Comparison of Continuous Infusion vs Intermittent (BID) Proton Pump Inhibitor Therapy (Esomeprazole) in Upper Gastrointestinal Hemorrhage (Eur J Intern Med, 2011) [MEDLINE]: n = 132
Continuous Infusion was Not Superior to Intermittent (BID) Proton Pump Inhibitor Dosing in Terms of Re-Bleeding, Need for Surgery, or Mortality Rate in Upper Gastrointestinal Hemorrhage
Meta-Analysis of Gastric Acid Suppression (Am J Gastroenterol, 2012) [MEDLINE]
Probable Association Between PPI Use and Clostridium Difficile Infection: risk is further increased by concomitant use of antibiotics and Proton Pump Inhibitors
H2-Blockers May Carry Lesser Risk of Clostridium Difficile Infection
United States Food and Drug Administration 2012 Review of Published Literature and Drug Safety Communication Regarding the Risk of Gastric Acid Suppression on the Incidence of Clostridium Difficile Infection [LINK]
Most Studies Suggest an Increased 1.4-2.75x-Increased Risk of Clostridium Difficile Infection with PPI Use, as Compared to Patients without Proton Pump Inhibitor Use
Meta-Analysis Studying the Association Between Proton Pump Inhibitor and Clostridium Difficile Infection (Clinical Gastroenterology and Hepatology, 2012) [MEDLINE]
Proton Pump Inhibitor Use was Associated with a 2x-Increased Risk of Clostridium Difficile Infection
Retrospective Case-Control Study Studying PPI Use and Clostridium Difficile Infection (Mayo Clin Proc, 2013) [MEDLINE]
Duration of Proton Pump Inhibitor Use was Significantly Associated with Clostridium Difficile Infection
Retrospective Cohort Analysis Studying Proton Pump Inhibitor Use and Recurrent Clostridium Difficile Infection in Hospitalized Patients (Am J Gastroenterol, 2013) [MEDLINE]
Among Hospitalized Patients with Clostridium Difficile Infection, Receipt of Proton Pump Inhibitors Concurrent with Clostridium Difficile Treatment was Not Associated with Recurrence of Clostridium Difficile Infection
Recurrence of Clostridium Difficile Infection was Significantly Associated with Black Race, Increased Age, and Increased Comorbid Disease
Hypomagnesemia Has Been Reported with the Chronic Use of Omeprazole and Other Proton Pump Inhibitors (see Omeprazole)
FDA Has Issued a Safety Warning in 2011 Regarding this Risk
Measurement of Magnesium is Recommended During Prolonged Therapy
Risk of Hypomagnesemia is Increased by the Concomitant Use of Diuretics
Physiology
Hypomagnesemia is a Class Effect
Inhibition of Transient Receptor Potential Melastatin-6 (TRPM6) and Transient Receptor Potential Melastatin-7 (TRPM7) Channels, Resulting in Impaired Intestinal Epithelial Cell Absorption of Magnesium
Clinical
Hypocalcemia (see Hypocalcemia): may also be present
Low Parathyroid Hormone (see Hypoparathyroidism): may be seen in some cases (note: inappropriately low parathyroid hormone may be seen in other causes of hypomagnesemia, as well)
Treatment
Hypomagnesemia Resolves with Cessation of the Proton Pump Inhibitor Therapy
References
General
Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapy. Br J Clin Pharmacol. 2009;67:44-49 [MEDLINE]
Delayed elimination of methotrexate associated with co-administration of proton pump inhibitors. Anticancer Res. 2010;30:3807-3810 [MEDLINE]
Comparison of infusion or low-dose proton pump inhibitor treatments in upper gastrointestinal system bleeding. Eur J Intern Med. 2011 Apr;22(2):200-4. doi: 10.1016/j.ejim.2010.11.007 [MEDLINE]
Accumulating evidence for a drug-drug interaction between methotrexate and proton pump inhibitors. The Oncologist. 2012;17:550-555 [MEDLINE]
Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma. Leuk Lymphoma. 2012;53:1867-1875 [MEDLINE]
2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23;64(24):e139-228. doi: 10.1016/j.jacc.2014.09.017. Epub 2014 Sep 23 [MEDLINE]
Adverse Effects
Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. N Engl J Med. 2006;355(17):1834 [MEDLINE]
Severe hypomagnesaemia in long-term users of proton-pump inhibitors. Clin Endocrinol (Oxf). 2008;69(2):338 [MEDLINE]
Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med. 2009;151(10):755 [MEDLINE]
Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Archives of Internal Medicine 2010; 170 (9): 784–90. doi:10.1001/archinternmed.2010.89 [MEDLINE]
Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107(7):1011 [MEDLINE]
United States Food and Drug Administration 2012 Review of Published Literature and Drug Safety Communication Regarding the Risk of Gastric Acid Suppression on the Incidence of Clostridium Difficile Infection [LINK]
Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clinical Gastroenterology and Hepatology 2012; 10 (3): 225–33 [MEDLINE]
Proton Pump Inhibitors and the Risk for Hospital-Acquired Clostridium difficile Infection. Mayo Clin Proc. 2013 Oct;88(10):1085-1090. Epub 2013 Sep 5 [MEDLINE]
Proton pump inhibitors and risk for recurrent Clostridium difficile infection among inpatients. Am J Gastroenterol. 2013 Nov;108(11):1794-801. Epub 2013 Sep 24 [MEDLINE]
