Sacubitril and Lisinopril: 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
Sacubitril
No brand names on record
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.
These two medicines should not be taken together. Lisinopril is an ACE inhibitor, and sacubitril (found in sacubitril/valsartan) works in a related way. When combined, they can raise your risk of a serious swelling reaction called angioedema, which can cause swelling of the face, lips, tongue, or throat and can make breathing hard.
Because of this risk, there needs to be a gap of at least 36 hours between stopping one and starting the other. The good news is your care team knows how to handle this safely by timing the switch correctly. Never start, stop, or change either medicine on your own. Talk with your doctor or pharmacist first.
Contraindicated combination. Concomitant use of an ACE inhibitor (lisinopril) with sacubitril/valsartan is contraindicated due to additive risk of angioedema. Neither agent's PK is the driver; this is a pharmacodynamic additive effect on bradykinin-mediated pathways.
- Direction: Increased risk of adverse effects (angioedema), not an efficacy change.
- Evidence: Theoretical/mechanistic, but severity is high enough to warrant an absolute contraindication.
- Management: Do not co-administer. Allow a washout of at least 36 hours between the last ACE inhibitor dose and initiation of sacubitril/valsartan (and vice versa). Monitor for oropharyngeal or facial swelling during any transition.
What happens
Increased risk of angioedema
Interaction Deep Dive
Because it raises the likelihood of adverse reactions such as angioedema, the simultaneous use of sacubitril/valsartan with an ACE inhibitor is contraindicated. A gap of at least 36 hours must separate the administration of an ACE inhibitor and sacubitril/valsartan12.
Why it happens (mechanism)
Additive adverse effects, including angioedema
How to manage this interaction
These two are not used together. When switching between an ACE inhibitor like lisinopril and sacubitril/valsartan, your care team builds in a washout period.
- Do not take both at the same time.
- A gap of at least 36 hours is needed between the last dose of one and the first dose of the other.
- Your prescriber will plan and time this changeover for you.
Keep taking your medicine exactly as prescribed, and do not stop or start either drug on your own. Ask your pharmacist or doctor before any switch, and seek emergency care right away if you notice swelling of the face, lips, tongue, or throat, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Sacubitril and Lisinopril together?
Lisinopril and sacubitril/valsartan should not be taken together because of the risk of serious swelling (angioedema); a gap of at least 36 hours is needed when switching. Let your doctor or pharmacist plan the changeover. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sacubitril and Lisinopril interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Sacubitril and Lisinopril interaction managed?
These two are not used together. When switching between an ACE inhibitor like lisinopril and sacubitril/valsartan, your care team builds in a washout period. Do not take both at the same time. A gap of at least 36 hours is needed between the last dose of one and the first dose of the other. Your prescriber will plan and time this changeover for you. Keep taking your medicine exactly as prescribed,… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sacubitril or Lisinopril 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 (2)
- Product Information: Zestril(R) oral tablets, lisinopril oral tablets. Almatica Pharma, Inc (per FDA), Pine Brook, NJ, 2017. DailyMed
- Product Information: ENTRESTO(TM) oral tablets, sacubitril valsartan oral tablets. Novartis Pharmaceuticals Corporation (per Manufacturer), East Hanover, NJ, 2015. DailyMed
Keep reading about Lisinopril
Keep reading about Sacubitril
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist