PPIs Linked to Dangerous Complications

Some of the most commonly used prescription and over-the-counter heartburn medicines in the United States — a class of drugs that includes Nexium, Prilosec, and Prevacid, among many others — have been observed to increase risk of several kidney problems that can require dialysis or result in patient death.

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The first proton pump inhibitors (PPIs) received U.S. Food and Drug Administration (FDA) approval in 1989. In 2006, global spending on PPIs was estimated at more than $14 billion and by 2016, an estimated 15 million Americans were using PPIs.

Studies have found multiple PPI-related health risks. Some of the most serious include:

  • Chronic kidney disease (CKD)
  • Acute kidney injury (AKI)
  • Acute interstitial nephritis (AIN)
  • End-stage renal disease (ESRD)

If you have been diagnosed with any of these conditions after taking PPIs, you may benefit from talking to an attorney. Weitz & Luxenberg’s Drug and Medical Device Litigation unit has decades of experience in the complex field of pharmaceutical product liability litigation.

How Can Heartburn Medicines Cause Health Problems?

In adults, PPIs are indicated for stomach acid-related conditions including:

  • Healing erosive esophagitis (EE)
  • Gastroesophageal reflux disease (GERD)
  • Gastric and duodenal ulcers
  • Zollinger-Ellison syndrome — a rare disorder in which a person develops tumors in the pancreas or duodenum, causing the body to produce excessive stomach acid, causing duodenal or other small intestine ulcers

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There are both prescription versions of PPIs and over-the-counter (OTC) versions. Studies have found prescription PPIs are often overprescribed or prescribed for patients without an appropriate cause for which the drug is intended (indicated for).

The FDA has said that while over-the-counter PPIs “are only intended for a 14 day course of treatment up to 3 times per year,” the agency “acknowledges that consumers, either on their own, or based on a healthcare professional’s recommendation, may take these products for periods of time that exceed the directions on the OTC label.”

A 2016 study found that longer use of PPIs increased patients’ risk of developing kidney problems. Researchers compared risks among those patients taking PPIs for 30 days or fewer to those taking the drugs for as long as 720 days. The researchers found longer duration of PPI use yielded increased risk of newly diagnosed chronic kidney disease and end-stage renal disease. 

If you have been diagnosed with chronic kidney disease, acute kidney injury, interstitial nephritis, or end-stage renal disease after taking PPIs such as Nexium, Prilosec, or Prevacid, Weitz & Luxenberg would like to hear from you. You may be entitled to compensation.

What Are Proton Pump Inhibitors (PPIs)?

Stomach acid is produced by glands — proton pumps — in the stomach’s lining. PPIs reduce (inhibit) the amount of acid they produce. PPIs on the market in the U.S include:

  • Nexium (esomeprazole)
  • Prilosec (omeprazole)
  • Prevacid (lansoprazole)
  • Dexilant (dexlansoprazole)
  • Zegerid (omeprazole )
  • Protonix (pantoprazole)
  • AcipHex (rabeprazole)

Prilosec OTC, Zegerid OTC, Nexium 24HR, and Prevacid 24HR are over-the-counter versions of their prescription counterparts. AcipHex, AcipHex Sprinkle, Nexium, Nexium IV, Prevacid, Prilosec, and Protonix have also been approved for use by the FDA via prescription in children of varying age ranges.

Chronic Kidney Disease Risk

While studies of PPI use have found increased risks of several medical issues including strokes , dementia, certain infections, pneumonia, and bone fractures, many studies have also examined PPI use and the risk of kidney problems.

This includes studies that have looked at the connection to chronic kidney disease (CDK) that the National Institutes of Health (NIH) defines as “[a]ny condition that causes reduced kidney function over a period of time.” CKD may take years to develop and can lead to end-stage renal disease (ESRD). Patients who develop ESRD require dialysis or a kidney transplant to survive.

“You can treat and hopefully cure infections. Fractures can heal, though they can be catastrophic events for older people, but chronic kidney disease doesn’t go away.” Dr. Adam Schoenfeld, an internal medicine resident at the University of California, San Francisco, told The New York Times in 2016. 

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Dr. Schoenfeld co-wrote an editorial in JAMA Internal Medicine, one of the journals affiliated with the American Medical Association, commenting on a study published in the same issue in 2016, which examined PPI use and the risk of CKD. In that study, researchers found people who were on PPIs, when compared with those who were not, had statistically significantly higher risk of developing chronic kidney disease, and twice-daily dosing was linked with higher risk than once-daily dosing.

It was one of at least three studies published that year drawing a connection between PPIs and CKD.

