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Lisinopril and Angioedema: A Life-Threatening Side Effect

Serious lisinopril side effects can occur after many years. Doctors may miss the diagnosis if lisinopril and angioedema affect the abdomen.

Lisinopril is the most frequently prescribed blood pressure pill in the United States. At last count, about 20 million Americans take this ACE (angiotensin converting enzyme) inhibitor daily. We estimate another 20 million people take a medicine containing an ACE inhibitor. That makes 40 million people taking this kind of medicine to control hypertension. Such drugs work quite well for most people. Except for a nasty cough, ACE inhibitors usually don’t cause intolerable side effects. For some people, however, there is one complication of ACE inhibitor medicines that is life threatening. That adverse reaction is called ANGIOEDEMA. Most people have no idea what it is. Keep reading to learn why lisinopril and angioedema is so scary.

A Delayed Lisinopril and Angioedema Reaction Surprises Pharmacist:

Q. I am a pharmacist and had taken lisinopril for over 12 years before I had an angioedema attack. About 8:00 PM, I started having allergic symptoms. By 10:00 PM, my face was swelling, and I couldn’t talk.

I rushed to the nearest hospital emergency room and was immediately diagnosed with angioedema. They started a steroid IV and about midnight I was on my way to recovery. I was discharged the next morning after being in the ICU overnight.

Despite my pharmacy education, I couldn’t imagine that such a delayed reaction (12 years!) could occur. This must be emphasized during patient counseling.

A. Thank you for sharing your scary story. Health professionals should always warn about angioedema (swelling of the mouth, lips and throat). It can also occur in the digestive tract and cause bloating, abdominal pain and obstruction. As you discovered, such complications can occur unexpectedly after years of safe treatment.

Lisinopril and Angioedema Could Be Deadly:

Q. Thank you for writing recently about lisinopril and angioedema. My late husband took lisinopril for over 16 years for high blood pressure. He died suddenly when his throat closed up. Although he had many symptoms leading up to this fatal episode, the doctor did not attribute them to lisinopril. I hope others are saved by the information you shared.

A. We are so sorry to learn about your husband. Angioedema can come on suddenly, even after taking an ACE inhibitor like lisinopril safely for years. Swelling of the lips, mouth, tongue or throat are signals of this reaction and can quickly become life threatening.

Although physicians have known about lisinopril and angioedema since the early 1990s (American Journal of Emergency Medicine, July 1992), they don’t always recognize it (Annals of Pharmacotherapy, April 2022). That’s why people taking lisinopril to control their blood pressure should inform themselves.

When Your Tongue Swells…It’s Could be Angioedema!

Q. I have been on lisinopril for at least five years and had no problems until today. I took my medicine around 2 pm, and by 2:30, my tongue had swollen so much that I had to hold it down with my finger to get a breath.

When I called my sister, she rushed me to the ER. As soon as I said I was on lisinopril, the ER doctor knew exactly what it was and administered an IV medication to stop the swelling.

Before starting the IV, the doctor asked me if I would agree to being intubated if the med did not work. I said yes, as a tear rolled down my cheek and I asked my sister to call my son.

I was very scared and will forever be grateful to the ER team that quickly diagnosed the problem and got it under control. I was discharged within four hours, more than a little shaken. No more lisinopril for me.

A. What you experienced is called angioedema. It involves the buildup of fluid in the lips, tongue or throat and can lead to life-threatening blockage of the airways. What makes this adverse reaction so challenging is that it can occur even after taking the drug safely for years.

One class of medications that is especially likely to trigger this reaction is called ACE (angiotensin converting enzyme) inhibitors. This includes drugs like benazepril (Lotensin), enalapril (Vasotec), lisinopril (Zestril) and quinapril (Accupril).

Although angioedema is considered a relatively rare side effect, tens of millions of people take an ACE inhibitor blood pressure medicine. It can also affect the intestines, a complication that is difficult to diagnose.

