Activase (Alteplase) - Drug Interactions, Contraindications, Overdosage

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