Another of these 2016 studies found a statistically significantly “increased risk of development of CKD and death” among subjects using PPIs and concluded “healthcare providers need to be better educated about the potential side effects of these medications.”

A third study from 2016 found that patients who took PPIs faced a statistically significant 96% increase in the risk of ESRD and a statistically significant 28% increase in the risk of CKD compared to patients who used H2 (histamine 2) blockers for acid-related indications. H2 blockers are a different class of drugs that reduces stomach acid, and includes brand-name products such as Tagamet, Pepcid AC, and Zantac, among others.

Researchers in that study analyzed databases from the U.S. Department of Veterans Affairs (VA), comparing 173,321 patients who were new users of PPIs with 20,270 people who were new users of H2 blockers.

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Studies Find Increased Risks of AIN, Acute Renal Failure, and ESRD among PPI Users

Researchers began documenting problems with PPIs shortly after the first drug hit the market.

In 1992, just three years after Prilosec (omeprazole) received FDA approval, an article appeared in The American Journal of Medicine detailing what the authors believed was the first case of acute interstitial nephritis (AIN) caused by a PPI.

Proton pump inhibitors have been found to be the most common cause of drug-induced acute interstitial nephritis. AIN is responsible for up to 15% of hospitalizations for acute renal failure, but its clinical symptoms may be subacute and go undiagnosed while damage is still being done to the kidneys.

In the 1992 case, a 74-year-old woman was admitted to the University of Arizona Health Sciences Center suffering from acute renal failure after taking Prilosec for six months. Taken off her medications she recovered, but AIN symptoms returned after only two doses when she began taking the PPI again (a phenomenon known as “positive rechallenge”). After discontinuing the Prilosec for a second time her symptoms rapidly resolved again (a phenomenon known as “positive dechallenge”). The authors wrote that doctors prescribing the then fairly new medicine “should be aware of the association of acute interstitial nephritis with omeprazole.” Consult your doctor before stopping any prescribed medication.

In December, 2014, the FDA required the addition of a warning about AIN on all PPI labels. Between the time of publication of the first case report to the addition of a warning regarding AIN, dozens of additional articles in the medical journals appeared connecting PPIs to adverse kidney outcomes.

More recently published studies include one that appeared in the journal BMC Nephrology in 2013 that looked at 184,480 patient records. The researchers found people identified as having renal disease were statistically significantly more likely to have used a PPI, and concluded, “Patients with a renal disease diagnosis were twice as likely to have used a previous prescription for a PPI.”

A 2016 study found PPIs statistically significantly increased the risk of ESRD for patients with existing renal diseases (who had not been previously diagnosed with ESRD). The study looked at 3,808 patients who developed ESRD with a prior diagnosis of kidney diseases, including “nephritis, nephritis syndrome, glomerulonephritis, nephropathy, chronic kidney disease…renal function impairment…and GERD and/or peptic ulcer diseases.” These were matched with 3,808 control subjects who also had any of these diagnoses but did not progress to ESRD, and the researchers found “a significantly higher risk of ESRD” among patients with renal disease taking PPIs.

PPIs: Overprescribed and Overused?

By 2013, Prilosec OTC’s marketing campaign featured the tagline: “One pill each morning. 24 Hours. Zero heartburn.” In 2000, AstraZeneca, the manufacturer of Prilosec, received a letter from the FDA’s Division of Drug Marketing, Advertising and Communications (DDMAC) regarding an advertisement for Prilosec that the FDA said “contains audio representations and suggestions about Prilosec yet fails to include information relating to Prilosec’s major side effects and contraindications.” DDMAC asked AstraZeneca to “immediately cease using this advertisement and all other promotional materials for Prilosec that contain the same or similar presentations.”

At least one study that examined proton pump inhibitor prescriptions noted “[e]vidence from several Western studies has shown an alarmingly high and inappropriate rate of prescription of proton pump inhibitors (PPIs), which may be associated with increased healthcare costs and adverse outcomes.”

The researchers recommended doctors review indications for use each time they had contact with patients.

Another study that examined the overutilization of PPIs noted “[p]otential consequences of prolonged PPI therapy include hypergastrinemia, enterochromaffin-like cell hyperplasia, and parietal cell hypertrophy, leading to rebound acid hypersecretion.”

Another 2014 article asserted, based on a review of other studies, that PPIs were “being overprescribed worldwide in both primary and secondary care.” The authors estimated between 25% and 70% of people taking PPIs had “no appropriate indication.” They estimated “almost £2bn [$2.05 billion at the time] worldwide is being spent unnecessarily on proton pump inhibitors each year.”

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