Can you take Entresto with Lisinopril? The short, direct, and clinical answer is no. Taking Entresto (sacubitril/valsartan) with lisinopril—or any other ACE inhibitor—is strictly contraindicated. This combination poses severe, potentially life-threatening risks and should never occur without a required washout period under strict medical supervision.
The Core Danger: Why These Two Don’t Mix
The prohibition against combining Entresto and lisinopril is rooted in the mechanism of action of both drugs and a dangerously amplified side effect.
Risk of Angioedema: Both Entresto and lisinopril affect the body’s bradykinin system. Lisinopril is an ACE inhibitor, which prevents the breakdown of bradykinin. Entresto contains sacubitril, a neprilysin inhibitor, which also prevents bradykinin breakdown . Taking them simultaneously creates a synergistic effect, leading to a massive buildup of bradykinin. This significantly increases the risk of angioedema—rapid, severe swelling of the deeper layers of the skin, often around the eyes, lips, tongue, and throat. This swelling can obstruct airways and become fatal .
The Required Washout Period
If a patient is switching from lisinopril to Entresto, a mandatory 36-hour washout period is required . This means you must wait at least 36 hours after your last dose of lisinopril before you can take your first dose of Entresto. This gap allows the ACE inhibitor to clear from your system, minimizing the risk of angioedema .
Additional Risks of Dual RAAS Blockade
Even if angioedema is avoided, combining these drugs is dangerous because they both act on the renin-angiotensin-aldosterone system (RAAS). Entresto contains valsartan (an ARB), and combining an ARB with an ACE inhibitor like lisinopril for dual RAAS blockade is generally avoided . This combination can lead to:
- Severe Hypotension: Dangerously low blood pressure.
- Hyperkalemia: Excessively high potassium levels, which can cause irregular heartbeats and cardiac arrest .
- Acute Kidney Injury: Impaired kidney function .
Studies have shown increased rates of these serious adverse events when ACE inhibitors and ARBs are combined .
Who Should NOT Take Entresto
Beyond being actively on an ACE inhibitor, Entresto is contraindicated if you have:
- A history of angioedema related to ACE inhibitor or ARB use .
- Concurrent use of aliskiren in diabetic patients .
The Bottom Line for Patients
Do not take Entresto and lisinopril together.
- If you are prescribed Entresto, your doctor will instruct you to stop lisinopril and observe the 36-hour waiting period before starting the new medication.
- If you are on Entresto, never start lisinopril or any other ACE inhibitor.
This is a non-negotiable safety rule. Always provide your doctor and pharmacist with a complete and current list of all your medications to avoid this and other dangerous interactions .