Proton Pump Inhibitors (PPIs)

Proton pump inhibitors (PPIs) are common medications best known by their brand names, including Nexium, Prevacid and Prilosec. They decrease acid secretion in your stomach and relieve conditions like gastroesophageal reflux disease (GERD), indigestion, ulcers and more.

Research indicates a potential link between the use of PPIs and medical issues, including kidney disease and cognitive decline.

Many people who developed these conditions after using PPIs filed lawsuits claiming that manufacturers failed to warn them about possible side effects. Some cases were settled, while others are pending. If you’ve been injured by PPI use, you can still file a claim.

Proton pump inhibitors (PPIs) are drugs that lower acid production in your stomach. This acid helps you digest food and kills dangerous germs. However, if your body produces too much acid or it ends up in the wrong place, you may experience issues like acid reflux or ulcers.

Some PPIs are available over the counter or with a prescription, including:

• Esomeprazole (Nexium)
• Lansoprazole (Prevacid)
• Omeprazole (Prilosec)
• Omeprazole/sodium bicarbonate (Zegerid)

Other PPIs require a prescription, including:

• Dexlansoprazole (Dexilant)
• Pantoprazole (Protonix)
• Rabeprazole (AcipHex)

Over-the-counter PPIs are generally used for short durations at lower doses. Prescription PPIs are used for more severe conditions and taken at higher doses for longer treatment periods.

How Do PPIs Work?

PPIs block an enzyme that makes stomach acid, the hydrogen-potassium ATPase pump. It’s also known as your “proton pump.” PPIs keep your body’s proton pump from completing the chemical reactions that produce stomach acid.

These medications don’t completely stop your body from creating acid, but they reduce production. According to the Cleveland Clinic, PPIs cause a roughly 65% reduction in stomach acid, leaving you with 35% to help you digest food.

PPIs are an alternative to other medications that reduce stomach acid, like H2 blockers and antacids. H2 blockers create a histamine receptor blockade to lower stomach acid production. Antacids block pepsin, a proteolytic enzyme that aids in digestion, and neutralize acid using ingredients like aluminum, calcium and magnesium.

What Conditions Do PPIs Treat?

PPIs can help treat gastroesophageal reflux disease, ulcers, H. pylori infections and Zollinger-Ellison syndrome.

It can take around 24 hours for PPIs to work effectively. Consider consulting with your health care provider before taking these medications to determine the proper dosage and how long you should take them.

Most short-term side effects of proton pump inhibitors are gastrointestinal. Patients report symptoms such as nausea, diarrhea, flatulence and constipation. Some patients may also experience headaches and dizziness.

Furthermore, the prescribing information for a popular PPI medication, Prilosec, warns of a potential interaction with clopidogrel, a heart disease medication. This interaction may diminish the efficacy of clopidogrel.

“As a pharmacist, I’ve seen many patients struggle with side effects from short-term PPI use,” Sazan Sylejmani, pharmacy manager at Westmont Pharmacy in Westmont, Ill., told Drugwatch. “My advice is to take the lowest effective dose for the shortest time necessary.”

A 2021 study published in the British Journal of Clinical Pharmacology showed that PPIs have a mild connection to an increased short-term risk of death from cardiovascular complications such as heart disease. A review in BMC Medicine from the same year also showed a 16% increased risk of stroke associated with regular PPI use.

Additionally, a 2020 study in the Annals of Gastroenterology highlights the increased risk of pneumonia with PPI use.

While there were initial concerns about a connection between PPIs and Alzheimer’s disease, a 2022 review in the British Journal of Pharmacology showed “no clear evidence for an association between PPI intake and the risk of dementia.”

Severe Side Effects of PPIs

Severe side effects of proton pump inhibitors include an increased risk of Clostridium difficile-associated diarrhea, bone fracture, stomach cancer, kidney injury and stroke.

The FDA requires that PPI labels contain several additional warnings for potentially serious side effects. These side effects are uncommon, but patients should still be aware of them.

These issues can appear after a single use of PPIs but are more likely to develop after prolonged treatment. Talk to your doctor before beginning a course of PPIs if you are concerned about any vitamin deficiencies, bone fractures or kidney problems.

Gastric and Esophageal Cancer

Recent research points to a correlation between PPI usage and gastric cancer. In 2023, Frontiers in Pharmacology published a meta-analysis of 24 studies that found a significant increase in gastric cancer, also known as stomach cancer, diagnoses among patients taking PPIs. Patients who used PPIs long-term were especially at risk.

Researchers have also linked proton pump inhibitors to esophageal cancer. A 2022 case-control study published in Pharmaceuticals looked at data from over 4,000 patients in South Korea. It showed higher rates of esophageal cancer among participants who had previously taken PPIs or H2-receptor antagonists.

