More than two decades ago, a new kind of drug approved to treat heartburn hit the market. Proton pump inhibitors were lauded as more effective than their predecessors with minimal side effects. Some of these heartburn meds are even available without a prescription. Years after their initial introduction, however, serious side effects linked to the drugs began to surface, including, most recently, chronic kidney disease. The following article will help you learn more about proton pump inhibitors, what they are, how they work and how they may not be as safe as once thought.
What are PPIs?
Proton Pump Inhibitors, or PPIs, are popular medications used to treat certain gastrointestinal disorders.
PPIs are some of the best-selling pharmaceutical drugs in the United States, reaching about $9.5 billion in sales last year. PPIs are also overprescribed. A study published in the Journal of the American Medical Association (JAMA) earlier this year suggests between 25 and 70 percent of prescriptions written for PPIs do not have appropriate medical indications.
What conditions do PPIs treat?
PPIs are used to treat varying conditions related to the stomach, esophagus and upper small intestine (duodenum). Different PPIs are approved by the Food and Drug Administration (FDA) to treat different conditions.
Some of the conditions treated by PPIs include:
- Acid reflux
- Gastroesophageal reflux disease (GERD)
- Frequent heartburn
Acid reflux occurs when stomach acid flows back up into the esophagus, the tube that connects the throat and the stomach. Acid reflux can cause a person to taste sour liquid at the back of his or her throat or feel a burning sensation in his or her chest (heartburn).
Gastroesophageal reflux disease
GERD is a more severe form of reflux. The most common symptom of GERD is heartburn, but other symptoms may include regurgitation of food or sour liquid, difficulty swallowing, coughing, wheezing and chest pain.
Laryngopharyngeal Reflux (LRP) can also occur in people with GERD. LRP occurs when the stomach acid backs up all the way up the esophagus into the throat.
Between one quarter and one third of U.S. adults will have GERD symptoms at some point in their lifetime. GERD is most common in adults 50 years of age or older; pregnant women are also especially susceptible to developing GERD.
Gastritis refers to a group of conditions caused by inflammation of the stomach lining. Gastritis can be caused by infection, injury, regular use of pain pills called NSAIDs and too much alcohol. Symptoms of gastritis include upper belly pain, nausea and vomiting.
Some PPIs are approved to treat certain ulcers. Ulcers are sores that can develop on the lining of the stomach (gastric ulcers), the esophagus or the small intestine (duodenal ulcers).
Symptoms of ulcers include dull pain in the stomach, nausea or vomiting, bloating, burping or acid reflux, heartburn, weight loss or not wanting to eat because of the pain, and pain that improves when you eat or drink.
Some PPIs are available without a prescription. People with frequent heartburn often turn to these over-the-counter (OTC) medications to treat their symptoms. However, PPIs work over time and usually do not provide instant relief for heartburn.
How do PPIs work?
PPIs work by reducing the amount of acid produced in the stomach. They do this by blocking the enzyme in the lining of the stomach that produces acid, called the gastric proton pump.
Most PPIs stay in the blood for about one hour, but they can reduce acid for up to 48 hours because they irreversibly bind to the proton pump enzyme. For this reason, PPIs give damaged digestive tract lining a chance to heal.
PPIs reduce acid in the stomach over time and may take days to relieve a person’s symptoms. Antacids like Alka-Seltzer and H2 blockers like Zantac do a better job of providing immediate relief for heartburn.
What are some examples of PPIs?
There are at least seven different brands of PPIs on the market today, each with a different main ingredient. They are manufactured by several different pharmaceutical companies and some are available as generics.
- Prilosec (omeprazole) – approved in 1989; manufactured by AstraZeneca Pharmaceuticals; generic equivalents available
- Prevacid (lansoprazole) – approved in 1995; manufactured by Takeda Pharmaceuticals USA; generic equivalents available
- AcipHex (rabeprazole) – approved in 1999; manufactured by Eisai Inc.; generic equivalents available
- Protonix (pantoprazole) – approved in 2000; manufactured by Wyeth Pharmaceuticals Inc.; generic equivalents available
- Nexium (esomeprazole) – approved in 2001; manufactured by AstraZeneca Pharmaceuticals; generic equivalents available
- Zegerid (omeprazole and sodium bicarbonate) – approved in 2004; manufactured by Santarus Inc.
- Dexilant (dexlansoprazole) – approved in 2009; manufactured by Takeda Pharmaceuticals USA
Prilosec, Zegerid and Prevacid are also available over the counter without a prescription. The main ingredients in the over-the counter-medications are the same as the prescription, but users are directed to only take the over-the-counter version for about 14 days every four months.
When were PPIs first approved by the FDA?
The first PPI hit the market more than 25 years ago. Manufactured through an agreement between Merck & Co. and Astra AB (now AstraZeneca), Prilosec was approved by the FDA in 1989.
Today, there are about seven PPIs sold by various pharmaceutical companies, including generic versions of brand name medications like Prilosec.
How do you take PPIs?
PPIs are available in tablets or capsules and are taken by mouth either once or twice daily. Some PPIs are also available in liquid form, like Nexium and Prilosec and powder form, like Zegerid. Different PPIs are available in different strengths, ranging from 10 mg up to 60 mg. These medications are often taken 30 minutes before the first meal of the day, though some can be taken without regard to food.
Is it safe to take PPIs while pregnant or breastfeeding?
Heartburn and acid reflux are common during pregnancy. None of the PPIs currently on the market have been proven safe for use in pregnant women. However, not all PPIs are in the same pregnancy category as determined by the FDA.
