Reports have linked long-term use of proton pump inhibitors with hypomagnesemia, and discontinuation of the drug might be necessary for resolution of symptoms, the Food and Drug Administration announced on March 2.
"Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic," according to the FDA statement posted on the agency’s MedWatch site. In the statement, the agency recommended that health care professionals "should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics, or drugs that may cause hypomagnesemia." They should also consider periodically checking magnesium levels in these patients, the statement adds.
The alert was prompted by a review of 38 cases of hypomagnesemia in patients on prolonged PPI therapy reported to the FDA’s Adverse Event Reporting System and 23 cases reported in the medical literature (which included at least 8 of the AERS reports), which "suggests there is an association between serious adverse events related to hypomagnesemia and prolonged PPI use," the FDA said.
Some cases of hypomagnesemia have been reported in adults taking PPIs for at least 3 months, but most cases have been reported in people who have taken the PPI for more than a year. In some cases, treatment with magnesium supplements was not adequate and the patient has to stop taking the PPI to achieve resolution of symptoms, according to the FDA.
While the mechanism for hypomagnesemia is not known, long-term use of PPIs may affect intestinal absorption of magnesium, the statement said.
If over-the-counter PPIs are used as labeled, at low doses and only for 14 days of treatment up to three times a year, "FDA believes that there is very little risk of hypomagnesemia," the statement said.
Currently available prescription PPIs include esomeprazole magnesium (Nexium), dexlansoprazole (Dexilant), omeprazole (Prilosec), omeprazole and sodium bicarbonate (Zegerid), lansoprazole (Prevacid), pantoprazole sodium (Protonix), and rabeprazole sodium (AcipHex).
In 2009, about 21 million prescriptions for PPIs were filled at outpatient retail pharmacies in the United States, and people who take prescription PPIs usually continue treatment for an average of about 180 days, according to the FDA.
Serious adverse events associated with the use of PPIs and other drugs should be reported at the MedWatch Web site or by phoning 800-332-1088.