From the Research
Yes, Proton Pump Inhibitors (PPIs) can cause Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), though this is a rare adverse effect. The most recent and highest quality study, published in 2022 1, found that PPIs are associated with SIADH, with rabeprazole having the strongest association. This study analyzed reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and found that PPI-associated SIADH typically occurs in elderly patients, with a median time to onset of 22 days after PPI administration.
Key Points
- PPIs such as omeprazole, esomeprazole, pantoprazole, lansoprazole, and rabeprazole have been implicated in case reports of SIADH 2, 1.
- The mechanism appears to be related to the PPIs' ability to stimulate inappropriate release of antidiuretic hormone (ADH) from the posterior pituitary or to enhance ADH effects at the kidney level.
- SIADH typically presents with hyponatremia (low sodium levels), often when sodium drops below 130 mEq/L, causing symptoms like confusion, headache, nausea, and in severe cases, seizures or coma.
- Management typically involves discontinuing the PPI, fluid restriction, and sometimes sodium supplementation 3.
Risk Factors
- Advanced age
- Female gender
- Concomitant use of other medications that can cause SIADH (like SSRIs or certain diuretics)
- Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase of hypomagnesemia, which may also contribute to the development of SIADH 4.
Recommendations
- Healthcare providers should consider SIADH as a potential cause in patients on PPIs who develop unexplained hyponatremia.
- Evaluate patients by checking serum and urine osmolality and sodium levels.
- Discontinue the PPI and implement fluid restriction and sodium supplementation as needed.
- Monitor patients with risk factors more closely.