Abdominal Angioedema:

I have a relatively small number of good friends who I play tennis with. It’s usually under a dozen. The other day I was playing with Adam, Reinhard and Dave. All three commented that they had been diagnosed with abdominal angioedema after reading one of our newspaper columns at this link. Prior to seeing that article, they had all been suffering with very unpleasant and severe gastrointestinal symptoms that had not been diagnosed or treated successfully.

Once they learned about ACE inhibitor-related abdominal angioedema, they were able to get a correct diagnosis and a different blood pressure treatment. Their symptoms disappeared. Bottom line, three out of a dozen tennis players is not a rare complication. Of course this could just be the bizarre luck of the draw…or it could be that abdominal angioedema is not as rare as health professionals think.

To learn more about this dangerous condition as well as other hypertension treatments, you may wish to consult our eGuide to Blood Pressure Solutions. This online resource can be found under the Health eGuides tab.

Angioedema: A Mysterious Side Effect

There is a commercial that is running quite frequently these days. It is for a combination medication called Entresto (sacubitril/valsartan). While not exactly an ACE inhibitor, this medicine does impact the the angiotensin receptor. I won’t overwhelm you with the pharmacology of such drugs. If you are interested you can read about it at this link.

The ads for Entresto promote the idea that this drug:

“…helps improve your heart’s ability to pump blood to the body and with a healthier heart there’s no telling where life may take you.”

People in Entresto commercials are seen in active scenes such as hiking, fishing off a speed boat, sailing in the ocean and kayaking on a lake. The message is clearly that this drug will keep you vigorous, smiling and doing the things you love.

Then comes the message about side effects:

“The most serious side effects are angioedema, low blood pressure, kidney problems or high blood potassium.”

What the commercial does not reveal and what the FDA does not require is a description of angioedema. That worries us because the average patient may not know what symptoms to be alert for with angioedema. That is as true with Entresto as with ACE inhibitors like lisinopril. Doctors may not warn patients about lisinopril and angioedema or Entresto and angioedema. And pharmacists may assume it’s too rare to worry people about.

Lisinopril and Angioedema–a VERY Serious Side Effect:

The best way to understand angioedema is by reading what readers of our syndicated newspaper column and visitors to this website have experienced:

This person took lisinopril safety for over a decade. Then angioedema struck suddenly:

Q. I was prescribed lisinopril for high blood pressure over 10 years ago. It worked great with no side effects until recently. At first, I just noticed a little swelling in my face. Then my lips started swelling too. When my tongue swelled up, I was transferred to the ER by ambulance.

They treated me with an epinephrine injection and kept me overnight for observation. I was surprised that I could develop such a bad reaction after 10 years. You would think that such a serious side effect would have showed up much earlier. The ER doctor said it can happen after one day or after 20 years.

Do people know this?

A. Angioedema (swelling of the mouth, tongue or throat) can be a life-threatening reaction to “pril”-type blood pressure drugs. This category includes benazepril, captopril, enalapril, lisinopril and quinapril. Swelling of the tongue or throat requires immediate emergency medical treatment.

Abdominal Angioedema:

There is another kind of angioedema that can occur in the digestive tract. The same blood pressure medications can cause abdominal obstruction. This kind of swelling can lead to bloating and severe stomach pain and cramping. Such an adverse drug reaction can be hard to diagnose and is also life threatening. We offer more information about this reaction below.

We fear that patients are not always warned about angioedema. People should be warned that it can occur unexpectedly, even after many years of treatment.

Angioedema: A Delayed Reaction or Sudden Onset!

Q. I took lisinopril for three days and had an angioedema reaction. Luckily, the doctors in the emergency room diagnosed it quickly. They said they see this kind of reaction from lisinopril quite often.

This is one of the most frightening experiences I’ve ever had. My throat swelled shut. They pumped me full of steroids and kept me overnight for observation. The specialist I saw afterwards said he also sees this pretty often.

