Lisinopril and Sacubitril and valsartan interaction
Lisinopril and Sacubitril and valsartan: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Lisinopril (Zestril) label · effective 2025-01-02
Zestril is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril).
Do not administer Zestril within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor [ see Warnings and Precautions (5.2)] .
Angioedema and Anaphylactoid Reactions Patients taking concomitant mTOR inhibitor (e.g. temsirolimus, sirolimus, everolimus) therapy or a neprilysin inhibitor may be at increased risk for angioedema. [see Drug Interactions (7.7 , 7.8)] .
Concomitant mTOR inhibitor or neprilysin inhibitor use may increase angioedema risk (7.7, 7.8)
Dual Blockade of the Renin-Angiotensin System (RAS) Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
From the Sacubitril and valsartan (ENTRESTO) label · effective 2026-07-06
ENTRESTO is contraindicated: in patients with hypersensitivity to any component in patients with a history of angioedema related to previous ACE inhibitor or ARB therapy [see Warnings and Precautions (5.2)] with concomitant use of ACE inhibitors.
Do not administer within 36 hours of switching from or to an ACE inhibitor [see Drug Interactions (7.1)] with concomitant use of aliskiren in patients with diabetes [see Drug Interactions (7.1)] Hypersensitivity to any component.
Concomitant use with ACE inhibitors.
ENTRESTO must not be used in patients with a known history of angioedema related to previous ACE inhibitor or ARB therapy [see Contraindications (4)] .
Dual Blockade of the Renin-Angiotensin-Aldosterone System Concomitant use of ENTRESTO with an ACE inhibitor is contraindicated because of the increased risk of angioedema [see Contraindications (4)] .
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.