aneurysm
  • Known bleeding diathesis including but not limited to:
    • Current use of oral anticoagulants (e.g., warfarin sodium) or an International Normalized Ratio (INR) >1.7 or a prothrombin time (PT) > 15 seconds
    • Administration of heparin within 48 hours preceding the onset of stroke and have an elevated activated partial thromboplastin time (aPTT) at presentation
    • Platelet count < 100,000/mm3

REFERENCES

  1. Mueller H, Rao AK, Forman SA, et al. Thrombolysis in myocardial infarction (TIMI): comparative studies of coronary reperfusion and systemic fibrinogenolysis with two forms of recombinant tissue-type plasminogen activator. J Am Coll Cardiol. 1987;10:479-90.
  2. Topol EJ, Morriss DC, Smalling RW, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (Activase®) in acute myocardial infarction. J Am Coll Cardiol. 1987;9:1205-13.
  3. Seifried E, Tanswell P, Ellbrück D, et al. Pharmacokinetics and haemostatic status during consecutive infusions of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction. Thromb Haemostas. 1989;61:497-501.
  4. Tanswell P, Tebbe U, Neuhaus K-L, et al. Pharmacokinetics and fibrin specificity of Alteplase during accelerated infusions in acute myocardial infarction. J Am Coll Cardiol. 1992;19:1071-5.
  5. De Wood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. New Engl J Med. 1980;303:897-902.
  6. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in myocardial infarction (TIMI) trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation. 1987;76(1):142-54.
  7. Guerci AD, Gerstenblith G, Brinker JA, et al. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. New Engl J Med. 1987;317:1613-18.
  8. O'Rourke M, Baron D, Keogh A, et al. Limitation of myocardial infarction by early infusion of recombinant tissue-plasminogen activator. Circulation. 1988;77:1311-15.
  9. Wilcox RG, von der Lippe G, Olsson CG, et al. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction: ASSET. Lancet. 1988;2:525-30.
  10. Hampton JR, The University of Nottingham. Personal communication.
  11. Van de Werf F, Arnold AER, et al. Effect of intravenous tissue-plasminogen activator on infarct size, left ventricular function and survival in patients with acute myocardial infarction. Br Med J. 1988;297:1374-9.
  12. The National Institute of Neurological Disorders and Stroke t-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. New Engl J Med. 1995;333:1581-7.
  13. Goldhaber SZ, Kessler CM, Heit J, et al. A randomized controlled trial of recombinant tissue plasminogen activator versus urokinase in the treatment of acute pulmonary embolism. Lancet. 1988;2:293-8.
  14. Aylward P, Wilcox R, Horgan J, White H, Granger C, Califf R, et al. for the GUSTO-I Investigators. Relation of increased arterial blood pressure to mortality and stroke in the context of contemporary thrombolytic therapy for acute myocardial infarction: a randomized trial. Ann Int Med. 1996;125:891-900.
  15. Califf RM, Topol EJ, George BS, et al. Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction. Am J Med. 1988;85:353-9.
  16. Bovill EG, Terrin ML, Stump DC, et al. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction: results from the thrombolysis in myocardial infarction (TIMI), Phase II trial. Ann Int Med. 1991;115(4):256-65.
  17. National Heart Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial infarction salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet. 1988;1:203-7.
  18. Gore JM, Sloan M, Price TR, et al. and the TIMI Investigators. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation. 1991;83:448-59.
  19. Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. for the ECASS Study Group. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017-25.

Activase®, (Alteplase)                                                              4800511

Manufactured by                                          Revision Date October 2002

GENENTECH, INC.                            FDA Approval Date May 2002

1 DNA Way                                                      © 2002 Genentech, Inc.

South San Francisco, CA 94080-4990

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