Dr. Reed is an acute medicine clinical pharmacy specialist at the Captain James A. Lovell Federal Health Care Center in North Chicago, Illinois. Dr. Mok is a clinical pharmacy specialist at the Cheyenne VA Medical Center in Wyoming.
Author disclosures The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
One of the most widely prescribed classes of medications, PPIs are often regarded as safe and effective and therefore continued as long-term therapy. Results of this study showed an association of PPI use and hypomagnesemia—thereby adding to the literature. Results for the secondary objective suggest that the association does not necessarily depend on PPI dose, but, given that a statistical analysis of the difference between the case and control groups was not conducted, the statistical significance is unknown.
Although the hypomagnesemia rate remains undetermined, the results of this NNH study suggest a rate higher than previously proposed. Other investigators have estimated the rate of PPI-associated hypomagnesemia at 1%, which does not correlate well with the NNH often calculated in this study. For 2 possible reasons, the poor correlation may be attributable to underreporting of hypomagnesemia: Magnesium levels are not commonly checked with a basic metabolic panel, and many patients who are mildly hypomagnesemic remain asymptomatic.
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Future research directions include determining whether the risk for hypomagnesemia is related to patient status (eg, inpatient vs outpatient) and performing statistical analyses on the secondary objective to determine the clinical significance of potential risk factors. Other research directions might involve assessing PPI discontinuation rates in a hypomagnesemic population and assessing outcomes such as hospitalizations and AEs (eg, seizure, tetany, arrhythmia).
Limitations
This study had several limitations. First was the overall design. Study results described only a potential association of PPI use and hypomagnesemia, not definitive cause and effect. Results also depended on an assumed, previously reported rate of PPI-associated hypomagnesemia and a rate of exposure to PPIs, as these data were taken into account in the overall study design. In addition, patient adherence to prescribed therapy and accuracy of medication history were assumed from the medication and dispensing history, as not all medications obtained outside the Lovell FHCC were accurately documented. There also was an external validity limitation in that older men make up the typical FHCC patient population. Last, as inherent to all studies that use objective measures, there was the potential for laboratory magnesium level reporting errors.
Conclusion
The study results identified an association of PPI use and hypomagnesemia in a VA patient population of older men. More studies need to be conducted with non-VA patient populations to further assess the incidence of PPI-associated hypomagnesemia.
