Lisinopril and Alteplase, Recombinant: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lisinopril
Alteplase, Recombinant
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Here's what's going on. Alteplase (Activase) is a clot-busting drug given by IV, usually in the hospital for a stroke or heart attack. Lisinopril is a blood pressure medicine (an ACE inhibitor). When these two are used together, there's a higher chance of a reaction called orolingual angioedema, which means swelling of the lips, tongue, or throat.
This can happen quickly, sometimes within about 2 hours of the alteplase infusion. The good news is that this is well known to hospital teams. They watch closely for any swelling during and after the infusion and can treat it right away if it happens. If you take lisinopril, make sure your care team knows.
Effect: Increased risk of orolingual angioedema when alteplase is given to a patient on an ACE inhibitor (lisinopril).
Mechanism: Additive bradykinin elevation. Alteplase increases bradykinin production; ACE inhibitors reduce bradykinin degradation, so kinin-mediated angioedema risk rises. Neither drug is a prodrug here.
Onset: Rapid (case reports up to 2 hours post-infusion). Evidence: Established. Severity: Major.
- Monitor closely during and for several hours after infusion for lip/tongue/oropharyngeal swelling.
- If angioedema occurs, treat with antihistamines, corticosteroids, and/or epinephrine per protocol.
- Consider discontinuing the alteplase infusion.
What happens
An increased risk of orolingual angioedema
Interaction Deep Dive
Caution is warranted when alteplase is given to individuals taking ACE inhibitors. In patients with acute ischemic stroke treated with alteplase alongside concurrent ACE inhibitors, a heightened risk of orolingual angioedema has been reported234. Case reports describe angioedema developing as long as 2 hours following the alteplase infusion. Those receiving an alteplase infusion should be observed carefully both during administration and for several hours afterward for indications of orolingual angioedema. Should orolingual angioedema develop, suitable treatment (namely antihistamines, steroids, or epinephrine) should be started, and stopping the alteplase infusion should be considered1.
Why it happens (mechanism)
Increase in bradykinin production by alteplase; decrease in bradykinin breakdown by ACE inhibitors
How to manage this interaction
This is managed in the hospital setting. Alteplase is given by your medical team, so the main step is making sure they know you take lisinopril.
- Keep taking lisinopril as prescribed unless your prescriber tells you otherwise, and tell any emergency or hospital team about it.
- Your care team will watch you closely during and for several hours after the alteplase infusion for any swelling of the lips, tongue, or throat.
- If swelling occurs, they can treat it quickly with medicines like antihistamines, steroids, or epinephrine, and may stop the infusion.
If you notice tongue or mouth swelling or trouble breathing, alert the staff immediately.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) A 58-year-old man taking a benazepril/amlodipine combination experienced orolingual angioedema within 5 minutes of finishing intravenous alteplase given for acute stroke. Head CT, erythrocyte sedimentation rate, immunoglobulin E, and CBC with differential showed no abnormalities. An anaphylactic reaction was considered unlikely because the airway remained uncompromised and hemodynamic measures were stable. The patient received dexamethasone and a histamine antagonist, and the symptoms cleared entirely over the following 48 hours 2.
b) In a prospective study of patients given alteplase for stroke (n=120), the total incidence of orolingual angioedema was 1.7% (n=2/120; 95% confidence interval (CI), 0.2% to 5.9%), with a 5% (n=1/19) incidence among patients concurrently taking ACE inhibitors versus a 1% (n=1/101) incidence in those not taking ACE inhibitors (p=0.1). In both patients who developed orolingual angioedema, it appeared bilaterally and within 30 minutes following the alteplase infusion. In the patient concurrently receiving an ACE inhibitor, the orolingual angioedema was severe. CT results ruled out lingual hematoma, and both patients had infarction affecting the insular region. Both patients were managed with steroids and antihistamines, and their symptoms resolved gradually. A separate study of stroke patients with alteplase-associated angioedema and concurrent ACE inhibitor use was assessed. Across both studies, an elevated risk of alteplase-induced angioedema was found in patients taking ACE inhibitors (odds ratio, 37; 95% CI, 8 to 171; p less than 0.001) 3.
c) In a prospective study of patients given alteplase for acute ischemic stroke (n=176), the total incidence of orolingual angioedema was 5.1% (n=9/176; 95% confidence interval (CI), 2.3% to 9.5%). Among those who developed orolingual angioedema, 7 patients were taking an ACE inhibitor (lisinopril, n=4; cilazapril, n=1; enalapril, n=1; ramipril, n=1), yielding a relative risk (RR) of 13.6 (95% CI, 3 to 62.7) for angioedema development in patients taking ACE inhibitors. In most instances, the angioedema was mild, unilateral, and arose contralaterally to the ischemic hemisphere. Patients received histamine antagonists and steroids, and symptoms resolved over 1 to 24 hours. Analysis using the Alberta Stroke Program Early CT Scale (ASPECTS) score also showed a higher risk (RR 6.4 (95% CI, 1.4 to 30)) of orolingual angioedema in patients with infarction involving the insula and anterior frontal cortex regions 4.
Common questions
Can I take Lisinopril and Alteplase, Recombinant together?
Combining alteplase with lisinopril raises the risk of rapid swelling of the lips, tongue, or throat (angioedema); the hospital team will monitor closely and can treat it promptly. Make sure your care team knows you take lisinopril. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Alteplase, Recombinant interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Lisinopril and Alteplase, Recombinant interaction managed?
This is managed in the hospital setting. Alteplase is given by your medical team, so the main step is making sure they know you take lisinopril. Keep taking lisinopril as prescribed unless your prescriber tells you otherwise, and tell any emergency or hospital team about it. Your care team will watch you closely during and for several hours after the alteplase infusion for any swelling of the lips… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Lisinopril or Alteplase, Recombinant need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: ACTIVASE(R) IV injection, alteplase IV injection. Genentech,Inc, South San Fransisco, CA, 2005.
- Rafii MS, Koenig M, & Ziai WC: Orolingual angioedema associated with ACE inhibitor use after rtPA treatment of acute stroke. Neurology 2005; 65(12):1906-. PubMed
- Engelter ST, Fluri F, Buitrago-Tellez C, et al: Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke. J Neurol 2005; 252(10):1167-1170. PubMed
- Hill MD, Lye T, Moss H, et al: Hemi-orolingual angioedema and ACE inhibition after alteplase treatment of stroke. Neurology 2003; 60(9):1525-1527. PubMed
Keep reading about Lisinopril
Keep reading about Alteplase, Recombinant
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