Can proton pump inhibitors (PPIs) cause hypernatremia?

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Last updated: July 4, 2025View editorial policy

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From the Guidelines

Proton pump inhibitors (PPIs) are not typically associated with causing hypernatremia. PPIs like omeprazole, esomeprazole, pantoprazole, lansoprazole, and rabeprazole work by blocking the hydrogen-potassium ATPase enzyme system in gastric parietal cells, reducing stomach acid production. While PPIs can cause various side effects and electrolyte disturbances, hypernatremia (elevated sodium levels in the blood) is not a commonly reported adverse effect, as seen in the review by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1. PPIs are more frequently associated with hyponatremia (low sodium), hypomagnesemia, and hypocalcemia through various mechanisms. The electrolyte imbalances typically associated with PPIs develop gradually and are more common with long-term use (typically months to years). Some key points to consider when prescribing PPIs include:

  • Using the minimum dose required to treat symptoms
  • Avoiding use for more than 12 weeks without an underlying chronic disease or risk factors
  • Monitoring for potential side effects such as Clostridium difficile infection, hypomagnesaemia, and bone loss/fractures, as noted in the European Heart Journal review 1 If a patient taking PPIs develops hypernatremia, other causes should be investigated, such as dehydration, diabetes insipidus, excessive sodium intake, or other medications. Patients on PPIs should have electrolytes monitored periodically, especially if they are elderly or taking other medications that affect electrolyte balance. It is essential to weigh the benefits and risks of PPI use, particularly in older adults, and to consider alternative treatments when possible, as recommended by the European Society of Cardiology working group on cardiovascular pharmacotherapy 1.

From the Research

Proton Pump Inhibitors and Hypernatremia

  • There is no direct evidence in the provided studies that proton pump inhibitors (PPIs) cause hypernatremia 2, 3, 4, 5, 6.
  • The studies mention that PPIs are associated with various electrolyte disturbances, including hypomagnesemia, hypocalcemia, hypophosphatasemia, hypokalemia, and hyponatremia, but not hypernatremia 2, 3, 4.
  • One study notes that hyponatremia is an extremely rare complication of PPI therapy, thought to result from inappropriate ADH secretion 3.
  • The available evidence suggests that PPIs are associated with a number of nonkidney adverse health outcomes and several untoward kidney outcomes, including acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, and kidney failure 4, 6.
  • However, none of the studies provide evidence of a link between PPI use and hypernatremia 2, 3, 4, 5, 6.

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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