Potential Long-Term Side Effects of Lisinopril

Lisinopril (Zestril) is used to treat high blood pressure and heart failure and to improve survival after a heart attack. It works primarily by blocking the activity of angiotensin-converting enzyme (ACE). As an ACE inhibitor, lisinopril widens blood vessels, causing the blood pressure to fall and allowing the heart to pump more effectively.

Lisinopril is a medication used to treat high blood pressure. (Image: LightFieldStudios/iStock/GettyImages)

Like all medications, lisinopril has potential side effects. Many begin shortly after initiating treatment. But some side effects occur primarily with long-term use or develop at any time during lisinopril therapy.

1. Dry Cough

Some people will develop a dry cough — "lisinopril cough" — while taking lisinopril. This side effect has been attributed to lisinopril's ability to inhibit an enzyme called kininase, which breaks down bradykinin. This leads to increased levels of bradykinin in various areas of the body, including the lungs.

Lisinopril cough develops in as many as 4 percent of people taking the medication, according to the Food and Drug Administration–approved prescribing information. It can occur at any time after beginning lisinopril, from a few hours after the first dose to many months after starting treatment. Lisinopril cough usually disappears within 1 to 2 weeks after stopping the medication.

2. Swelling (Angioedema)

Angioedema refers to swelling in certain areas of the body. It is caused by increased bradykinin in these areas.

When angioedema occurs in the mouth and throat, it can block the flow of air into the lungs. This is a potentially life-threatening condition that requires immediate medical attention. Angioedema of the intestines can cause abdominal pain, with or without nausea or vomiting.

Angioedema is a rare side effect of lisinopril. Like lisinopril cough, angioedema may occur at any time during treatment.

3. Decreased Kidney Function

Lisinopril sometimes causes deterioration of kidney function. In some instances, this occurs soon after beginning treatment, whereas at other times, it develops after long-term use.

Decreased kidney function is more likely in people with severe heart failure, pre-existing kidney disease or narrowing of the renal arteries, which supply blood to the kidneys. It is also more common when lisinopril is used in combination with diuretics — "water pills."

As kidney function decreases, urine production decreases and fluid begins to accumulate in the body. Regular blood tests are often obtained to monitor kidney function during lisinopril treatment. If kidney function deteriorates, it usually improves with stopping the medication.

4. Liver Injury

There have been rare reports of liver injury associated with lisinopril use. According to the National Institutes of Health, this injury has occurred at variable times after starting lisinopril therapy, ranging from 2 weeks to 2 years.

Jaundice, characterized by yellowish skin and eyes, indicates the presence of liver injury. Regular blood tests are often obtained to measure liver enzymes and function during lisinopril treatment. In most instances, lisinopril-related liver injury resolves with discontinuing the medication.

Warnings and Precautions

Lisinopril may cause an excessive decrease in blood pressure during times of dehydration or when sodium levels in the body are low. Contact your doctor if you have symptoms of low blood pressure, such as lightheadedness or dizziness when rising to the standing position.

Unless approved by your doctor, do not consume salt substitutes containing potassium while taking lisinopril, as they can lead to high potassium levels. Do not take lisinopril if you are pregnant, as it may be harmful to your unborn child.

See your doctor if you have a persistent dry cough. Seek prompt medical attention if you notice new-onset swelling of your extremities or torso, persistent abdominal pain, decreased urine or jaundice. Obtain immediate medical care if you notice any swelling in your head or neck, shortness of breath, severe weakness or persistent dizziness or lightheadedness. Also seek immediate medical care if you are producing minimal or no urine.

Reviewed by Mary D. Daley, M.D.

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