Skip to main content

Entresto (Sacubitril/​Valsartan) & Angioedema

    Basic Details
    Last Updated
    Friday, March 8, 2024
    Original Posting Date
    Health Outcome(s)
    Drug and Outcome Analysis
    Meets requirements of FD&C Act Sec 505(o) prior to requiring a PMR
    Regulatory Determination / Use

    On July 7, 2015, sacubitril/valsartan (SV) was approved for the treatment of heart failure in patients with systolic dysfunction. Excess risk of angioedema, a rapid-onset, transient, potentially life-threatening swelling of the tongue, lips, mouth, throat, nose, and other parts of the face, has been described among users of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor/neprilysin inhibitors (ARNI) and angiotensin receptor blockers (ARB). Combining ACEIs and ARNIs has been shown to be associated with a greater risk of angioedema compared to ACEIs use alone.

    Therefore, due to the potential higher risk of angioedema when combining ARNI (sacubitril) and ARB (valsartan), compared to the use of sacubitril or valsartan alone, FDA compared the incidence of angioedema (serious and non-serious events) among the users of SV, and other drug classes indicated for heart failure, such as ACEIs, ARBs, β-blockers and digoxin in the Sentinel Distributed Database (SDD).

    No increased risk of angioedema was identified among SV new users compared with ACEI or ARB users. However, there was an increased risk of angioedema among SV users who had recently switched from an ACEI or ARB compared with SV new users. As the labeling was consistent with the study results, FDA determined no additional regulatory action is needed at this time.