If you're like millions of Americans, it's possible you're taking a popular class of acid-reducing drugs called proton-pump inhibitors that are prescribed and available over the counter to combat issues ranging from heartburn and acid reflux to gastroesophageal reflux disease, or GERD.
PPIs, which include heartburn drugs such as Prilosec, Nexium and Prevacid, are one of the best-selling classes of drugs in the world. "They're extremely effective and widely considered safe. They treat a variety of upper intestinal issues, and they've actually revolutionized the treatment of those conditions – specifically acid reflux, gastritis, gastric ulcers and duodenal ulcers," says Dr. Leo Treyzon, clinical chief in the division of gastroenterology at Cedars-Sinai Medical Center in Los Angeles. "We had good medicines before in the form of Zantac or other H2-blockers, but these are far more effective, and their side effect profile was very good. Only until recently did we see that there was an expanded side effect profile."
Despite their effectiveness, PPIs have faced increasing scrutiny as research has found the drugs to be associated with risks ranging from vitamin deficiencies to kidney damage and chronic kidney disease, as well as dementia. Experts say patients are routinely left on the drugs – which are approved by the Food and Drug Administration for short-term use – indefinitely, and often even after they're no longer needed or don't provide therapeutic benefit.
Risks Associated With PPIs
Taking PPIs has been linked to an increased risk of pneumonia and a higher risk of developing a digestive system infection called clostridium difficile that causes diarrhea and can be life-threatening. In addition, PPIs can affect absorption of vitamins and minerals and have been found to be associated with certain deficiencies, such as for vitamin B12, calcium, iron and magnesium, says Dr. Joel Heidelbaugh, a clinical professor of family medicine at the University of Michigan—Ann Arbor, who has done research on the overutilization of PPIs and risks associated with this class of drugs. He notes there's now also concern PPIs could possibly affect kidney function and be linked to a higher risk of developing chronic kidney disease. "Of course, all of these associations were determined retrospectively," he says. The drugs haven't been studied prospectively to prove a cause-and-effect relationship between taking PPIs and the health issues studied. But experts say the risks are worth considering when deciding whether to start or continue on PPIs.
Most recently, a study published online in April in the Journal of the American Society of Nephrology found patients who take PPIs for heartburn, acid reflux or ulcers were more likely to experience a decline in kidney function, compared to those taking H2 blockers, and had an increased risk of developing chronic kidney disease and kidney failure. Researchers found the longer patients took PPIs, the greater an individual's risk. Regarding possible vitamin deficiencies associated with PPIs, Heidelbaugh notes in recent years that attention has turned toward magnesium. Low levels of magnesium have been linked to issues ranging from osteoporosis to high blood pressure. In addition, research published last year in the online open-access journal PLOS One found that taking PPIs was associated with an increased risk of heart attack.
The findings have led some physicians and patients to proceed with added caution and brought concerns about overutilization of PPIs into sharper focus. "I think having the medication over the counter drives some overuse," Heidelbaugh says. He believes it's likely many people follow drug package directions, however, and use PPIs for the recommended period of time, which is generally two weeks. "But I think many times doctors put patients on these medications without a clear indication or without a clear plan for follow-up, and then they're left on the medications."
Experts stress that patients should work with their physicians – and consider seeing a gastroenterologist, a doctor who specializes in diagnosing and treating diseases of the digestive system – to ensure they have a correct diagnosis and regularly reassess and discuss if they need to continue taking PPIs. A person taking PPIs over the counter should also keep his or her doctor in the loop, particularly if considering taking the drugs for a longer duration than recommended, and to discuss alternatives and lifestyle changes that may help.
Heidelbaugh notes that frequently it's necessary and appropriate for patients to continue taking PPIs indefinitely. "There's a lot of people who will need it, and there's a lot of people who will need it long term." But there are others who are put on the medications, such as for not well-defined stomach pains or a variety of upper gastrointestinal symptoms that don't warrant being prescribed an acid-reducing medication in the first place, he says.
Drugs Used in Diagnosising Patients, Too
To better understand a patient's health concern, PPIs are used not only as treatment but – in the short term – as a diagnostic test to investigate specific issues like acid reflux, Treyzon explains. That's done rather than initially performing an endoscopy, a nonsurgical procedure to look inside a person's digestive tract. "Before we look, now we treat," he says. "But if people have a fear of going on these medicines, then that might change, and maybe someone's first strategic step is to do an endoscopy before trying a medicine. And a lot of people do because they're already scared of medicines. But for some people, they had comfort in knowing that doctors recommended a treatment trial first as a diagnostic test and as a treatment."
In discussing newly discovered risks associated with PPIs, Treyzon says he's finding patients are more eager to determine whether they might instead take an H2-blocker, drugs that reduce the amount of acid secreted by cells in the lining of the stomach, even if that class of medication didn't work for them before. Though Treyzon still finds PPIs to be more effective, he says PPIs and H2-blockers are both safe, acid-reducing treatment options. "Proton-pump inhibitors, when taken for a long time, might have some extra risks, like low magnesium levels or risk of osteoporosis. These things are measurable, preventable and treatable," he says. But, he adds, when talk turns to nontreatable issues like dementia – however rare the associated risk might be – that changes the discussion.
Even if patients are given pause, experts say their options may be limited. For the most part, those Treyzon sees who take PPIs need to stay on medication for the longer term, he says, because they're dealing with long-term conditions. However, in addition to some patients who opt for more invasive treatment like surgery, some others may also be able to discontinue taking medicines. In such cases, "we often recommend [stopping the drugs] cold turkey," Treyzon says. He says so-called rebound hyperacidity – where the body produces more acid, and a person is left to deal with increasing sickness and symptoms as a result of coming off acid-reducing drugs – is not common. Though he will taper doses for a patient who's concerned about discomfort from returning symptoms, he says it's not necessary to do so with PPIs as it is with some other drugs.
Lifestyle modifications may also help address issues such as heartburn or acid reflux. "Stopping smoking; not eating late at night; not reclining immediately after you eat; eating smaller meals as opposed to larger meals," determining one's particular food triggers, since not everyone's the same; and losing weight are all recommended steps one can take, Treyzon says. However, despite such efforts, he adds, patients typically continue to get sick and have symptoms if they don't take medicine. Still, even in such cases where patients need to stay on the medication, experts say that it's worth checking with the doctor to see if it's appropriate to reduce the dose and/or take PPIs less frequently.
Cardiologist Dr. Nicholas Leeper, chief of vascular medicine at Stanford University in Stanford, California, and senior author of research published in PLOS One that found PPI use was associated with a higher heart attack risk, doesn't recommend patients discontinue PPIs as a result of those findings. But he urges taking a prudent approach, particularly for those taking the drugs over the longer term. "These are a highly effective and well-studied class of drugs that are typically well-tolerated," Leeper says. "But I would say that this study shows you that all medicines have some risks, and I think it just reinforces the need to carefully weigh the risks and benefits of any drug."
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