Lisinopril Contraindications – When is lisinopril contraindicated for use?
Nearly every second, an adult in the U.S. has high blood pressure and is at risk for heart disease and stroke. (1) The American College of Cardiology and the American Heart Association recommend antihypertensive medication to everyone with systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg in several blood pressure readings, and those with hypertension and at high risk for atherosclerotic cardiovascular disease. (2)
Angiotensin-converting enzyme (ACE) inhibitors are frequently prescribed medications for blood pressure regulation; lisinopril is one of them.
Aside from the different clinical effects of medications, one of the factors that doctors consider when prescribing medication is the possible side effects and contraindications. Despite the proven positive effects in treatment, patients allergic to lisinopril or with a history of angioedema cannot use lisinopril. (3)
This article explains lisinopril contraindications and when and why lisinopril should not be used. Also, learn about the symptoms and when to call your doctor and ask for medical help.
When to Use Lisinopril?
Lisinopril decreases the production of angiotensin II in the body. Angiotensin II is a potent vasoconstrictor that tightens the blood vessels. When angiotensin II production is decreased, it helps blood flow to run smoothly through blood vessels and the heart to pump blood regularly. (3-4)
With this mechanism, lisinopril regulates blood pressure and prevents the damage that hypertension can cause to the different parts of the body, such as the brain, heart, blood vessels, kidneys, and others. When given with other medications, lisinopril is also approved for heart failure treatment and to improve survival after a heart attack. (3-4)
Who Shouldn’t Use Lisinopril?
Although lisinopril has been a well-established ACE inhibitor in doctors’ practice for high blood pressure regulation for over 30 years, not all patients can get the clinical benefit from it. Lisinopril is contraindicated in those who are hypersensitive, experience or have a history of angioedema, and those with diabetes who are on aliskiren treatment. If you are one of them, keep reading to find out why.
As with any other medication, some people might be allergic to lisinopril or other ingredients that the drug has. Those who used other ACE inhibitors before, such as enalapril, benazepril, captopril, ramipril, or others, or any other medication they were allergic to, might be allergic to lisinopril, as well. (4)
A drug may cause allergic reactions by any of the four types of hypersensitivity. Rash, cough, low blood pressure, headache, diarrhea, weakness, and dizziness, are some symptoms that could develop if you are allergic to any of the medication ingredients. (5)
You can consult the pharmacist about the ingredients that lisinopril contains.
Angioedema or a History of Hereditary or Idiopathic Angioedema
Angioedema is a reaction of our body to a specific trigger that results in swelling. In angioedema, the body fluid builds up in the deeper layers of the skin and mucous membranes (subcutaneous and/or submucosal layers of tissue). (6)
Different body parts can be affected, such as the arms, legs, or head. Face, lips, or neck can be affected too. However, when the larynx is involved, you may have breathing problems; in that case, angioedema becomes life-threatening. (6)
Hereditary angioedema (HAE) is when a body gene mutates and has a C1 esterase inhibitor deficiency. C1 esterase inhibitor is a protein in the body fluids that controls a C1 protein that protects the body from infections, together with other proteins. People with HAE usually inherit the deficiency from their parents. The cause of idiopathic angioedema is not known. (6-7)
Bradykinin’s increased level is the possible medical explanation of why some people who take ACE inhibitors experience angioedema. Bradykinin is a substance that our body produces and relaxes the arteriolar muscles, lowers blood pressure, and improves blood flow. The effect of the increased blood flow is warmth, redness, or swelling. In addition, bradykinin sensitizes the nerve endings that cause the pain. (8)
During the inflammation process, there is an increase in vasodilatation, permeability, and pain due to bradykinin’s role. Lisinopril inhibits the inactivation of bradykinin; the bradykinin levels elevate and build up fluids that, in the end, cause angioedema. About one-fifth of the patients on ACE inhibitors that experience angioedema would require airway intervention due to breathing problems. (8-9)
Due to possible life-threatening reactions, lisinopril is contraindicated in people with angioedema or a history of hereditary or idiopathic angioedema.
