Associations of proton pump inhibitors and hospitalization due to hyponatremia: A population-based case-control study

Small observational studies and case reports have indicated that proton pump inhibitors (PPIs) may cause hyponatremia. Whether there is a difference between the individual PPIs is yet unknown. Since PPIs are one of the most commonly prescribed groups of drugs, even a rare adverse reaction may have large implications. The objective was to study the association between PPIs and hospitalization due to hyponatremia.

This register-based case-control study was based on the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared to matched controls (n = 57,383). The association between newly initiated (≤90 days) and ongoing PPI use was explored using multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and socioeconomic factors.

Adjusted ORs (95%CI) for hospitalization due to hyponatremia, compared to controls, were for newly initiated: omeprazole 2.67 (2.37-3.01); pantoprazole 2.06 (1.32-3.19); lansoprazole 1.19 (0.72-1.94); esomeprazole 2.89 (2.21-3.79) and any PPI 2.78 (2.48-3.11). Only one individual had been newly initiated on rabeprazole and had been hospitalized due to hyponatremia. Adjusted ORs (95%CI) for individuals with ongoing treatment were for: omeprazole 1.04 (0.97-1.11); pantoprazole 0.81 (0.62-1.05); lansoprazole 0.90 (0.70-1.15); rabeprazole 3.34 (0.84-11.43); esomeprazole 1.12 (0.94-1.33) and any PPI 1.04 (0.98-1.11).

With the exception of lansoprazole, this study suggests an association between any newly initiated PPI-treatment and hospitalization due to hyponatremia. Ongoing PPI use was not associated with an increased risk.