How often does long-term PPI therapy cause clinically significant hypomagnesemia?
EVIDENCE-BASED ANSWER:
Rarely. Proton pump inhibitors (PPIs) may be associated with decreases in serum magnesium laboratory values to below 1.6 to 1.8 mg/dL, especially when used concurrently with diuretics and loop diuretics (strength of recommendation [SOR]: C, disease-oriented outcomes based on cohort, case-control, and cross-sectional studies). Clinically significant or symptomatic hypomagnesemia (below 1.2 mg/dL) appears to be quite rare, however.
A comparison of the use of loop diuretics and thiazides by patients taking PPIs found that concurrent use of loop diuretics increased serum magnesium reduction (−0.08 mg/dL; 95% CI, −0.14 to −0.02), but thiazides didn’t. Numbers were small: Of the 45 participants taking both a PPI and a loop diuretic, only 5 had hypomagnesemia (OR=7.2; 95% CI, 1.7-30.8).3
RECOMMENDATIONS
In 2011, the US Food and Drug Administration (FDA) warned of a possible increased risk of hypomagnesemia in patients taking PPIs long-term. The FDA advisory panel recommended evaluating serum magnesium before beginning long-term PPI therapy and in patients concurrently taking diuretics, digoxin, or other medications associated with hypomagnesemia.6
