Last Updated December 9, 2020
Proton Pump Inhibitors (PPIs) are prescription and over-the-counter (OTC) drugs that are designed to limit the production of digestive acid in the stomach. In patients who suffer from maladies such as Gastro-Esophageal Reflux Disease (GERD), ulcers, or other digestive conditions, PPIs are a potent tool in the arsenal to combat painful symptoms. Today, there are several brands of PPIs on the market that have generated several billions of dollars for global pharmaceutical manufacturers.
Now, decades after first being introduced onto the market, questions have emerged concerning the potential for illness and disease associated with long-term PPI use. Medical journals and research professionals have raised the possibility of PPIs being linked to kidney injuries and increased risk of permanent renal failure. In 2014, the U.S. Food and Drug Administration (FDA) imposed a requirement that all PPIs carry warnings on their labels concerning a kidney-disease precursor condition known as Acute Interstitial Nephritis (AIN).
How Do PPIs Function?
PPIs are ingested and dissolve straight into the bloodstream. When they reach a certain type of acid-producing cellular tissue in the lining of the stomach, they disrupt the production of acid-pumping enzymes.
How Long Does It Take PPIs to Work?
PPIs are meant to be taken as part of a planned regimen that accrues over several weeks. They are not meant to be taken “on-demand” or to provide immediate relief like other medications such as antacids or histamine blockers.
How Many Brands of PPIs Are On The Market?
There are several brands of OTC and prescription PPI brands on the market in the United States:
What Are the Approved Uses for PPIs?
The FDA has approved PPIs for use in adults to treat: GERD; gastric ulcer risk; Helicobacter pylori; duodenal ulcers and Zollinger-Ellison syndrome. Dosages and duration for use of PPIs will depend upon the particular brand of PPI as not all brands are exactly similar or approved for all types of illness.
What Are the More Common Side Effects Associated with PPIs?
Documented side effects from PPIs use include:
- Headache
- Nausea
- Stomach Pain
- Gas
- Constipation
- Diarrhea
- Rash
- Vomiting
- Constipation
- Fever
- Cold or Flu-like Symptoms
Are There More Serious Side Effects Associated with PPIs?
There are some more serious conditions associated with PPIs where the FDA has either taken the additional step of issuing safety communications or warnings. These include:
- Acute Interstitial Nephritis (AIN)
- Hypomagnesemia
- Clostridium Difficile Associated Diarrhea (CDAD)
- Small Intestine Bacterial Overgrowth (SIBO)
- Hip/Wrist/Spinal Fracture Risk
What is Acute Interstitial Nephritis?
AIN is a kidney disorder in which the spaces between kidney tubules become inflamed and swollen. If left unchecked, AIN can deteriorate kidney function to the point where sufferers develop Chronic Kidney Disease (CKD). Long term suffering from CKD can eventually lead to End-Stage Renal Disease (ESRD) – also known as complete renal failure. ESRD requires either a kidney transplant or dialysis for continued survival.
Do PPIs Interact with Any Other Medications?
Omeprazole, the most commonly prescribed and purchased PPI is believed to interact with at least 194 other drugs on the market. If these interactions, at least 16 are believed to be serious, 132 are thought to be moderate and 46 are minor. One of the more serious drug interactions with omeprazole (and esomeprazole) involves the blood-thinner clopidogrel (also sold under the brand names: Ceruvin, Clopilet, and Plavix). Omeprazole and esomeprazole both stall the production of the enzyme CYP2C19 which is critical to the body’s ability to metabolize clopidogrel. The FDA issued a warning in 2009 asking patients taking clopidogrel to avoid taking omeprazole and esomeprazole.
Is It True That Some PPI Manufacturers Are Involved in Lawsuits?
Yes. Lawsuits alleging kidney disease and renal injuries from PPI use were initially filed in 2016. One of the first victims to file suit was Charles Bowers, a Tennessee man who took Nexium from 2003-2008 until he was diagnosed with acute kidney disease. Mr. Bowers currently undergoes kidney dialysis 3 days a week while he awaits a kidney transplant. From there, individuals filing lawsuits naming PPI manufacturers like AstraZeneca (among others) have mushroomed considerably. Cases from across the country have now been merged into single multidistrict litigation taking place in federal court in New Jersey (MDL-2789).
Sources Cited (17):
1) “The physiological background behind and course of development of the first proton pump inhibitor” https://pubmed.ncbi.nlm.nih.gov/25857639/
2) “Harvard Health Letter: Proton-pump inhibitors” https://www.health.harvard.edu/diseases-and-conditions/proton-pump-inhibitors
3) “MedlinePlus: Proton Pump Inhibitors” https://medlineplus.gov/ency/patientinstructions/000381.htm
4) “Healthline: Proton Pump Inhibitors” https://www.healthline.com/health/gerd/proton-pump-inhibitors#1
5) “The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5357248/
6) “What you should know about: PPIs” https://www.health.harvard.edu/diseases-and-conditions/what-you-should-know-about-ppis#:~:text=PPIs%20work%20by%20inhibiting%20certain,over%20a%20period%20of%20time.
7) “Proton Pump Inhibitors: Review of Emerging Concerns” https://www.mayoclinicproceedings.org/article/S0025-6196(17)30841-8/fulltext#:~:text=Although%20PPIs%20have%20had%20an,chronic%20kidney%20disease%2C%20and%20dementia.
8) “Risks of PPIs: What’s Real, What Needs More Research” https://healthblog.uofmhealth.org/digestive-health/risks-of-ppis-whats-real-what-needs-more-research
9) “Heartburn Drugs Again Tied to Fatal Risks” https://www.webmd.com/heartburn-gerd/news/20190606/heartburn-drugs-again-tied-to-fatal-risks#1
10) “Long-term Consequences of Chronic Proton Pump Inhibitor Use” https://www.medscape.com/viewarticle/820136
11) “Proton Pump Inhibitors (PPIs)” https://www.aboutgerd.org/medications/proton-pump-inhibitors-ppis.html
12) “Effects of proton pump inhibitors on gastric emptying: a systematic review” https://pubmed.ncbi.nlm.nih.gov/20012198/
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14) “Proton Pump Inhibitors (PPIs)” https://www.medicinenet.com/proton-pump_inhibitors/article.htm
15) “Proton Pump Inhibitors: Considerations With Long-Term Use” https://www.uspharmacist.com/article/proton-pump-inhibitors-considerations-with-longterm-use
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17) “Patient Tips Omeprazole: 7 things you should know” https://www.drugs.com/tips/omeprazole-patient-tips
Tracy Everhart
Tracy Everhart is the Editor for Drug Law Journal. A highly-trained and certified medical professional, Tracy is also an accomplished medical writer. After spending years on the front lines of the medical profession, Tracy now devotes her expertise and skills to researching and reporting on new drugs and devices that enter the market, as well as their side-effects and the real-life stories involved. Prior to joining Drug Law Journal, Tracy wrote for benchmark online healthcare resources focused on families and, in particular, women’s health issues. Tracy holds post-graduate degrees from both the American College of Healthcare Sciences and the Yale School of Nursing. She is also a graduate of both Hampshire College, where she studied microbiology and the University of South Carolina school of nursing.
