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Proton Pump Inhibitor (PPI) Side Effects

Proton pump inhibitor (PPI) side effects can include kidney damage, heart attacks and cancers. More common side effects of proton pump inhibitors are constipation, stomach pain, headache diarrhea and vomiting. Some side effects can occur at any time after starting PPI therapy. Proton pump inhibitors are potent heartburn medicines that reduce stomach acid. PPI drugs include Prilosec and Nexium. The drugs’ labels do not include all potential PPI side effects.

Suffering from serious side effects after taking a PPI?

If you took a Proton Pump Inhibitor (PPI) like Nexium or Prilosec and suffered kidney damage or injuries, you may be entitled to compensation.

Nexium, Prevacid & Dexilant
PPI Side Effects
  1. Kidney disease, injury & failure develops silently and gradually over time
  2. Acute interstitial nephritis (AIN) can lead to kidney failure
  3. Hip, wrist and spine fractures risk greatest for people taking PPIs long-term at high doses
  4. C. diff.-associated diarrhea linked to bacterial infections
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Studies have linked proton pump inhibitors to serious, sometimes life-threatening side effects. Higher dosages and long-term use increases the risk for many of those complications.

Side effects of long-term use of proton pump inhibitors can include kidney disease, kidney injury and kidney failure. Other possible PPI side effects include heart attacks, cancers and bone fractures.

Common side effects of proton pump inhibitors are constipation, diarrhea, headache, itching, nausea, stomach pain and vomiting. Side effects can occur any time after a person starts taking PPI drugs.

The U.S. Food and Drug Administration requires warnings in the drugs’ labels. The warnings include a serious PPI drug interaction. But not all potential PPI side effects are included.

Recent studies have associated long-term PPI use and chronic kidney disease (CKD). The FDA has not told manufacturers to add a CKD warning to PPI labels.

People who suffered kidney problems after taking PPIs are suing drugmakers. Proton pump inhibitor lawsuits say the manufacturers did not warn of the serious risk associated with long-term use of PPIs.

What Are the Side Effects of Long-Term Use of Proton Pump Inhibitors?

Studies show that side effects of long-term use of proto pump inhibitors can range from low vitamin B12 levels to gastric cancer or kidney failure. Patients should ask their doctor about proton pump inhibitor side effects with long-term use.

Potential Side Effects of Long-Term Use of Proton Pump Inhibitors Include
  • Kidney disease, injury & failure
  • Hip, wrist and spine fractures
  • Esophageal cancer
  • Gastric cancer
  • Pneumonia
  • Clostridium difficile (C. diff.) infections
  • Vitamin B12 deficiency
  • Low magnesium levels
  • Lupus erythematosus events
Certified health practitioner Rebecca Montrone discusses side effects of PPIs.

PPIs and Kidney Problems

Studies dating back to the 1990s have associated PPIs with kidney problems. Recent research underlined the kidney risk of PPIs.

Kidney Problems Linked to PPIs Include
  • Kidney disease
  • Kidney injury (acute interstitial nephritis)
  • Kidney failure

A 2017 study found PPI use could lead to “silent” kidney damage. Researchers looked at 125,000 PPI users over five years. They zeroed in on those who developed chronic kidney disease (CDK). Half the people who developed CDK had never experienced kidney problems before starting PPIs.

“Our results indicate kidney problems can develop silently and gradually over time, eroding kidney function and leading to long-term kidney damage or even renal failure.”

Source: Dr. Ziyad Al-Aly, study author and assistant professor of medicine at Washington University School of Medicine

A 2016 study looked at PPIs and kidney disease. It found long-term PPI users were 95 percent more likely to experience kidney failure. This is also called end-stage renal disease (ESRD). Long-term PPI users were also 28 percent more likely to suffer from CKD.

A different 2016 study associated PPI use with a 20 to 50 percent higher chronic kidney disease risk. Researchers found no similar risk for people taking H2 blockers like Pepcid or Zantac.

Acute Interstitial Nephritis (AIN)

Acute interstitial nephritis (AIN) is a kidney injury. It causes the spaces between kidney tubules to swell. Allergic reactions to PPIs may trigger AIN. AIN may occur at any point during PPI therapy.

