TNKase or Activase

• In any emergency department, an acute stroke is an urgent medical event with complex institution-specific treatment protocols for eligible patients. Medications, such as thrombolytics, carry an increased risk of significant patient harm when used in error. 
• Intravenous alteplase (IV) is the only approved treatment for acute ischemic stroke, but tenecteplase (TNK), an engineered plasminogen activator, is an alternative thrombolytic agent gaining favor 
• Decisions for thrombolytic therapy are based on the risks and benefits of each individual patient. Consult your institution’s specific policies and procedures on thrombolytic therapy and be cognizant of potential changes in drug therapy for acute stroke.  

A Case Study

A 56-year-old man with a history of atrial fibrillation on Coumadin arrives in your emergency department (ED) 90 minutes after the sudden onset of aphasia, left-sided weakness, gait imbalance and a decreased level of consciousness. The STAT non-contrast head CT is consistent with an acute left middle cerebral artery ischemic stroke. There was no hemorrhage.  

With no contraindications, the patient is a candidate for tissue plasminogen activatoral (tPA) administration (thrombolytic therapy). Fifteen minutes after arrival, a complete blood count (CBC) and coagulation studies were still pending. To speed up treatment, the ED physician wrote for intravenous (IV) tPA.

Unlike high-volume emergency departments that have dedicated stroke teams and use bundled tPA administration kits, which include order forms, inclusion and exclusion criteria, and the medication, the pharmacy placed the medication at the bedside.

A second ED nurse reads the order and administers the tPA bolus. Within minutes, the INR resulted at 4.9, an unequivocal contraindication to thrombolytic therapy. The outcome for this patient is catastrophic bleeding.  

Thrombolytic Therapy

In any emergency department, an acute stroke is an urgent medical event with complex institution-specific treatment protocols for eligible patients. Medications, such as thrombolytics, carry an increased risk of significant patient harm when used in error. The Institute of Safe Medication Practices (ISMP) classifies tPA a “high-alert” medication.  

Intravenous alteplase (IV) is the only approved treatment for acute ischemic stroke, but tenecteplase (TNK), an engineered plasminogen activator, is an alternative thrombolytic agent gaining favor. Delivery advantages and non-inferior trial results have driven TNK as a treatment choice for acute stroke. Of note, no definitive data on the efficacy of tPA versus TNK to treat ischemic stroke exists. Is tenecteplase administration a safer alternative?

What Is Driving the Shift in Care?

In early 2022, the Cleveland Clinic stopped using Alteplase® and started using TNKase® for thrombolysis within 4.5 hours of patients’ last known well time. 

There are administration complexities with alteplase that do not exist with tenecteplase. Tenecteplase is a newer drug and equivalent to alteplase, but it remains unclear if tenecteplase is more effective.  

Regardless of the thrombolytic, the best way to improve stroke treatment is to deliver the proper drug in an efficient and effective manner. For patients treated with tenecteplase, the drug is less expensive, easier to dose, and has less adverse bleeding. 

Thrombolytic Therapy Workflow Differences

Among the pharmacological differences in tPA, an engineered variant of the alteplase molecule, a vial of tenecteplase, costs much less than an equivalent dose of Alteplase.  

In 2000, the United States Food and Drug Administration (FDA) approved TNK 0.5 mg/kg intravenous bolus for treating acute myocardial infarction (MI) at the site of a platelet-rich coronary thrombosis.  

For ischemic stroke, alteplase is the only FDA approved intravenous (IV) thrombolytic. Fewer bleeding complications occurred at 0.25 milligrams per kilogram (mg/kg) with tenecteplase than alteplase. A randomized trial showed tenecteplase administration was associated with better reperfusion and clinical outcomes than alteplase.  

TNKase Dosing

For adult patients receiving tenecteplase within 4.5 hours of stroke symptoms, the dosing is 0.25 mg/kg (Max: 25 mg) IV or 0.4 mg/kg (Max: 40 mg) IV as a single dose. The recommended total dose should not exceed 50 mg. The cost of tenecteplase administration is $9,969. 

Activase® Dosing  

For adult patients receiving alteplase within 3 and 4.5 hours after the onset of stroke symptoms, the dosing is 0.9 milligrams per kilogram. Unlike tenecteplase, administration of Activase® is 10% of the total dose as an initial intravenous bolus over 1 minute. Ninety percent of the remaining dose infuses over 60 minutes. The total dose of Activase® must not exceed ninety milligrams. The cost of alteplase administration is $13,054.  

Post Dose Monitoring

With Activase®, nurses need to continue to watch for neurologic deterioration. Most protocols include vital signs Q15 minutes for the first hours after cessation of thrombolytic. Q30 minutes for 6 hours, then Q8 hours until 24 hours after the patient completed the infusion. Blood pressure control follows the same protocol.  

For TNKase® the required monitoring is continuous ECG for at least 90 minutes post infusing and visual assessment for bleeding, neurological changes Q 15 min x 2 hours, then Q 30 x 6 hours. Of note, angioedema is a potential life-threatening adverse effect unique to tenecteplase. Post monitoring protocols may vary per institution.  

The Bottom Line

Thrombolytics for the emergency treatment of stroke and myocardial infarction are FDA approved. With any high-alert medication, such as thrombolytic therapy, risk exists.  

These range from minor bleeding, hemorrhage (intracranial or systematic), genitourinary and gastrointestinal bleeding, and immunologic complications.  

For most patients, the benefits of prompt treatment and salvaged neurologic function can outweigh the risks.  

Decisions for thrombolytic therapy are based on the risks and benefits of each individual patient. Consult your institution’s specific policies and procedures on thrombolytic therapy and be cognizant of potential changes in drug therapy for acute stroke.  

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