Lisinopril and Azilsartan Medoxomil: 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
Azilsartan Medoxomil
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.
Lisinopril and azilsartan (Edarbi) both lower blood pressure by working on the same body system, called the renin-angiotensin system. Lisinopril is an ACE inhibitor and azilsartan is an ARB. When you take two drugs that block this system at the same time, the effect can stack up too much.
This can cause your blood pressure to drop too low (leading to dizziness or fainting), raise your potassium levels, and put extra strain on your kidneys. Doctors usually avoid using both together for this reason. The good news is your care team can manage this. Please talk with your pharmacist or doctor before making any changes, and don't stop either medicine on your own.
Interaction: Combining lisinopril (ACE inhibitor) with azilsartan medoxomil (ARB, a prodrug hydrolyzed to active azilsartan) produces dual RAAS blockade. Neither drug alters the other's metabolism; this is an additive pharmacodynamic effect.
- Direction/effect: Increased risk of hypotension, syncope, hyperkalemia, and declining renal function including acute renal failure.
- Evidence: Established; supported by outcome trials and meta-analyses (notably in LV dysfunction and high-risk vascular/diabetic populations).
- Management: Generally avoid combination. If necessary, closely monitor blood pressure, serum potassium, and renal function (SCr/eGFR).
What happens
Increased risk of adverse events (ie, hypotension, syncope, hyperkalemia, changes in renal function, acute renal failure)
Interaction Deep Dive
Combining an ACE inhibitor with an angiotensin receptor blocker (ARB) to achieve dual blockade of the renin-angiotensin-aldosterone system has been linked to a greater frequency of adverse effects. Among patients who have documented atherosclerotic disease, heart failure, or diabetes accompanied by end organ damage, giving an ACE inhibitor together with an ARB produced a higher rate of hypotension, syncope, hyperkalemia, and altered renal function (acute renal failure included) when compared to using either drug by itself3. As a rule, this combination is best avoided, but if joint administration cannot be prevented, blood pressure, renal function, and electrolytes should be monitored carefully 4. A meta-analysis conducted in patients with left ventricular dysfunction found that adding an ACE inhibitor to ARB treatment raised the overall risk of adverse events that led to therapy being stopped, relative to ACE inhibitor treatment given alone 1.
Why it happens (mechanism)
Dual blockade of the renin-angiotensin-aldosterone system
How to manage this interaction
Doctors generally avoid using an ACE inhibitor (lisinopril) and an ARB (azilsartan) together because of the added risks. If your care team has decided you need both, that decision was individualized to you, so keep taking both exactly as prescribed unless told otherwise.
When these are used together, your team typically will:
- Check your blood pressure more closely.
- Monitor your kidney function and potassium levels with blood tests.
Let your pharmacist or prescriber know if you feel dizzy, lightheaded, faint, unusually weak, or notice changes in how much you urinate. Ask them any time you're unsure why you're on both.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A systematic review with meta-analysis involving 18,160 patients who had heart failure or left ventricular dysfunction, drawn from 9 randomized trials, showed that adding an angiotensin receptor blocker (ARB) to ACE inhibitor treatment was linked to a higher risk of adverse events that led to stopping therapy, compared with ACE inhibitor treatment by itself. Every patient had NYHA functional class II to IV heart failure, an ejection fraction of 45% or lower, or left ventricular dysfunction acutely following myocardial infarction. The agents included were losartan, candesartan, valsartan, irbesartan, and telmisartan. Follow-up ranged from 4 weeks to 41 months. The analysis found that combination therapy raised the risk of experiencing any adverse effect by 2.3%. The risk of hypotension rose by 1.1%, the risk of worsening renal function rose by 1%, and the risk of hyperkalemia rose by 0.6%. In contrast, the risk of angioedema or cough was not significantly different between the treatment groups. When a combination approach is required, patients should be closely monitored for possible adverse effects 1.
Common questions
Can I take Lisinopril and Azilsartan Medoxomil together?
Taking lisinopril and azilsartan together doubles up on the same blood pressure system and raises the risk of low blood pressure, high potassium, and kidney problems, so this combination is usually avoided. If your doctor has you on both, keep taking them as prescribed and expect closer monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Azilsartan Medoxomil interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Lisinopril and Azilsartan Medoxomil interaction managed?
Doctors generally avoid using an ACE inhibitor (lisinopril) and an ARB (azilsartan) together because of the added risks. If your care team has decided you need both, that decision was individualized to you, so keep taking both exactly as prescribed unless told otherwise. When these are used together, your team typically will: Check your blood pressure more closely. Monitor your kidney function and… 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 Azilsartan Medoxomil 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)
- Lakhdar R, Al-Mallah MH, & Lanfear DE: Safety and tolerability of angiotensin-converting enzyme inhibitor versus the combination of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker in patients with left ventricular dysfunction. J Card Fail 2008; 14(3):181-188.
- Product Information: Lotensin(R) oral tablets, benazepril HCl oral tablets. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2014. DailyMed
- Product Information: COZAAR(R) oral tablets, losartan potassium oral tablets. Merck Sharp & Dohme Corp. (per FDA), Whitehouse Station, NJ, 2011. DailyMed
- Product Information: EXFORGE oral tablets, amlodipine valsartan oral tablets. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2019. DailyMed
Keep reading about Lisinopril
Keep reading about Azilsartan Medoxomil
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