Suffering kidney complications from a Proton Pump Inhibitor? Get a Free Case Review

In 1992, the American Journal of Medicine published an article on what is believed to be the first case of drug-induced acute interstitial nephritis due to Prilosec.

In 2004, researchers writing in the journal Nephrology, Dialysis, and Transplantation concluded Prilosec and Prevacid are the “drugs most commonly associated with interstitial nephritis.”

In 2007, other researchers writing in Clinical Nephrology identified an “ever increasing number of cases of acute interstitial nephritis associated with PPI therapy” and that “all PPIs have been documented to cause AIN.”

Despite multiple studies finding a connection between PPIs and acute interstitial nephritis, the FDA did not require manufacturers to add AIN warnings to PPI labels until 2014.

PPIs and Bacterial Infections

Gastric acid kills some harmful bacteria in the stomach. PPIs may reduce gastric acid that protects against infection.

This may cause Clostridium difficile (C. diff.) infections (CDI). The serious infections can spread if there is not enough acid to keep bacteria in check. This can lead to severe diarrhea and life-threatening inflammation of the large intestine.

In 2010, researchers published an analysis of 21 previous studies. The analysis revealed an association between PPI use and an 81 percent increased risk of C. difficile diarrhea.

In 2012, the FDA put out a safety communication saying PPI use can increase the risk for C. difficile diarrhea. And in 2014, the agency required some PPI makers to add a warning about the risk to their labels.

Researchers in a 2016 study compared twins. One twin took PPIs, the other did not. Researchers found that the twin taking a PPI had far more bacteria that can cause infections than the twin who did not take the drug.

Most recently in 2017, a study associated PPI use with a 50 percent increased risk of C. diff. infections.

PPIs and Bone Fractures

A study published in JAMA in 2006 concluded that “long-term PPI therapy, particularly at high doses, is associated with an increased risk of hip fracture.”

Several studies since 2006 have linked long-term PPI use to bone fractures. Evidence suggests PPIs decrease bone density and increase osteoporosis risk.

Since 2010, the FDA has required all PPIs to carry a warning about the risk of bone fractures of the spine, wrist and hip. The FDA found that this risk is greatest for people taking high doses for long periods of time.

“Individuals at risk for osteoporosis should have their bone status managed according to current clinical practice, and should take adequate vitamin D and calcium supplementation.”

Source: U.S. Food and Drug Administration, May 25, 2010 Safety Communication

Calcium is vital for bone strength. Research suggests that PPIs interfere with the body’s ability to absorb calcium.

A 2018 study found PPI use could cause esophageal cancer in certain patients. Researchers in Sweden looked at seven years of medical records.

They included every person given PPI therapy over a seven year period. They found that PPI use could cause as much as 5 percent of the esophageal cancers cases in the country.

Gastric Cancer Risk with PPIs

A 2017 study found that taking PPIs could double the risk of getting gastric cancer. The risk increased the longer people took the drugs. It went up five-fold for people taking PPIs for a year. The risk went up more than eight times after taking the drugs for three years.

The FDA required a gastric malignancy warning for PPIs in 2017. The agency said patients should consider follow up and testing for gastric cancer in some situations. These included early symptom relapse after taking PPIs.

In 2018, the agency added warnings for fundic gland polyps. Research has linked long-term PPI use with fundic gland polyps. These are polyps that develop in the stomach and may need surgical removal.

PPIs Can Cause Depression

A June 2018 JAMA investigation found one-third of Americans take medicines that have depression as a side effect. PPIs are one of them.

“The more of these medications you’re taking, the more likely you are to report depression,” study author Mark Olfson told NPR.

“The [JAMA] study is an important reminder that all medicines have risks, and most medicines have rare but serious risks — yet another reason that even commonly used medicines such as beta-blockers or proton pump inhibitors should not be used cavalierly”

Source: Dr. Caleb Alexander, Co-director, Center for Drug Safety and Effectiveness at Johns Hopkins Bloomberg School of Public Health, to The New York Times

PPIs and Heart Attacks

Recent studies have associated PPI use with life-threatening heart problems.

A 2017 study in PLOS One looked at PPI use by people with coronary artery disease (CAD). They found an association between PPI use and heart failure and death. The risks were greater for people who took higher doses.

A 2015 study found PPI use could increase the risk of heart attacks by 16 to 20 percent.

