Long-term use of prescription proton pump inhibitors, or PPIs, can depress serum magnesium levels and, possibly, lead to serious adverse events, the FDA announced recently. Such adverse events can include tetany, arrhythmias and seizures.
According to the agency, about 21 million patients filled prescriptions for PPIs at U.S. retail pharmacies in 2009. Patients stayed on the medications -- which reduce the amount of acid in the stomach and are used to treat such conditions as gastroesophageal reflux disease, stomach and small intestine ulcers, and esophagitis -- for an average of 180 days.
In a March 2 safety announcement(www.fda.gov), the FDA said prolonged use -- longer than one year -- of the medications was associated with adverse events.
Eight prescription PPIs were included in the FDA's safety announcement:
- esomeprazole magnesium, which is marketed as Nexium;
- dexlansoprazole, which is marketed as Dexilant;
- omeprazole, which is marketed as Prilosec;
- omeprazole and sodium bicarbonate, which is marketed as Zegerid;
- lansoprazole, which is marketed as Prevacid;
- pantoprazole sodium, which is marketed as Protonix;
- rabeprazole sodium, which is marketed as AcipHex; and
- the combination drug naproxen and esomeprazole magnesium, which is marketed for arthritis relief as Vimovo.
The FDA alerted physicians and consumers on March 2 that prescription proton pump inhibitors, or PPIs, may cause hypomagnesemia if taken for prolonged periods. However, the agency said there is little risk of low serum magnesium levels when OTC PPIs are used appropriately. OTC versions of the drugs are marketed at low doses and are intended for a 14-day course of treatment as many as three times per year.
Available OTC versions of PPIs include:
- omeprazole, which is marketed as Prilosec OTC;
- omeprazole and sodium bicarbonate, which is marketed as Zegerid OTC; and
- lansoprazole, which is marketed as Prevacid 24HR.
Physicians writing prescriptions for PPIs first should consider obtaining serum magnesium levels, the agency advised. In addition, levels should be checked periodically after beginning PPI therapy in a patient who is expected to need prolonged treatment or who also is taking a medication that causes hypomagnesemia, such as a loop or thiazide diuretic.
The FDA said checking serum magnesium levels was particularly important in patients taking the heart medication digoxin because low magnesium can increase the likelihood of serious side effects associated with that drug.
Magnesium supplements can be used to treat hypomagnesemia. However, patients who develop the condition may need to discontinue PPI therapy in addition to supplementing their magnesium levels. In one-fourth of the cases reviewed by the FDA, supplementation alone did not improve low serum magnesium levels.
The agency issued the following information for physicians:
- Advise patients to seek immediate medical care if they experience signs of hypomagnesemia, including arrhythmias, tetany, tremors or seizures, while taking PPIs. In children, arrhythmias may cause fatigue, upset stomach, dizziness and lightheadedness.
- Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic.
- OTC versions of the drugs are marketed at lower doses and are intended for a 14-day course of treatment as many as three times per year. However, physicians should be aware that consumers may take OTC PPIs for periods of time that exceed directions on OTC labels. Physicians who recommend prolonged use of an OTC product should tell patients about the risk of hypomagnesemia.
- Report adverse events involving PPIs to the FDA's MedWatch program(www.accessdata.fda.gov).