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Lisinopril angioedema: Symptoms and treatment

Learn how lisinopril, a common ACE inhibitor, can trigger angioedema, with insights into symptom management and risk factors.
Keith Gardner, RPh, medical writer and reviewer for SingleCare
By | Updated on Sep. 24, 2024
Human feet: Lisinopril angioedema

Key takeaways

  • Angioedema is a potentially serious side effect of lisinopril (and other ACE inhibitors) and can occur at any time during treatment.

  • Symptoms of angioedema include swelling in the face, mouth, lips, or upper airway; more serious symptoms include swelling in the throat, making it difficult to breathe, or swelling in the gut, leading to abdominal pain, diarrhea, nausea, vomiting, or loss of appetite.

  • Symptoms usually resolve within one to five days without medical intervention. However, more serious symptoms, such as difficulty breathing, may require emergency medical care.

  • If experiencing symptoms of angioedema, stop taking lisinopril immediately and do not restart or take any other ACE inhibitor.

In this article:

Lisinopril is a generic drug commonly belonging to the angiotensin-converting enzyme inhibitors (ACE inhibitors) class of medications used to treat high blood pressure (hypertension). These medicines work by relaxing the blood vessels, enhancing blood flow, and allowing the heart to pump blood more effectively. Zestril, the brand name version of lisinopril, also helps increase life expectancy after a heart attack (myocardial infarction) and can improve symptoms in people with congestive heart failure.  ACE inhibitor therapy is considered an effective treatment and is well-tolerated by most people, leading to its being commonly prescribed. Still, adverse drug reactions, including a serious condition called angioedema, are possible when taking ACE inhibitors like lisinopril.

What is angioedema, and lisinopril-induced angioedema?

Angioedema is an allergic reaction that causes swelling in the deeper layers of the skin. Symptoms may include swelling of parts of the face, mouth, tongue, and upper airway. In very rare instances, swelling of the airway can prevent oxygen from reaching the lungs, leading to life-threatening situations. The intestines may swell, leading to abdominal pain, diarrhea, vomiting, and loss of appetite.

Angioedema can be classified as acute or recurrent. Acute events are generally mild and resolve within twenty-four hours without treatment. Recurrent angioedema can be chronic, recurring over weeks or months.

The onset of angioedema symptoms may be triggered by certain types of foods (e.g., shellfish, fish, nuts, eggs, or milk), exposure to sudden changes in temperature, or following insect bites or stings. This article will focus on drug-mediated reactions, specifically ACE inhibitors like lisinopril, that can lead to angioedema. Angiotensin‐converting enzymes are responsible, among other activities, for the breakdown of a substance called bradykinin in the body—the increased levels of bradykinin lead to inflammation by increasing blood flow, tissue permeability, and pain. Because bradykinin levels may increase when taking an ACE inhibitor, this increase is the likely explanation for ACE inhibitor‐induced angioedema.

The reported incidence rate of ACE inhibitor-induced cases of angioedema varies from 0.1% to 0.7% of all patients who take the drugs, meaning for every 1,000 people who take an ACE inhibitor, up to seven people exhibit the symptoms. According to the FDA label for Zestril, in clinical studies, 0.1% (one in one thousand) of patients reported angioedema as an adverse event. Notably, there was a higher incidence of case reports among African Americans. Other factors increasing the risk of angioedema include having experienced previous episodes of angioedema, smoking, and patients over the age of 65. 

Lisinopril-related angioedema typically develops within a few minutes of taking the drug and can occur anytime during the first weeks of therapy. According to the medical literature, in some cases, the adverse effects may occur weeks, months, and even years after initiating treatment. The angioedema symptoms usually resolve independently over a few days but may recur at any time. 

Angioedema from lisinopril symptoms

Angioedema is a rare adverse reaction that can occur when taking lisinopril that, in extreme cases, may be life-threatening. It is commonly characterized by facial, mouth, tongue, or upper airway swelling. Unlike many other food or drug allergic reactions, no hives or itching are typically associated with the swelling. Other symptoms may include: 

  • Rapid skin swelling
  • Swelling in the throat causing hoarseness or making it difficult to breathe
  • Swelling in the gut leading to abdominal pain, diarrhea, nausea, vomiting, or loss of appetite 

Lisinopril angioedema treatment

For non-severe cases of lisinopril-related angioedema, the recommendation is to discontinue taking the drug immediately. When side effects subside, patients should not retake lisinopril or any other ACE inhibitor due to the likelihood that it is a class effect. The prescribing healthcare professional may change to a different class of antihypertensive medication, such as angiotensin receptor blockers (ARBs) or a calcium channel blocker.

Common treatments for most allergic reactions include antihistamines, such as Benadryl (diphenhydramine), steroids (e.g., dexamethasone or prednisone), or epinephrine. Because lisinopril‐induced angioedema is not due to the excess release of histamine in the body, the use of these traditional antihistamine treatments has not proven to be helpful. In severe episodes of angioedema, fresh frozen plasma (FFP) may be an effective treatment. FFP contains enzymes that can metabolize the excess bradykinin. Clinical researchers are still exploring additional therapies for ACE inhibitors‐mediated angioedema.

The swelling from ACE inhibitor-related angioedema that causes upper airway obstruction is a critical situation that requires immediate medical attention. In severe cases, the patient may need a breathing tube inserted to maintain an open airway.

How long does angioedema from lisinopril last?

Symptoms of lisinopril-induced angioedema usually resolve as early as 24 hours after discontinuing the medication and typically require no medical intervention. In some more serious cases, the average time for full resolution may be closer to five days. Swelling symptoms that last longer than a few days could be due to another cause and should be checked by a healthcare professional.