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Proton Pump Inhibitor Side Effects

Proton Pump Inhibitors, like Nexium and Prilosec, have been linked to an increased risk of side effects such as pneumonia, fractures and kidney damage. Kidney injuries can lead to severe complications.

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Heartburn medication is a fairly common drug, available by prescription or over-the-counter (OTC). Proton pump inhibitors, one class of drugs used for treating acid reflux, is associated with side effects ranging from fracture to kidney disease. The type of PPI used and the length of time a patient has been taking it can impact the risk of adverse events.

PPI Side Effects

Many people take proton pump inhibitors (PPIs) to alleviate acid reflux, or to treat a stomach ulcer or damage to the lower esophagus resulting from acid reflux. Some of these people experience side effects from taking heartburn medication. Some of the most common side effects include:

• Headache
• Nausea
• Diarrhea
• Constipation
• Itching 1

Using proton pump inhibitors over a long period of time may pose more serious risks for some people. These risks include:

• Infections
• Bone fractures 2

Warnings When Taking PPI

If you are pregnant or breast feeding, you should check with your health care provider before taking a proton pump inhibitor. In addition, if you are taking other medications, it’s best to consult with your doctor to make sure taking a PPI would be safe. 3

Proton pump inhibitors may change how other medications are processed in your body. For example, some blood thinners, such as clopidogrel (Plavix) and warfarin (Coumadin), and anti-seizure medications may work differently if you are also taking a proton pump inhibitor. 4

FDA Issues Safety Announcements about Proton Pump Inhibitors

Symptoms of Hypomagnesemia

Some of the danger signs of low serum magnesium levels include:

  • Muscle spasm

  • Irregular heartbeat or palpitations

  • Convulsions

In recent years, the U.S. Food and Drug Administration (FDA) has issued a number of safety announcements regarding proton pump inhibitors. 5 The FDA and the manufacturers of proton pump inhibitors have yet to issue any recalls of the drugs.

Low Serum Magnesium Levels

In 2011 the FDA informed the public “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 … the PPI had to be discontinued.” 6

Clostridium Difficile–Associated Diarrhea

In 2012 the FDA informed the public that PPIs “may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD).” Clostridium difficile (or C. difficile) is a type of “bacterium that can cause diarrhea that does not improve.” In some patients, the condition can develop into more serious intestinal conditions. 7

Symptoms of Clostridium Difficile

Some of the danger signs of clostridium difficile-associated diarrhea include:

  • Watery stool

  • Abdominal pain

  • Fever

Increased Risk of Fractures of the Spine, Hip and Wrist

In 2010 the FDA informed the public it was revising prescription PPI labeling to “include new safety information about a possible increased risk of fractures of the hip, wrist, and spine with the use of these medications.” It noted patients who took a prescription proton pump inhibitor for a year or more or those who received the highest doses of PPIs were at the “highest risk for fractures” based on the FDA’s review of available data. 8 The current label states that “Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the conditions being treated.” 9

Kidney Complications from PPIs

Several studies have indicated that taking a proton pump inhibitor may be associated with a heightened risk of developing kidney damage. Specifically, kidney problems that have been linked to PPIs include: chronic kidney disease (CKD), acute kidney injury (AKI), also known as acute renal failure, interstitial nephritis, and end-stage renal disease, also called end-stage renal failure. 10

A study published in April 2015 in CMAJ Open found more than a doubling of the risk of acute kidney injury in people taking PPIs and a tripling of the risk of acute interstitial nephritis. A study published in JAMA Internal Medicine in February 2016 found a 50 percent increased risk of being diagnosed with chronic kidney disease with PPI use.