Lisinopril Co-administration with Aliskiren is Contraindicated in Patients with Diabetes
When lisinopril is co-administered with aliskiren in patients with diabetes, there is an increased risk of hypotension, hyperkalemia, and changes in renal function (including acute renal failure). (3)
Aliskiren is a direct renin inhibitor medication also used for high blood pressure treatment. It works similarly to lisinopril by affecting the chemicals that tighten blood vessels. (10)
When used together, lisinopril and aliskiren, these two medications block the renin-angiotensin system (RAS). Thus, the risk-benefit ratio does not support this dual RAS inhibition. Samir Mallat, in the meta-analysis conducted in 2013, based on the larger clinical trials, concluded that the dual RAS inhibition involving aliskiren had been reported in large trials to increase the risk of AEs with no clinical benefits. (11)
Lisinopril Recommended Dosage in Adults and Children
In those who are not contraindicated to take lisinopril, the doctor can prescribe it to adults and children over six years of age as approved:
The recommended initial dose to decrease blood pressure is 10 mg daily. The doctor will adjust the dose depending on individual responses to the therapy and might increase it to 80 mg daily as the maximal daily dose. In many patients, 20 to 40 mg once daily is usually the effective dose. (3)
Antihypertensive treatment may include more than one medication. Your doctor may prescribe antidiuretics if lisinopril cannot control the blood pressure as monotherapy. In the case of combo treatment for hypertension or heart failure, your doctor may decrease the lisinopril dose to achieve the optimal therapeutic effect. When initial hypertension treatment is together with a diuretic, starting with 5 mg of lisinopril is recommended. (3)
When used to reduce mortality in acute myocardial infarction, lisinopril’s initial dose is 5 mg daily for the first two days. As of the third day, the dose will increase to 10 mg and continue for at least six weeks. The initial therapy will be 2.5 mg in those with low blood pressure. Your doctor will decide how to continue the treatment, depending on your blood pressure. (3)
Children Over Six Years Old
The daily dose depends on the weight and glomerular filtration rate (> 30 mL/min/1.73m2). The starting dose in the pediatric population with hypertension is 0.07 mg per kg once daily. The dose should be adjusted and increased up to 0.61 mg per kg or up to 40 mg once daily. (3)
Lisinopril is not recommended:
- In children younger than six years;
- In children with glomerular filtration rate < 30 mL/min/1.73m2;
- In adults, in doses over 80 mg daily due to lack of effect increase. (3)
Side Effects of Lisinopril and Warnings When Using
If your doctor prescribed you lisinopril, you should be aware of the possible side effects that this medication may cause. Treatment with drugs that inhibit the renin-angiotensin system, such as lisinopril, may cause the following side effects, described in the Patient information sheet of lisinopril (3):
Fetal toxicity – Drugs that act on the renin-angiotensin system reduce the renal function of the fetus during the second and third trimesters, which may cause fetal death. It also negatively affects lung development, skeletal deformations, including the face, or hypotension. Therefore, if you use lisinopril and get pregnant, you should tell your doctor immediately and stop using the medication.
Angioedema – ACE inhibitors, including lisinopril, may cause keeping the fluids and swelling of the deeper layers of the skin on the arms, legs, and face, as explained above, but also in the intestinal mucosa followed by abdominal pain, with or without nausea and vomiting. Although challenging to diagnose, tell your doctor if you take lisinopril and have such symptoms.
Anaphylactoid Reactions – A life-threatening anaphylactoid reaction was reported by the patients undergoing desensitizing treatment with Hymenoptera venom and, in some patients, dialyzed with high-flux membranes.
Hypertension – Headache, dizziness, and cough can be associated with increased blood pressure while using lisinopril.
Hypotension – Lisinopril may cause hypotension, and patients with heart or renal diseases have increased risk. Hypotension and chest pain can occur in case of heart failure or acute myocardial infarction.
Renal impairment – Lisinopril may change renal function and cause renal failure.
Liver failure – It may begin with cholestatic jaundice or hepatitis and progresses to fulminant hepatic necrosis and sometimes death.
Hyperkalemia – Lisinopril may increase the levels of potassium in serum.
Read the Medication Guide carefully and ask your doctor for additional information. Report any adverse reaction to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088). (3-4)
Lisinopril has been used for many years in patients with hypertension, heart failure, or to improve survival after a heart attack. While most patients can use it safely, lisinopril is contraindicated in hypersensitive patients, those who have a history of angioedema, or are already on aliskiren therapy.
Read the Medication Guide and tell your doctor if you experience an allergic reaction to another ACE inhibitor or other medication. Don’t underestimate the symptoms and adverse reactions that might occur. Tell your doctor if you have any adverse events. Then, you or your doctor can report it to FDA and probably change the therapy.
Other antihypertensive medications can be used safely in those patients who cannot use lisinopril. Keep your doctor informed to find the best treatment option for your condition.
- Centers for Disease Control and Prevention, Facts about Hypertension, 2023 Jan, https://www.cdc.gov/bloodpressure/facts.htm
- American College of Cardiology, Harmonization of ACC/AHA and ESC/ESH BP/Hypertension Guidelines, 2022 Aug, https://www.acc.org/Latest-in-Cardiology/ten-points-to-remember/2022/08/22/16/48/Harmonization-of-the-ACC-AHA#:~:text=The%20ACC%2FAHA%20guideline%20recommends,DBP%2080%2D89%20mm%20Hg.
- Food and Drug Administration, Zestril® (lisinopril) tablets, for oral use, Prescribing Information, 2014 Dec, https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019777s064lbl.pdf
- MedlinePlus, Lisinopril, 2021 Feb, https://medlineplus.gov/druginfo/meds/a692051.html
- National Library of Medicine, Immediate Hypersensitivity Reactions, 2022 Aug, https://www.ncbi.nlm.nih.gov/books/NBK513315/
- National Library of Medicine, Angioedema, 2022 Aug, https://www.ncbi.nlm.nih.gov/books/NBK538489/
- MedlinePlus, C1 esterase inhibitor https://medlineplus.gov/ency/article/003353.htm
- National Library of Medicine, Physiology, Bradykinin, 2022 Jul, https://www.ncbi.nlm.nih.gov/books/NBK537187/#:~:text=Bradykinin%20plays%20a%20prominent%20role,in%20turn%2C%20increases%20blood%20flow.
- US Pharmacist, Cross-Reactivity of ACE Inhibitor–Induced Angioedema with ARBs, 2007 Feb https://www.uspharmacist.com/article/cross-reactivity-of-ace-inhibitorinduced-angioedema-with-arbs
- MedlinePlus, Aliskiren, 2021 Feb, https://medlineplus.gov/druginfo/meds/a607039.html#:~:text=Aliskiren%20is%20used%20alone%20or,can%20pump%20blood%20more%20efficiently.
- Samir G Mallat, Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence? Cardiovascular Diabetology volume 12, Article number: 108 (2013) https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-12-108