A. Most people tolerate lisinopril reasonably well. The most common side effect is a persistent cough that does not respond to treatment. It can be incredibly disruptive and keep people awake at night. Here is a link to one of our many articles on lisinopril cough:

Why Don’t Doctors Recognize Lisinopril Cough?
Why do so many doctors ignore the cause of a lisinopril cough? It would be as if a mechanic ignored the check engine light on your dashboard. It is NOT OK!

The angioedema complication you experienced is indeed potentially life threatening, as it can interfere with breathing.

Here is another report from a reader:

Q. My brother took lisinopril for nearly three years to lower his blood pressure. It did make him cough, but that didn’t bother him too much.

One morning, he woke up with his tongue so swollen he couldn’t keep it inside his mouth. He went to the ER and they called emergency triage.

The ER doctor came out, rushed him into the ER, stripped his clothes off on the way and gave him epinephrine. He said if he had been five minutes later, he might not have lived.

I’ve never had that kind of reaction, luckily. When I took Vasotec, though, it caused an awful cough.

Call 911 if Lisinopril and Angioedema Occur:

A. Your brother was smart to get to the emergency department in time. He experienced angioedema, a rare but life-threatening reaction to ACE inhibitor blood pressure medicines like lisinopril.

Symptoms of Angioedema:

NEVER ignore the following symptoms:
  • Swelling around the face including lips, eyes, eyelids or cheeks
  • Enlarged tongue, swelling in the mouth or throat
  • Difficulty speaking or swallowing, hoarseness,
  • Difficulty breathing, wheezing
  • Hives, welts or large red patches on the skin that may itch
  • Swelling of the hands, feet or genitals

Do not waste a moment if such symptoms occur. Call 911 immediately and make sure they know if you were taking an ACE inhibitor like lisinopril. By the way, drugs that end in “pril” are almost always in this class of medications. Here is a list of such drugs:

Benazepril (Lotensin)
Captopril (Capoten)
Enalapril (Vasotec)
Fosinopril (Monopril)
Lisinopril (Prinivil, Zestril)
Moexipril (Univasc)
Perindopril (Aceon)
Quinapril (Accupril)
Ramipril (Altace)
Trandolapril (Mavik)

Stories from Readers About Lisinopril and Angioedema:

Fred in Lodi, California shared a similar story:

“My roommate was prescribed lisinopril. Two days later she complained of swelling in her throat and tongue.

“I took her to the emergency room. They treated her with Benadryl, although she is allergic to it. Her throat swelled but they were able to get the breathing tube inserted in time.

“She was kept in a drug-induced coma for 7 days and was on a ventilator for 15 days before they did a tracheotomy. A week later they put a feeding tube in for her to come home. After 36 hours she was back in the hospital.”

David also had a close call:

“I had a knee replaced. Once back home, I had an allergic reaction to lisinopril. I had been taking it for over 10 years.

“My tongue and throat started swelling one night. I called my doctor and was told to use Benadryl. It did not help. I was rushed to hospital and had a tube put down my nose to help my breathing because my throat had swollen too much. A couple days later I woke up in the ICU. That was a scary few days for my family.”

A “Concerned American” reported this reaction:

“I just took my first dose of lisinopril last night. This morning I woke up with swollen hands. My neck, chest and arms look red like I was badly sunburned. I called the pharmacist and he told me that I am allergic to it. I cannot believe that one dose caused this much swelling and redness.”

Lisinopril and Angioedema of the Abdomen:

Most health professionals should know about angioedema and the symptoms we have described above. What many may not realize, however, is that angioedema can also occur in the abdomen.

It can be hard to diagnose, as this reader reports:

“I was put on lisinopril for high blood pressure in January. That month I experienced severe stomach cramping and vomiting. I was rolling on the floor in agony. The doctor said it was most likely the flu but started me on two different antibiotics in case it was bacterial.

