Gastroesophageal reflux disease is one of the most commonly treated diseases. It is sometimes referred to as heartburn, although this is more of a symptom. In line with this, proton pump inhibitors (PPIs) have become one of the top-10 drug classes prescribed or taken in the United States.
The class of drugs called PPIs includes Prevacid (lansoprazole), Prilosec (omeprazole), Nexium (esomeprazole), Protonix (pantoprazole) and Aciphex (rabeprazole). Several of these medications are now available over-the-counter (OTC), rather than by prescription.
When they were first approved, they were touted as having one of the cleanest side-effect profiles. This may still be true, if we use them correctly. They are intended to be used only for the short term. This can range from 7 to 14 days for over-the-counter PPIs to 4 to 8 weeks for prescription PPIs.
Long-term use dangers
While PPI pre-approval trials were short-term, not longer than a year, many physicians put patients on these medications for decades. And the longer people are on them, the more complications arise. Among potential associations with long-term use are chronic kidney disease, dementia, bone fractures and Clostridium difficile, a bacterial infection of the gastrointestinal tract.
Chronic kidney disease
In two separate studies, results showed that there was an increase in chronic kidney disease with prolonged PPI use. All of the patients started the study with normal kidney function.
In the Atherosclerosis Risk in Communities (ARIC) study, there was a 50 percent increased risk of chronic kidney disease, while the Geisinger Health System cohort study found there was a 17 percent increased risk.
The first study had a 13-year duration, and the second had about a six-year duration. Both demonstrated modest, but statistically significant, increased risk of chronic kidney disease.
As you can see, the medications were used on a chronic basis for years. In an accompanying editorial to these published studies, the author suggests starting with diet and lifestyle modifications as well as a milder drug class, H2 blockers.
Bone fractures
In a meta-analysis of 18 observational studies, results showed that PPIs can increase the risk of hip fractures, spine fractures and any-site fractures. It did not make a difference whether patients were taking PPIs for more or less than a year.
They found increased fracture risks of 58, 26 and 33 percent for spine, hip and any site, respectively. It is not clear what may potentially increase the risk; however, it has been proposed that it may have to do with calcium absorption.
PPIs reduce acid, which may be needed to absorb insoluble calcium salts. In another study, seven days of PPIs were shown to lower the absorption of calcium carbonate supplements when taken without food.
Magnesium absorption
PPIs may have lower absorption effects on several electrolytes including magnesium, calcium and B12. In one observational study, PPIs combined with diuretics caused a 73 percent increased risk of hospitalization due to low magnesium.
A significant reduction in magnesium could lead to cardiovascular events. Diuretics are commonly prescribed for high blood pressure, heart failure and swelling.
The bottom line is that it’s best if you confer with your doctor before starting PPIs. You may not need PPIs, but rather a milder medication, such as H2 blockers (Zantac, Pepcid).
Even better, start with lifestyle modifications including diet, not eating later at night, raising the head of the bed, losing weight and stopping smoking, if needed, and then consider medications.
If you do need medications, know that PPIs don’t give immediate relief and should only be taken for a short duration: 7 to 14 days, according to the FDA, without a doctor’s consult, and 4 to 8 weeks with one.
