Inclusion criteria (Powers, et al., 2018)

• Diagnosis of ischemic stroke causing measurable neurological deficit
• 18 years of age or older
• Onset of symptoms < 3 hours
  • Includes patients with severe stroke and patients with mild but disabling stroke symptoms
  • Equally effective in patients < 80 and > 80 years of age
• For select patients with symptom onset 3- to 4.5- hours:
  • 80 years of age or less
  • No history of diabetes mellitus and prior stroke, no current oral anticoagulant use, NIHSS score ≤ 25, no anticoagulants, cerebral imaging showing ischemia involving less than one third of middle cerebral artery (MCA) territory
• Blood pressure (BP) that can be lowered safely (< 185/110 mm Hg) with antihypertensive agents.
• Initial glucose > 50 mg/dL
• Non-contrast computed tomography (NCCT) showing early mild-moderate ischemic changes.
• Patients taking mono-antiplatelet therapy or combination therapy (i.e. aspirin and clopidogrel) and patients with end-stage renal disease on hemodialysis and normal aPTT are eligible for therapy.

Contraindications (Powers, et al., 2018)

• Unclear time and/or unwitnessed symptom onset and last known baseline state > 3 or 4.5 hours
• Current or history of intracranial hemorrhage
• CT scan showing hypoattenuation or hypoperfusion representing irreversible injury
• Recent (within 3 months) ischemic stroke, severe head trauma, or intracranial/intraspinal surgery
• Subarachnoid hemorrhage
• Gastrointestinal (GI) malignancy or GI bleed within 21 days of stroke event
• Intracranial conditions that may increase the risk of bleeding such as intracranial neoplasm, arteriovenous malformation, or aneurysm
• Coagulopathy: Platelet count < 100,000/mm³, INR > 1.7, aPTT > 40 seconds, or PT > 15 seconds
• Low molecular weight heparin (LMWH) treatment doses within the previous 24 hours
• Current use of anticoagulant with INR > 1.7 or PT > 15 seconds
• Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated laboratory tests
• Concurrent use of glycoprotein IIb/IIIa receptor inhibitors
• Infective endocarditis
• Aortic arch dissection
• Intra-axial intracranial neoplasm – lesions located within the brain tissue

Note: See current clinical practice guidelines for complete list of recommendations for treatment with parenteral alteplase and relative indications.

Pregnancy Risk Category: C

Dosage and Administration

Available forms: 50-mg vial, 100-mg vial

Dosage: Dose is calculated based on patient weight (0.9 mg/kg) with a maximum total of 90 mg over 60 minutes. Ten percent of total dose given as an IV bolus over 1 minute, followed by an IV infusion of the remainder of the dose over 1 hour.

Administration:

• May be administered IV or intra-arterially (intra-arterial administration is an off-label route).
• May be given to eligible patients even if endovascular therapies (EVTs) are being considered.
• Consult package insert for complete instructions on medication preparation, reconstitution and administration.

Nursing Considerations

• BEFORE administration:
  • Carefully lower blood pressure (BP) to maintain systolic BP < 185 mmHg and diastolic BP < 110 mmHg before initiating fibrinolytic therapy (Powers, et al., 2018).
  • Due to an increased risk of intracranial bleeding, check INR, PTT and blood glucose prior to administration.
  • Assess for exclusion criteria/contraindications.
  • Explain use and administration of the drug to the patient and the family; tell them to report adverse reactions immediately.
  • Admit to the intensive care unit (ICU) for monitoring.
• DURING administration:
  • Maintain strict bedrest during treatment.
  • Measure BP and perform neurological assessment every 15 minutes during infusion for 2 hours, then every 30 minutes for 6 hours, then hourly until 24 hours after treatment.
    • Increase frequency of BP measurements if SBP > 180 mm Hg or if DPB > 105 mm Hg; administer antihypertensive as needed to maintain these levels.
  • If any change in neurological status or symptoms occurs, such as severe headache, acute hypertension, nausea or vomiting, or worsening neurological examination, the alteplase administration should be stopped and a CT scan obtained.
  • Avoid invasive procedures and I.M. injections, and perform venipunctures carefully and only as required, avoiding internal jugular and subclavian venous punctures.
  • Closely monitor the patient for internal bleeding and frequently assess all puncture sites.
    • If serious bleeding occurs, stop the alteplase infusion immediately.
• AFTER administration:
  • Monitor BP and neurologic status every 5 minutes for the first 15 minutes after administration, then every 15 minutes for 2 hours, every 30 minutes for 6 hours, and hourly for 16 hours after treatment. After the initial 24 hours, monitor vital signs, control blood pressure, and perform neurological assessments frequently per your facility’s policy.
  • Maintain BP < 180/105 mmHg for at least 24 hours after treatment.
  • Hold antiplatelet or anticoagulation therapy and invasive procedures for 24 hours following administration.
  • Monitor for serious adverse events, such as bleeding and angioedema.
    • Concomitant use of angiotensin-converting enzyme (ACE) inhibitors may increase the risk of orolingual angioedema.
    • Concomitant use of anticoagulants and drugs that inhibit platelet function increase the risk of bleeding.
  • Delay insertion of nasogastric tubes, indwelling bladder catheters, or intra-arterial pressure catheters if patient can be managed without them.
  • Obtain follow-up CT or MRI scan 24 hours after treatment before starting anticoagulants or antiplatelet agents.

Adverse reactions

• Bleeding (most common)
• Orolingual angioedema
• Arrhythmias
• Hypotension
• Edema 
• Cholesterol embolization
• Venous thrombosis
• Re-embolization of deep venous thrombi (DVT) in patients with pulmonary embolism
• Nausea
• Vomiting
• Hypersensitivity reactions

Management of Symptomatic Bleeding Within 24 Hours After Administration of IV Alteplase (Powers, et al., 2018)

• Stop alteplase infusion.
• Obtain CBC, PT (INR), aPTT, fibrinogen level, and type and cross-match.
• Obtain emergent nonenhanced head CT.
• Per order, administer cryoprecipitate (includes factor VIII): 10 U infused over 10-30 minutes (onset in 1 hour, peaks in 12 hour); administer additional dose for fibrinogen level < 200 mg/dL. 
• Per order, administer tranexamic acid 1000 mg IV infused over 10 min OR Ɛ-aminocaproic acid 4-5 g over 1 hour, followed by 1 g IV until bleeding is controlled.
• Obtain hematology and neurosurgery consult.
• Manage BP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), temperature, and glucose.

Management of Orolingual Angioedema Associated with IV Alteplase (Powers, et al., 2018)

• Maintain airway.
  • Intubation may not be needed if edema is limited to anterior tongue and lips.
  • Edema involving larynx, palate, floor of mouth, oropharynx with rapid progression (within 30 minutes) poses higher risk of respiratory compromise requiring intubation.
  • Awake fiberoptic intubation is preferred.
• As ordered, perform the following:
  • Discontinue IV alteplase infusion and hold ACE-inhibitors.
  • Administer IV methylprednisolone 125 mg.
  • Administer IV diphenhydramine 50 mg.
  • Administer ranitidine 50 mg IV or famotidine 20 mg IV.
  • If there is an increase in angioedema, administer epinephrine (0.1%) 0.3 mL subcutaneously or by nebulizer 0.5 mL.
  • Administer icatibant (selective bradykinin B2 receptor antagonist), 3 mL (30 mg) subcutaneously in abdomen.