Can Entresto (sacubitril/valsartan) cause hypernatremia?

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Last updated: July 6, 2025View editorial policy

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From the Research

Entresto (sacubitril/valsartan) is not typically associated with causing hypernatremia, and instead, tends to increase sodium excretion, making it an unlikely cause of elevated sodium levels. The medication works through a dual mechanism: sacubitril inhibits neprilysin, which increases levels of natriuretic peptides that promote sodium excretion, while valsartan blocks angiotensin II receptors, reducing sodium reabsorption in the kidneys 1. This is supported by a study published in 2023, which found that Entresto increased fractional sodium excretion in a porcine model of partial nephrectomy 1.

Some key points to consider when evaluating the relationship between Entresto and hypernatremia include:

  • The medication's mechanism of action, which promotes sodium excretion rather than retention
  • The lack of evidence suggesting a direct link between Entresto and hypernatremia
  • The importance of monitoring electrolytes in patients taking Entresto, especially during initiation and dose adjustments
  • The need to investigate other potential causes of hypernatremia, such as dehydration, excessive sodium intake, or other medications, if it occurs in a patient taking Entresto

It's also worth noting that Entresto has been associated with hyponatremia (low sodium levels) in some cases, as reported in a study published in 2020 2. However, this does not necessarily imply a causal relationship between Entresto and hypernatremia.

Overall, based on the available evidence, Entresto is not likely to cause hypernatremia, and any instances of elevated sodium levels in patients taking this medication should be investigated for other underlying causes 3, 4.

References

Research

Protective effect of sacubitril/valsartan (Entresto) on kidney function and filtration barrier injury in a porcine model of partial nephrectomy.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2023

Research

Sacubitril/Valsartan (Entresto®)-Induced Hyponatremia.

Journal of pharmacy practice, 2020

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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