Proton-pump inhibitors, sometimes called PPIs, are medications designed to treat a number of gastrointestinal conditions, including frequent heartburn or more serious conditions like Zollinger-Ellison syndrome. PPI drugs work by blocking enzymes in the stomach that produce too much acid, alleviating symptoms for many health issues.
This class of drugs is among the most widely prescribed and used in the world, as they are considered the most effective inhibitors available and there are also many over-the-counter options available today. Millions of Americans purchase PPIs like Nexium, Prilosec and Prevacid every year. But within the last several years, many studies have emerged detailing potential health risks of using these medications long-term, leading to the U.S. Food and Drug Administration (FDA) releasing various additional warnings for proton-pump inhibitor treatments and thousands of consumers filing lawsuits against the drugs’ manufacturers.
What is a Proton-Pump Inhibitor?
Proton-pump inhibitors are a class of drugs meant to reduce stomach acid production. The stomach naturally produces acid to aid digestion and help kill bacteria, but some people experience issues from too much acid being produced and breaking down the protective linings in the stomach. This can lead to health issues like peptic ulcers, conditions in the esophagus and heartburn.
PPIs help block the stomach from over-producing acid by interfering with the body’s chemical system called the hydrogen-potassium adenosine triphosphatase enzyme system. The drug blocks the system’s H+/K+ ATPase enzyme, also known as a proton pump, which is responsible for gastric acid production. In blocking the enzyme, the stomach will produce less acid overall. Because of this, proton-pump inhibitors can treat and possibly prevent an array of gastrointestinal issues.
PPIs first came to the market in 1989 when the FDA approved Prilosec from manufacturer AstraZeneca. The drug was available only be prescription, but was later released in an over-the-counter version in 2003 with a slightly different formula. Now, there are many types of proton-pump inhibitors on the market that can be prescribed or bought directly by the consumer.
Available Proton-Pump Inhibitors
|Generic Name||Brand Names||Over-the-Counter Option|
|Omeprazole||Prilosec, Zegerid||Prilosec OTC, Zegerid OTC|
What Do Proton-Pump Inhibitors Treat?
Proton-pump inhibitors can treat a number of conditions, especially in their prescription forms. The dosage and how the medication is taken will depend on the condition being treated and if the drug was prescribed or bought directly from a drug store. With the more common over-the-counter forms, like Prilosec OTC or Nexium 24HR, consumers are supposed to take the medicine once daily over a two-week period. If heartburn or other symptoms persist, the treatment can be repeated once every four months depending on the health issue.
Conditions Treated by Proton-Pump Inhibitors
- Frequent heartburn
- Acid reflux
- Gastroesophageal reflux disease (GERD)
- Erosive esophagitis
- Barrett’s esophagus
- Duodenal and stomach ulcers
- Zollinger-Ellison syndrome (can be long-term treatment)
- Helicobacter pylori or h. pylori (combination treatment)
While there are a variety of PPIs available on the market, including many over-the-counter versions, there is no clear evidence that one agent is better than the other, like Prilosec OTC vs Nexium 24HR in treating acid reflux. However, studies have found that many of these drugs can cause serious side effects and adverse events, especially with long-term PPI use.
Proton-Pump Inhibitors Side Effects
When drugs like Prilosec and Nexium first came onto the market, the drug manufacturers only listed an array of mild PPI side effects like nausea, vomiting, diarrhea, stomach pain, headaches, dizziness, allergic reactions, and possible drug interactions for consumers on other medications. But as these drugs continued to grow in popularity, consumers began to experience more severe PPI side effects, like chronic kidney damage.
The FDA also released various warnings along with these studies, which has led to some label changes for drugs like Prevacid and Prilosec. Even with these studies and warnings, PPIs still account for billions of dollars in sales each year and remain widely prescribed and used around the globe.
2010: A study finds the potential increased risk of bone fractures, especially in the spine, hip and wrist in long-term use of PPI drugs. The FDA concluded an additional warning wasn’t necessary at the time because the fracture risk was low for short-term, low dose use.
2011: Researchers find prolonged use of prescription Prilosec, Nexium or Prevacid can cause low serum magnesium levels (hypomagnesemia), which can lead to muscle spasms, irregular heartbeat (arrhythmias), and seizures. The FDA required this warning to be added to the medications’ labels.
2012: The FDA warns about increased risk for clostridium difficile associated diarrhea (CDAD) when taking proton-pump inhibitors. Clostridium difficile (C. diff) is a bacteria that can cause diarrhea that will not improve, as well as abdominal pain, fever and even more serious intestinal conditions. These studies also caused the FDA to research the potential for CDAD from other similar drugs, like histamine blockers (h2 blockers) and antacids.
2013: In addition to the risk of hypomagnesemia, researchers published a study linking PPIs to an increased risk for vitamin and mineral deficiency, particularly vitamin C, vitamin B12, calcium and iron. These risks can be especially worrisome in seniors, as worsening vitamin deficiency can lead to other serious health issues.
2015: More studies emerged finding PPI users at a higher risk of stroke and heart attack. Health care professionals found a 21% increase in both strokes and heart attacks compared to non-users, which could be even higher in those needing a high dose for their condition.
2016: A study in JAMA Internal Medicine observed over 11,000 PPI users, and found that these consumers were 20 – 50% more likely to develop chronic kidney damage than the average person. Chronic kidney disease can progress to the point that patients require a kidney transplant to survive. Other similar studies also observed the serious side effects these drugs can have on the kidneys, including acute kidney injury, acute interstitial nephritis (AIN) and chronic kidney disease.
2017: Another study linked PPIs to the risk of sudden, early death. Researchers found that consumers taking PPIs over the course of one or two years were 50% more likely to die within the next 5 years than those taking similar h2 blockers, since PPIs can cause gradual, severe kidney disease.
There have been even more studies emerging backing up many of the warnings found since 2010, finding other possible injuries (like gastric cancer and higher risk of dementia) and further highlighting the dangers of continued proton-pump inhibitor use. Researchers say part of the problem is the freedom that comes with the over-the-counter options, since consumers can neglect to take the medication as directed. At the same time, many argue that the manufacturers didn’t properly test the drugs in the first place.
Proton-Pump Inhibitors Lawsuits
Because of these severe side effects, over 4,200 lawsuits have been filed against AstraZeneca’s Nexium and Prilosec, Takeda’s Prevacid, and other PPI manufacturers. The lawsuits allege that the manufacturers did not thoroughly test the effectiveness and safety of their products or properly warn doctors and consumers. Plaintiffs also state that the manufacturers falsely advertised the drugs to boost sales.
The majority of these lawsuits are under one MDL for various proton-pump inhibitors, MDL 2789. When the cases were first transferred to the MDL in August 2017, there were only 161 claims. The number of lawsuits filed has grown significantly within the last few months, and experts expect the trend to continue. These lawsuits are still in the early phases, and claimants are waiting for bellwether trials to be chosen for the proceedings to begin.