The U.S. Food and Drug Administration (FDA) warns that prescription proton pump inhibitor (PPI) drugs may cause low serum magnesium levels (hypomagnesemia) if taken for prolonged periods of time, in most cases, longer than one year.

In approximately one-quarter of the cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued.

PPIs work by reducing the amount of acid in the stomach and are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus. In 2009, approximately 21 million patients filled PPI prescriptions at outpatient retail pharmacies in the United States. Patients who take prescription PPIs usually stay on therapy for an average of about 180 days (6 months).

Prescription PPIs include Nexium (esomeprazole magnesium), Dexilant (dexlansoprazole), Prilosec (omeprazole), Zegerid (omeprazole and sodium bicarbonate), Prevacid (lansoprazole), Protonix (pantoprazole sodium), and AcipHex (rabeprazole sodium). Vimovo is a prescription combination drug product that contains a PPI (esomeprazole magnesium and naproxen).

Over-the-counter (OTC) PPIs include Prilosec OTC (omeprazole), Zegerid OTC (omeprazole and sodium bicarbonate), and Prevacid 24HR (lansoprazole).

In contrast to prescription PPIs, OTC PPIs are marketed at low doses and are only intended for a 14 day course of treatment up to 3 times per year. FDA believes that there is very little risk of hypomagnesemia when OTC PPIs are used according to the directions on the OTC label.