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Proton pump inhibitors and hospitalization with hypomagnesemia: a population-based case-control study

Zipursky J, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Paterson JM, Lathia N, Juurlink DN. PLoS Med. 2014; 11(9):e1001736. Epub 2014 Sep 30.

Background — Some evidence suggests that proton pump inhibitors (PPIs) are an under-appreciated risk factor for hypomagnesemia. Whether hospitalization with hypomagnesemia is associated with use of PPIs is unknown.

Methods and Findings — The researchers conducted a population based case-control study of multiple healthcare databases in Ontario, Canada, from April 2002 to March 2012. Cases were Ontarians aged 66 years or older hospitalized with hypomagnesemia. For each case, the researchers identified up to 4 controls matched on age, sex, kidney disease and use of various diuretic classes. Exposure to proton pump inhibitors was categorized according to the most proximate prescription prior to index date as current (within 90 days), recent (within 91 to 180 days) or remote (within 181 to 365 days). The researchers used conditional logistic regression to estimate the odds ratio for the association of outpatient proton pump inhibitor use and hospitalization with hypomagnesemia. To test the specificity of our findings we examined use of histamine H2 receptor antagonists, drugs with no causal link to hypomagnesemia. The researchers studied 366 patients hospitalized with hypomagnesemia and 1464 matched controls. Current proton pump inhibitor use was associated with a 43% increased risk of hypomagnesemia (adjusted odds ratio, 1.43; 95% CI 1.06 to 1.93). In a stratified analysis, the risk was particularly increased among patients receiving diuretics, (adjusted odds ratio, 1.73; 95% CI 1.11 to 2.70) and not significant among patients not receiving diuretics (adjusted odds ratio, 1.25; 95% CI 0.81 to 1.91). The researchers estimate that one excess hospitalization with hypomagnesemia will occur among 76,591 outpatient treated with a PPI for 90 days. In addition there was no association between hospitalization with hypomagnesemia and the use of histamine H2 receptor antagonists (adjusted odds ratio 1.06; 95% CI 0.54 to 2.06). Limitations of this study include a lack of access to serum magnesium levels, uncertainty regarding diagnostic coding of hypomagnesemia, and generalizability of our findings to younger patients.

Conclusions — PPIs are associated with a small increased risk of hospitalization with hypomagnesemia among patients also receiving diuretics. Physicians should be aware of this association, particularly for patients with hypomagnesemia. Please see later in the article for the Editors' Summary.

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Keywords: Drug interactions Gastrointestinal disorders