Can Tenecteplase (tPA, tissue plasminogen activator) cause angioedema?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

Tenecteplase can cause angioedema as a rare but serious adverse effect, and immediate discontinuation of the drug and prompt treatment are necessary if it occurs. Angioedema is a potentially life-threatening allergic reaction characterized by swelling of the face, lips, tongue, throat, and sometimes extremities. The risk of angioedema with tenecteplase is estimated to occur in less than 1% of patients receiving the medication 1. If angioedema develops after tenecteplase administration, prompt treatment with antihistamines, corticosteroids, and epinephrine may be required depending on severity, as outlined in the 2018 guidelines for the early management of patients with acute ischemic stroke 1.

Key Considerations

  • Airway management should be prioritized if there is any sign of respiratory compromise
  • The mechanism behind tenecteplase-induced angioedema likely involves the release of bradykinin due to the drug's effect on the fibrinolytic system, which can trigger inflammatory cascades leading to increased vascular permeability
  • Healthcare providers should monitor patients closely during and after tenecteplase administration, particularly in the first hour when most hypersensitivity reactions occur
  • Patients with a history of allergic reactions to other thrombolytic agents may have an increased risk of developing angioedema with tenecteplase

Management of Angioedema

  • Discontinue IV tenecteplase infusion and hold ACEIs
  • Administer IV methylprednisolone 125 mg
  • Administer IV diphenhydramine 50 mg
  • Administer ranitidine 50 mg IV or famotidine 20 mg IV
  • If there is further increase in angioedema, administer epinephrine (0.1%) 0.3 mL subcutaneously or by nebulizer 0.5 mL The 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction provides information on the dosage and patency rate of tenecteplase, but does not specifically address the risk of angioedema 1. However, the 2018 guidelines for the early management of patients with acute ischemic stroke provide more relevant information on the management of orolingual angioedema associated with IV alteplase administration, which can be applied to tenecteplase-induced angioedema 1.

From the FDA Drug Label

Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of TNKase (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Yes, Tenecteplase (tPA, tissue plasminogen activator) can cause angioedema 2.

From the Research

Angioedema and Tenecteplase

  • Tenecteplase, a tissue plasminogen activator (tPA), has been associated with angioedema, a swelling of the subcutaneous or submucosal layers of the skin or gastrointestinal tract 3.
  • Angioedema can occur due to increased levels of bradykinin as a result of the activation of the fibrinolytic pathway and contact activation system 3, 4.
  • The incidence of angioedema with tPA is estimated to be around 0.02% in patients with myocardial infarction or pulmonary embolism and 0.2% to 5.1% in patients with stroke 5.

Risk Factors and Treatment

  • Risk factors for tPA-associated angioedema include use of angiotensin-converting enzyme inhibitors, female gender, diabetes, and infarcts of the insula and frontal cortex 3, 6.
  • Treatment for angioedema typically involves supportive medications such as corticosteroids, antihistamines, and epinephrine 5, 6.
  • In severe cases, angioedema can cause life-threatening airway compromise, requiring intubation 7, 6.

Specific Cases and Studies

  • A case report described a 65-year-old man who developed angioedema after receiving tenecteplase for acute ischemic stroke, which was treated with steroids and antihistamines 3.
  • Another study reported a case of an 84-year-old woman who developed severe orolingual edema after receiving alteplase, requiring emergent intubation 7.
  • A review of 27 patients who experienced angioedema with tPA while on ACE inhibitor therapy found that most patients required a combination of supportive medications for management 6.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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