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Proton pump inhibitor therapy is associated with hospitalization for hypomagnesemia


Patients prescribed proton pump inhibitors (PPIs) in combination with diuretics face increased risk of hospitalization for low blood magnesium, according to a new study by researchers at the Institute for Clinical Evaluative Sciences (ICES).

The study published today in PLOS Medicine suggests that physicians reconsider long-term PPI therapy for patients who experience significant hypomagnesemia.

“What we found was that current PPI users have a 43 per cent increased risk of hospitalization with hypomagnesemia over patients with no PPI prescription. The risk was particularly increased among patients receiving diuretics, which can also affect magnesium levels,” said Dr. David Juurlink, senior author and scientist at ICES.

Roughly 145 million prescriptions for PPIs are dispensed in the United States annually for acid-related disorders such as dyspepsia and gastroesophageal reflux, and these drugs are widely regarded as safe. However, several adverse effects of PPIs have been identified. Since 2006, 30 case studies have linked long-term use of PPIs to hypomagnesemia, which may reflect impaired intestinal absorption of magnesium. Hypomagnesemia is dangerous when severe; it can be associated with malignant cardiac arrhythmias, muscle weakness and seizures. Consequently, physicians require clear guidance for prescribing PPI in patients at risk for hypomagnesemia.

The researchers examined Ontario data from 2002 to 2012. They identified PPI prescription records from 366 patients (aged 66 and older) hospitalized with hypomagnesemia and 1464 matched controls. Based on these data, current PPI users have a 43 per cent increased risk of hypomagnesemia over patients with no PPI prescription in the past year. The risk was particularly increased among patients receiving diuretics, which may affect renal magnesium flux, and not significant among patients not receiving diuretics.

The authors estimate that this is a rare complication of PPI therapy, with one excess hospitalization for hypomagnesemia for every 76,591 outpatients who take a PPI for 3 months. While, as the authors note, the vast majority of PPI-users will not develop the condition, severe low magnesium may be “an underappreciated consequence of PPI use, particularly given the high background use of PPIs in the general population.”

ICES is an independent, non-profit organization that uses population-based health information to produce knowledge on a broad range of healthcare issues. Our unbiased evidence provides measures of health system performance, a clearer understanding of the shifting healthcare needs of Ontarians, and a stimulus for discussion of practical solutions to optimize scarce resources. ICES knowledge is highly regarded in Canada and abroad, and is widely used by government, hospitals, planners, and practitioners to make decisions about care delivery and to develop policy.

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