“These drugs may not be as safe as we think,” the study’s senior author Dr. Nicholas Leeper said.

The FDA in 2011 added a warning to PPI labels about the risk of low magnesium levels (hypomagnesemia). Low magnesium levels can cause irregular heartbeat (arrhythmias). Patients may not always exhibit symptoms.

PPIs and Strokes

A 2016 study found proton pump inhibitor use may increase stroke risk. Researchers reviewed medical records of 244,000 people in Denmark. They found PPI users faced a 21 percent increased stroke risk.

The risk varied by the type of PPI people took. Prevacid (lansoprazole) users faced a 30 percent higher risk. People taking Protonix (pantoprazole) faced a 94 percent higher stroke risk.

PPIs Linked to Premature Death

A 2017 study that found PPI use increased a person’s chance of dying within five years.

Researchers looked at more than 350,000 people’s medical records. They found people taking prescription PPIs for a year or more had a 50 percent increased risk of dying.

“No matter how we sliced and diced the data from this large data set, we saw the same thing: There’s an increased risk of death among PPI users.”

Source: Dr. Ziyad Al-Aly, study author, Washington University School of Medicine assistant professor

Can PPIs Cause Dementia?

Recent studies have been unable to show a connection between PPI use and dementia. A 2016 study from Germany drew an association between PPI use and dementia.

But at least four studies since 2016 have found no link between PPIs and dementia.
  • A 2018 study compared 7,800 middle-aged twins. Researchers found no significant changes in mental skills based on PPI use.
  • A 2017 study responded directly to the German research. It was unable to reach the same conclusion about a PPI association with dementia.
  • Another study in 2017 found women PPI users were at a lower risk of cognitive decline.
  • A third 2017 study tested 10,000 volunteers over six years. Researchers found no dementia link to PPI use.

The FDA in 2014 warned that patients who have taken PPIs for more than three years are at risk of vitamin B12 deficiency. Dementia could be a symptom of low vitamin B12.

PPI Risks for Children and Infants

In 2011, the Journal of Pediatrics looked at PPI prescribing for infants. It found the practice was widespread. The journal warned it was a growing problem. Studies since then have added evidence to that warning.

In 2018, the American Academy of Pediatrics cautioned against PPIs for preterm infants. These are infants born three weeks or more premature. The AAP published a clinical report. It called PPIs “largely ineffective” for preterm infant GERD.

“[A] lack of evidence of efficacy together with emerging evidence of significant harm…strongly suggest that these agents should be used sparingly, if at all, in preterm infants.”

Source: Dr. Eric C. Eichenwald, American Academy of Pediatrics, June 18, 2018

Another study in 2017 found a childhood fracture risk with PPIs. It looked at children given PPIs before their first birthday. Researchers looked at 874,000 American children. They found those who took PPIs as an infant had a 22 percent higher risk of childhood bone fractures.

Pregnancy and PPI Risks

A 2017 study looked at children whose mothers took PPIs during pregnancy. It found their children faced a 30 percent higher risk for asthma.

The FDA recommends pregnant and nursing women talk with their doctor about PPI alternatives.

Have you experienced serious complications as a result of long-term PPI use? Get a Free Case Review

Pneumonia Risk in Older Adults

Studies link PPI use to an increased risk of developing pneumonia.

The most recent study found that adults who take PPIs for longer than one year have an 82 percent greater risk of developing pneumonia than adults who don’t take the drugs.

Researchers say this is because PPIs reduce stomach acid that helps the body defend against ingested bacteria.

Common PPI Side Effects

The most common PPI side effects are minor. At least one percent of PPI users report common side effects. They usually do not disrupt a patient’s daily activities.

The most common side effects of proton pump inhibitors are
  • Constipation
  • Diarrhea
  • Headache
  • Itching
  • Nausea
  • Stomach pain
  • Vomiting

Stopping PPI Use Can Cause Symptom Rebound

It can be difficult to stop taking proton pump inhibitors once people start. Stopping suddenly may cause the original heartburn symptoms to return. They can sometimes come back worse than before.

People should never stop taking PPIs without talking to their doctor first. A doctor can work out a safe strategy to let a patient “step down” from PPIs.

Please seek the advice of a medical professional before making health care decisions.

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