Side Effects and Safety of Proton Pump Inhibitors.

PPIs appear to be safe, but there are some possible issues with long-term use.

PPIs have been widely used since Prilosec (omeprazole) was first approved in 1989. They appear to be safe medications with few side effects. In fact, only about 1 to 3 percent of people will stop their PPI treatment because of side effects. However, all medications have risks and benefits. PPIs may have long-term side effects that should be taken into account when considering treatment.

Common and Uncommon Side Effects
PPIs are well-tolerated, and some side effects may go away with continued use of the drug. However, contact your health care provider if any side effect becomes bothersome. Sometimes a change in dose or switch to another PPI may alleviate the problem. The side effects of all the different PPIs are very similar. The most common side effects include:

• Headache
• Stomach Pain
• Nausea
• Diarrhea
• Vomiting
• Gas
• Constipation

Although not common, serious allergic reactions may occur. Contact your health care provider if you experience any of the following symptoms:

• Rash
• Trouble breathing
• Face Swelling
• Throat Tightness

Do PPIs Lead to Broken Bones?
You may have heard that PPIs can cause fractures. In May 2010, the U.S. Food and Drug Administration (FDA) warned about the possible increased risk of fractures with PPI use. Information from studies suggests that PPIs may be associated with an increased risk of hip, wrist, and spine fractures. People who were at the greatest risk were those on high doses or used PPIs for at least one year or more. The FDA is recommending that prescribers consider shorter courses of treatment and lower doses as appropriate to treat a person’s condition. People at risk for osteoporosis should be monitored by their health care provider and take adequate calcium and vitamin D supplements.
Do PPIs Cause Low Magnesium Levels?
In March 2011, the FDA warned that using PPIs for more than a year may cause low magnesium levels. Symptoms of low magnesium include muscle spasms, tremors, irregular heartbeats, and seizures. However, not everyone with low magnesium will experience these symptoms.
The FDA recommends that health care professionals consider checking magnesium levels prior to therapy in people:

• Expected to be on long-term PPI therapy
• On PPI therapy plus Digoxin, diuretics, or other medications that lower magnesium

Your health care provider may also check magnesium levels periodically throughout treatment.
Do PPIs Cause Low Vitamin B12?
Stomach acid is needed to release vitamin B12 from the foods we eat. Because PPIs reduce stomach acid, it has been thought that PPIs may cause vitamin B12 deficiency. Symptoms of vitamin B12 deficiency may include:

• Weakness
• Anemia
• Numbness or tingling of hands or feet
• Memory problems
• Poor balance
• Soreness of the tongue or mouth

The information available is conflicting on whether this is a true side effect of PPI use. It appears that long-term use of PPIs may be most likely to lead to vitamin B12 deficiency in the elderly or in people with Zollinger-Ellison syndrome who are on high doses.
Do PPIs Help Prevent Cancer or Cause Cancer?
People who have uncontrolled GERD may be at risk for Barrett’s esophagus — a condition in which the cells in the esophagus change. Although it is rare, a small number of people with Barrett’s esophagus may develop esophageal cancer. PPIs are used to treat acid reflux associated with Barrett’s esophagus and may lower the risk of cellular changes in the esophagus that can lead to cancer.
On the other hand, there has been speculation that long-term treatment with PPIs may increase the risk of cancer. However, the evidence is not conclusive. More research needs to be done regarding PPI therapy and the link to cancer. However, people on long-term PPIs should be reassessed periodically to make certain the benefits from the medication continue to outweigh the risks.
Talk to Your Health Care Provider
Most medications have side effects. Some side effects are a nuisance, but may go away after continued use of the medication. Other side effects may be bothersome enough to discontinue the medication. Talk to your health care provider about what to expect with any new medication. If you are using PPIs for an extended period of time, discuss the risks and benefits of long-term use.