P roton pump inhibitors (PPIs) are a class of medications indicated for the treatment of gastric acid–related dis- eases such as gastroesophageal reflux dis- ease and peptic ulcer disease, as well as part of Helicobacter pylori eradication regimens and for the prevention and treat- ment of nonsteroidal antiinflammatory drug–induced gastric injury. PPIs act by inhibiting the proton pump or H + /K + adenosine triphosphatase found on gastric mucosal parietal cells, therefore prevent- ing both basal and stimulated gastric acid secretion. 1 PPIs on the market are omepra- zole, esomeprazole, pantoprazole, rabepra- zole, lansoprazole, and dexlansoprazole. 1,2 Because of their superior efficacy and con- sistency in gastric acid suppression com- pared to histamine H 2 antagonists, PPIs are widely used in many countries. 2,3 In the US, PPIs ranked as the third-largest selling drug class in 2009. 4 In Australia, The Annals of Pharmacotherapy ■ 2013 June, Volume 47 ■ 773 Proton Pump Inhibitor–Associated Hypomagnesemia: What Do FDA Data Tell Us? Chee Phun Luk, Richard Parsons, Ya Ping Lee, Jeffery David Hughes theannals.com Gastroenterology RESEARCH REPORTS Author information provided at end of text. © 1967-2013 Harvey Whitney Books Co. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means without prior written permission of Harvey Whitney Books Co. For reprints of any article appearing in The Annals, please contact 415sales@hwbooks.com BACKGROUND: Proton pump inhibitors (PPIs) are a class of medications indicated for the treatment of gastric acid–related diseases. Hypomagnesemia is a rare but serious adverse effect of PPIs. OBJECTIVE: To address the association between the use of different PPIs and hypomagnesemia by examining the frequency of occurrence of hypomag- nesemia among the reported adverse drug reactions from the Food and Drug Administration (FDA) Adverse Event Reporting System database. METHODS: We conducted a cross-sectional study of PPI-associated adverse effect cases reported to the FDA between November 1, 1997, and April 1, 2012. Logistic regression was used to examine the association of sex, age, and different PPIs with hypomagnesemia. χ 2 Analysis was conducted to investigate the association of PPI- associated hypomagnesemia with hypocalcemia and hypokalemia. RESULTS: Among 66,102 subjects identified as experiencing 1 or more adverse effects while taking a PPI, 1.0% (n = 693) were reported to have hypomagnesemia. The mean (SD) age of PPI users presenting with hypomagnesemia was 64.4 (12.9) years. Results from logistic regression indicated that, compared with esomeprazole, all other PPIs had a higher rate of hypomagnesemia, with pantoprazole having the highest rate (OR 4.3; 95% CI 3.3-5.7; p < 0.001). The risk of female subjects having hypomagnesemia (OR 0.83; 95% CI 0.71-0.97; p = 0.016) was significantly lower than that of males. Elderly subjects (age >65 years) were at increased risk of PPI- associated hypomagnesemia (OR 1.5; 95% CI 1.2-1.7; p < 0.001). χ 2 Analysis showed strong association between hypomagnesemia and both hypocalcemia (p < 0.001) and hypokalemia (p < 0.001). CONCLUSIONS: All PPIs were associated with hypomagnesemia, with esomep- razole having the lowest risk and pantoprazole having the highest risk. The risk of PPI-associated hypomagnesemia was higher in males and the elderly population. Hypocalcemia and hypokalemia commonly coexisted with PPI-associated hypo- magnesemia. Ann Pharmacother 2013;47:773-80. Published Online, 30 Apr 2013, theannals.com, doi: 10.1345/aph.1R556 by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from