A study published in BMC Nephrology in 2013 reported that those with acute kidney injury were 72 percent more likely to have used a PPI than those who did not have acute kidney injury. A study published in April 2015 in CMAJ Open found more than a doubling of the risk of acute kidney injury in people taking PPIs and a tripling of the risk of acute interstitial nephritis. A study published in JAMA Internal Medicine in February 2016 found a 50 percent increased risk of being diagnosed with chronic kidney disease with PPI use. A study published in April of 2016 in the journal Medicine found use of a PPI to be associated with an almost doubling of the risk of end-stage renal disease. 11

Long-term Kidney Damage

Chronic kidney disease happens gradually and can worsen over time, acute kidney injury typically occurs quickly over several hours or days, interstitial nephritis — a type of kidney inflammation — can lead to permanent kidney damage, and end-stage renal disease typically requires treatment with dialysis or kidney transplant. 12

Kidneys filter waste products and eliminate extra fluid from the blood, among other functions such as helping maintain the body’s chemical balance, controlling blood pressure and producing hormones. When the kidneys are damaged, waste products and fluid can build up in the body, among other potential problems. 13

Any kidney damage can be serious, and immediate care may be required. Untreated, an individual may need to undergo kidney dialysis or a kidney transplant. In worst-case scenarios, a person can die from irreparable kidney damage or other problems, such as cardiovascular complications, resulting from kidney problems. 14

Symptoms of Kidney Damage

As waste products and excessive fluid accumulate in the body, an individual can experience other life-threatening complications to other organ systems, among other potential problems. These complications may include heart failure, heart arrhythmias and lung-related problems. 15

Initial declines in kidney function may not produce any symptoms, and even kidney failure can remain asymptomatic until kidney function significantly decreases. The symptoms of kidney damage may include:

• Chest pain, if fluid accumulates around the heart
• Shortness of breath, if fluid accumulates in the lungs
• Swelling of lower extremities or bone pain
• Fatigue, sleep problems, weakness or headaches
• Nausea, vomiting, loss of appetite or hiccupping
• Decreased mental sharpness
• Changes in urine excretion
• Muscle twitches and cramps
• High blood pressure (hypertension) that is hard to control
• High blood potassium levels (hyperkalemia) 16

  1. https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000381.htm 

  2. https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000381.htm 

  3. https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000381.htm  

  4. https://www.nlm.nih.gov/medlineplus/ency/patientinstructions/000381.htm  

  5. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm213259.htm  

  6. http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm 

  7. http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm 

  8. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm 

  9. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm; http://www.fda.gov/downloads/Drugs/NewsEvents/UCM399631.pdf 

  10. http://archinte.jamanetwork.com/article.aspx?articleid=2481157; http://bmcnephrol.biomedcentral.com/articles/10.1186/1471-2369-14-150; http://journals.lww.com/md-journal/Fulltext/2016/04120/Association_Between_the_Use_of_Proton_Pump.59.aspx; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571830 

  11. http://archinte.jamanetwork.com/article.aspx?articleid=2481157; http://bmcnephrol.biomedcentral.com/articles/10.1186/1471-2369-14-150; http://journals.lww.com/md-journal/Fulltext/2016/04120/Association_Between_the_Use_of_Proton_Pump.59.aspx; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571830/ 

  12. https://www.nlm.nih.gov/medlineplus/chronickidneydisease.html; https://www.kidney.org/atoz/content/AcuteKidneyInjury; https://www.nlm.nih.gov/medlineplus/ency/article/000464.htm; https://www.nlm.nih.gov/medlineplus/ency/article/000500.htm 

  13. https://www.nlm.nih.gov/medlineplus/chronickidneydisease.html 

  14. http://www.medicinenet.com/kidney_failure/page9.htm; http://www.medicinenet.com/kidney_failure/page12.htm; http://www.medicinenet.com/kidney_failure/page14.htm; http://www.medicinenet.com/kidney_failure/page15.htm; http://emedicine.medscape.com/article/238798-overview#a6 

  15. http://jasn.asnjournals.org/content/2/6/1053.abstract; http://www.ncbi.nlm.nih.gov/pubmed/18565479 

  16. http://www.mayoclinic.org/diseases-conditions/chronic-kidney-disease/symptoms-causes/dxc-20207466; https://www.nlm.nih.gov/medlineplus/ency/article/000471.htm; http://www.medicinenet.com/kidney_failure/page6.htm