“A few weeks later I had another attack with severe stomach cramping and vomiting. I went to the ER, where I was given IV pain meds. A CT scan showed small intestine inflammation partially blocking off my bowel. I was sent home but returned the next day with pain that was a 10 on a 10-point scale. The doctor said that all the tests had been done and there was nothing he could do. I was sent home with pain medication.

“A few weeks later I was admitted to the hospital with increased small intestine inflammation and another blockage. I vomited and dry-heaved for 12 hours. Four days later, they released me with no definitive diagnosis.

“I was told most likely I had Crohn’s disease, but a colonoscopy was negative for Crohn’s. I underwent extensive tests, including endoscopy, and all were negative. None of the doctors made a connection with the drug lisinopril.

“After two months of missing work, three more ER visits and untold suffering, I found several other people who reported similar symptoms connected to lisinopril. I stopped the medication and have not had another attack. If you look on PubMed you can see reports on lisinopril and intestinal angioedema, but doctors don’t think to connect this with lisinopril because it is not listed as a common side effect.”

LB in Maryland was initially misdiagnosed:

“I went to the ER and they told me my discomfort was caused by gas. The third time I passed out. The ambulance had to take me to the hospital.

“Finally I had a CT scan and the radiologist said to take me off lisinopril because it causes intestinal swelling. From my CT you could see the intestinal swelling. The doctors thought it was Crohn’s disease.”

NG also had a close call:

“I too had been experiencing a lot of mysterious abdominal pain after switching the brand of lisinopril I was taking. In fact, I endured months of abdominal attacks that came with ‘allergic-type’ reactions.

“Finally, I had to go to the ER because of an anaphylactic reaction. An allergist listened carefully and told me that it could be from the lisinopril. It is two days since I took lisinopril. I have no abdominal pain at all, although I have not been pain free for 5 months. I am so grateful for an observant doctor.”

James says “lisinopril has been trying to kill me:”

“About a month ago I discovered my BP medicine (linisopril) has been trying to kill me for the last 8 to 10 years. After 3 colonoscopies, 3 endoscopies, gallbladder scans, etc., I was told to learn to live with it. I suffered acute abdominal pain for the last ten years. BP 250/150 and as low as 80/44.

Small intestine angioedema sucks. In the town where I live, not one medical person ever heard of angioedema of the small intestines. Within 24-48 hrs of stopping my BP medicine, symptoms subsided. A month after stopping linisopril I still have no symptoms.”

Lisinopril and Angioedema of the Intestines Is Hard to Diagnose:

When people complain about amorphous abdominal discomfort, many doctors throw their hands up in despair. That’s because a lot of things can contribute to acute or chronic abdominal pain, cramping, nausea, vomiting, bloating and diarrhea.

When a patient complains of severe or excruciating belly pain while taking an ACE inhibitor, angioedema should be part of the “differential” diagnosis. In other words, doctors should consider it high on the list of potential problems causing the distress. Other kinds of medications can also trigger this reaction.

ACE Inhibitors and Cough:

Vasotec (enalapril) is also an ACE inhibitor. All such drugs may cause uncontrollable cough in susceptible people. We have lots of stories at these links:

Misdiagnosed Cough from Hell Makes Life Miserable

Why Do So Many Doctors Ignore Obvious Drug Side Effects?

Valsartan (Diovan) Side Effects Include Terrible Cough!

You can learn more about the pros and cons of various classes of medicine to treat hypertension and some nondrug options in our eGuide to Blood Pressure Solutions. This online resource can be found at this link.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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Citations
  • Rees RS et al, "Angioedema associated with lisinopril." American Journal of Emergency Medicine, July 1992. DOI: 10.1016/0735-6757(92)90010-u
  • Whitehead WJ & Reid JM, "Underreported risk of lisinopril-induced angioedema in a veteran population." Annals of Pharmacotherapy, April 2022. DOI: 10.1177/10600280211032404
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