A Swedish study published in Cancer Epidemiology in 2021 evaluated participants for their risk of gastric and esophageal cancer while on PPIs and after discontinuing the drug.

The research team found that PPI users were 7-10 times more likely than non-users to develop gastric and esophageal cancer during their first year of taking PPIs. The risk remained elevated for all patients after the first year, ranging from a 24% to 202% increased risk compared to the general population.

Kidney Injury and Disease

A significant body of research demonstrates a relationship between PPI usage and “silent” kidney damage.

The Journal of Clinical Medicine published a 2023 analysis of 10 observational studies looking at 6.8 million people with a range of comorbidities. The results overwhelmingly supported the claim that PPIs taken for an extensive period can cause kidney issues. The study authors recommend continuous monitoring of at-risk patients to help ensure early detection in case of kidney dysfunction.

This builds upon earlier analysis of the FDA adverse event reporting system reported in 2021 in Scientific Reports. The analysis found that kidney disease most commonly occurred within the first year of use. Earlier studies found a correlation between PPI use and chronic kidney disease and kidney failure, also known as end-stage renal disease.

Other Notable PPI Safety Studies

A 2018 study published in Therapeutic Advances in Drug Safety revealed that PPI use was associated with an increased risk of dying from any cause. However, the study did not offer a clear explanation as to why this was the case.

Researchers from a study published in the Journal of Infection found a potentially increased risk of Clostridioides difficile infection based on how long someone uses PPI and their dosage.

According to a study in Mayo Clinical Proceedings, PPI users might be at twice the risk of developing heart failure or cardiovascular disease. Additionally, a study in Springer Nature found an asthma risk in children linked to PPI use by mothers while their baby was in utero.

The FDA has issued PPI warnings, including alerts about the dangers of decreased magnesium levels from long-term use and a higher risk of hip, wrist and spine fractures. A warning was also issued about the increased risk of gastrointestinal infections that can cause diarrhea.

Some PPI manufacturers have added alerts to their product’s packaging that match warnings from the FDA. For example, Nexium’s label lists some of the information included in the FDA advisories.

The FDA guidelines on PPI use are more relaxed than in many other countries. For example, in the United Kingdom, the National Institute for Clinical Excellence suggests more selective use of PPIs. It also advises reviewing their use at least annually when used long term.

Have Any PPIs Been Recalled?

Glenmark Pharmaceuticals Inc. USA recalled 30 and 100-count bottles of esomeprazole magnesium delayed-release capsules in 2023. An FDA Enforcement Report showed elevated results for organic impurities that exceeded allowable amounts.

Pfizer recalled more than 500,000 vials of their PPI Protonix because it may have been subpotent. The FDA eventually identified it as a class III recall. An FDA class III recall means that the capsule is not likely to cause harm.

Dr. Reddy’s Laboratory recalled two of their Lansoprazole products due to the drug’s therapeutic concentration potentially varying throughout the day.

Additionally, due to incorrect National Drug Code numbers, Zydus Pharmaceuticals recalled their Esomeprazole Magnesium for Delayed-Release Oral Suspension 40mg drug in 2024.

Thousands of lawsuits have been filed against PPI manufacturers. Many of these cases rely on studies that link proton pump inhibitors to serious medical conditions. In 2019, lawsuits against PPI manufacturers related to kidney issues were combined into one multidistrict litigation (MDL) in New Jersey.

MDLs may occur when lawsuits with similar allegations are filed against the same defendants. These cases go through most of the legal process together and are presented to one judge.

Plaintiffs in the PPI MDL allege that their use of proton pump inhibitors caused medical issues, including acute interstitial nephritis, chronic kidney disease and other types of kidney damage. They claim manufacturers failed to provide adequate warnings about the dangers of the drugs.

Lawsuits are ongoing, but some defendants have settled. AstraZeneca agreed to pay $425 million to resolve product liability litigations related to Nexium and Prilosec. Additional settlements were reached with GlaxoSmithKline, Procter & Gamble, Pfizer and Takeda Pharmaceuticals.

Lawsuits were also filed related to bone damage resulting from Nexium, which were consolidated into an MDL. While Takeda Pharmaceutical Company settled several claims for an undisclosed sum, a judicial ruling that the plaintiffs couldn’t prove causation ended the bone density MDL in January 2017.

There are 11,808 active PPI lawsuits still pending in the MDL. More plaintiffs may pursue claims seeking compensation for their losses.

Who Is Eligible to File a PPI Lawsuit?

Since the current MDL focuses on kidney damage claims, patients who used PPIs and sustained issues related to their kidneys might be eligible to file a proton pump inhibitor lawsuit.

You can consult an experienced attorney to determine if you can join the MDL or pursue a claim. Drugwatch can connect you to a lawyer for a free consultation.