Millions of people worldwide take prescription proton pump inhibitors including Prilosec or Nexium to treat gastroesophageal reflux disease (GERD), Barrett’s Esophagus and other esophageal erosion, H. pylori infection, and stomach (gastric) ulcers.

Proton Pump Inhibitor (PPI) Medicines, Including the Commonly Prescribed medications Prevacid, Prilosec, and Nexium, are Associated with Increased Risk of Death

In a prominent study published in BMJ in May of 2019, researchers concluded that “Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer.”

PPIs List

  • Aciphex
  • Dexilant
  • Kapidex
  • Nexium
  • Prevacid
  • Prilosec
  • Protonix
  • Zegerid

Proton Pump Inhibitor Side Effects

Unfortunately, according to the Journal of Neurogastroenterology and Motility, long-term use of these medications may lead to serious side effects including:

  • Pneumonia
  • Cerebral Ischemic Diseases (Strokes)
  • Ischemic Cardiac Diseases
  • Acute Interstitial Nephritis
  • Chronic Kidney Disease
  • Collagenous Colitis
  • Bone Fractures
  • Hypomagnesium
  • Gastric Infection
  • Colon Cancer
  • Gastric Polyps
  • Gastric Cancer
  • Hepatic Encephalopathy
  • Small Intestinal Bacterial Overgrowth
  • Spontaneous Bacterial Peritonitis
  • Changes in Gut Microbiome
  • Dementia
  • Iron Deficiency
  • B12 Deficiency
  • Drug Interaction

PPI Warnings & Studies

[11-20-2017] Increased risk of oesophageal cancer.

The long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma. This population-based cohort study included all 796,492 adults exposed to maintenance therapy with PPIs in Sweden in 2005–2012

[06-01-2017] Increased risk of gastric cancer.

Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. This study was based on a territory-wide health database of Hong Kong. We identified 63,397 adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012.

[02-22-2017] Increased risk of chronic kidney damage.

A study evaluating the use of PPIs in 125,000 patients indicates that more than half of patients who develop chronic kidney damage while taking the drugs don’t experience acute kidney problems beforehand.

[01-19-2017] Increased risk of cardiovascular events.

Proton-pump inhibitors (PPIs) seem to increase the incidence of cardiovascular events in patients with coronary artery disease (CAD), mainly in those using clopidogrel. This study followed 706 patients with CAD. Primary outcome was the combination of secondary outcomes. Secondary outcomes were 1) acute ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and 2) heart failure (HF) or death.

[12-11-2013] Risk of vitamin B12 deficiency.

A study found an association between the use of PPIs and H2RAs for 2 or more years and a subsequent diagnosis of vitamin B12 deficiency.

[02-08-2012] Increased risk of Clostridium difficile–associated diarrhea (CDAD).

The U.S. Food and Drug Administration (FDA) is informing the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve.

[3-2-2011] May cause low serum magnesium levels.

The U.S. Food and Drug Administration (FDA) is informing the public that prescription proton pump inhibitor (PPI) drugs may cause low serum magnesium levels (hypomagnesemia) if taken for prolonged periods of time (in most cases, longer than one year). In approximately one-quarter of the cases reviewed, magnesium supplementation alone did not improve low serum magnesium levels and the PPI had to be discontinued.

[05-25-2010] Increased risk of fractures of the hip, wrist, and spine.

The U.S. Food and Drug Administration (FDA) is revising the prescription and over-the-counter (OTC) labels for a class of drugs called proton pump inhibitors to include new safety information about a possible increased risk of fractures of the hip, wrist, and spine with the use of these medications.

Lawsuits & Litigation

In 2016, the first lawsuit against AstraZeneca for an alleged connection between their proton pump Inhibitor drug, Nexium, and the development of kidney disease after long term use of the drug. Though that case was subsequently withdrawn, more lawsuits have been filed against AstraZeneca, Teva, Takeda, and Pfizer alleging a connection between use of this class of medication and kidney disease and/or bone fractures. Lawsuits have also been initiated and won by the U.S. Federal Government for illegal business practices including overcharging Medicaid, misbranding, and receiving kickbacks.

To Date, there have been more than 14,000 lawsuits filed against the pharmaceutical manufacturers that make PPIs. The remaining more than 13,000 pending lawsuits have been combined into a multidistrict (MDL) litigation and the trial is scheduled to start September 21, 2020. These cases claim that patients have experience serious kidney disease complications as a result of taking PPIs. These complications have included kidney injury, failure, and acute interstitial nephritis.

Notable Proton Pump Inhibitor Lawsuit Settlements

  • 2016 – Underpaid Drug Rebates to Medicaid – Protonix – Wyeth & Pfizer – $784 Million
  • 2015 – Misleading Advertising Claim – Nexium & Prilosec – AstraZeneca – $20 Million
  • 2015 – Receiving Kickbacks – Nexium, Prilosec, Toprol XL & Plendil – AstraZeneca – $7.9 Million
  • 2012 – Promoting Off Label Use – Protonix – Pfizer – $55 Million

Medical References:

  1. BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l1580 (Published 30 May 2019)
  2. Journal of Neurogastroenterology and Motility 2018; 24(2): 182-196  https://doi.org/10.5056/jnm18001
  3. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169826
  4. http://cmajopen.ca/content/3/2/E166.full
  5. https://www.sciencedaily.com/releases/2017/02/170222082252.htm
  6. https://www.sciencedirect.com/science/article/pii/S1877782118300687?via%3Dihub
  7. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wrist-and-spine-use-proton-pump
  8. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-low-magnesium-levels-can-be-associated-long-term-use-proton-pump
  9. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-clostridium-difficile-associated-diarrhea-can-be-associated-stomach
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110863/
  11. https://jamanetwork.com/journals/jama/fullarticle/1788456
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741979/
  13. https://www.amjmed.com/article/0002-9343%2893%2990273-R/pdf
  14. https://gut.bmj.com/content/67/1/28
  15. https://www.eurekalert.org/pub_releases/2016-11/aha-phm110316.php
  16. https://med.stanford.edu/news/all-news/2015/06/some-heartburn-drugs-may-boost-risk-of-heart-attack-study-finds.html

Legal References:

  1. https://www.justice.gov/opa/pr/pfizer-agrees-pay-55-million-illegally-promoting-protonix-label-use
  2. https://www.justice.gov/opa/pr/wyeth-and-pfizer-agree-pay-7846-million-resolve-lawsuit-alleging-wyeth-underpaid-drug-rebates
  3. https://www.justice.gov/opa/pr/astrazeneca-pay-79-million-resolve-kickback-allegations
  4. https://www.jpml.uscourts.gov/sites/jpml/files/Pending_MDL_Dockets_By_Actions_Pending-July-16-2019.pdf
  5. https://www.njd.uscourts.gov/sites/njd/files/MDL16.pdf