Prevacid (lansoprazole), Protonix (pantoprazole), AcipHex (rabeprazole) and Dexilant (dexlansoprazole) are pregnancy category B drugs, meaning studies in animals have failed to demonstrate a risk to the developing fetus, but there are no adequate or well-controlled studies in pregnant women.
Prilosec (omeprazole), Nexium (esomeprazole) and Zegerid (omeprazole and sodium bicarbonate), on the other hand, are in the pregnancy category C. Animal studies have shown adverse effects on the fetus when exposed to these drugs, and there are no adequate or well-controlled studies in pregnant women.
Doctors may advise pregnant women to continue taking their PPI prescription, even if the drug is a category C, if the benefits outweigh the risks.
Nursing mothers should take into account that most PPIs have been shown to pass through breast milk. Nursing mothers should talk to their doctors about the benefits and risks of breastfeeding and taking PPIs.
What side effects are associated with PPIs?
The side effects of PPIs may vary from drug to drug. Some of the most common side effects include:
- Abdominal pain
- Joint pain
- Dry mouth
The long-term use of PPIs has been associated with other adverse effects, including vitamin B12 deficiencies (stomach acid is needed to absorb the vitamin).
Serious side effects
The use of PPIs has been linked to potentially serious side effects, prompting action from the FDA in some cases. These side effects include low magnesium levels in the body, Clostridium difficile-associated diarrhea, bone fractures and chronic kidney disease.
The FDA also looked into claims that two PPIs could increase a person’s risk for cardiac events. After analyzing studies and other safety data, the agency concluded in 2007 that it was not likely Prilosec and Nexium increased a person’s risk for heart problems.
What is Chronic Kidney Disease?
Chronic Kidney Disease, or CKD, is a potentially life-threatening disease that has been linked to the use of PPIs.
CKD is the gradual loss of kidney function over time. CKD can lead to kidney failure and death if not diagnosed and treated early. About 26 million Americans suffer from CKD, according to the National Kidney Center.
The kidneys are bean-shaped organs located near the middle of the back below the rib cage. The kidneys filter waste and extra water from the blood and convert it into urine. When the kidneys stop working properly, toxic waste can build up in the blood and cause serious health problems. Severely reduced kidney function can lead to kidney failure and death.
What are the symptoms of Chronic Kidney Disease?
CKD is not always diagnosed right away because the signs and symptoms are subtle and start gradually. Some signs and symptoms of CKD include:
- Changes in urination including urinating more frequently or in greater amounts; urinating less frequently or in smaller amounts; having foamy or bubbly urine or blood in urine; difficulty urinating
- Swelling in legs, feet, face or hands
- Skin rash/itching
- Leg, back or side pain
- Metallic taste in mouth or ammonia breath
- Nausea and vomiting
- Feeling cold
- Shortness of breath
- Dizziness and trouble concentrating
How do PPIs cause chronic kidney disease?
Recent studies have indicated an increased risk of kidney disease in patients taking PPIs over a long period of time.
A study published in the Journal of the American Medical Association (JAMA) earlier this year found patients taking PPIs were 20 to 50 percent more likely to develop chronic kidney disease (CKD) than those not taking PPIs.
Researchers suggest PPIs may cause inflammation in the kidneys which can cause damage over time. Short-term use of PPIs has been linked to a kidney disorder called acute interstitial nephritis, in which the spaces between the kidney tubules become swollen or inflamed. Repeated bouts of the condition could lead to CKD, say researchers.
PPIs have also been linked to magnesium deficiency in the body, which can cause kidney damage.
Has the FDA issued any warnings about PPIs?
The FDA has issued numerous safety warnings concerning PPIs. Some of those warnings encompass the entire PPI drug class, while others concern only one or two specific PPIs.
Despite recent studies linking PPIs to chronic kidney disease, the FDA has not issued a safety warning regarding the possible risk. The FDA has issued safety warnings about other serious, potentially life-threatening conditions associated with PPI use.
Prilosec, Nexium and the risk of cardiac events
In 2007, the maker of Prilosec and Nexium sent data from two different studies that showed a potential increased risk of cardiac events in patients taking the drugs. The studies raised concerns about whether longterm use of the drugs increased a person’s risk for heart attack, heart failure, and heart-related sudden death. After reviewing both studies and other information sent in by the manufacturer AstraZenica, the FDA concluded it was unlikely the two PPIs increased a person’s risk for heart-related problems.
Despite the FDA’s findings, a Stanford University study published in 2015 found a 16- to 21-percent increased risk for heart attack in patients taking PPIs.
Risk for bone fractures
In 2010, the FDA issued a safety warning to consumers about the risk of bone fractures while taking PPIs. The communication indicated PPIs could increase a person’s risk for fractures of the hip, wrist and spine with high doses or longterm use of PPIs. The agency required the all makers of PPIs to include an osteoporosis and fracture warning on their drugs’ labels.
The label change was not extended to over-the-counter PPIs because the risk is associated with high doses of PPIs not available over the counter and longterm use of PPIs, usually one year or more. Over-the-counter PPIs are intended to be used for only two weeks at a time and no more than three times per year.
Low magnesium levels
In 2011, the FDA issued a safety announcement regarding the possible risk of low magnesium levels when taking PPIs for long periods of time, usually one year or longer.
In one-quarter of the cases reviewed by the agency, magnesium supplements did not improve low magnesium levels and patients had to stop taking the drugs.
Low magnesium levels can lead to serious adverse events, including muscle spasms, irregular heartbeat and convulsions or seizures.
The agency required the makers of PPIs to include the risk of low magnesium on their drugs’ labels.
Clostridium difficile-associated diarrhea
In 2012, the FDA warned PPIs were associated with an increased risk of Clostridium difficile-associted diarrhea (CDAD). The agency required the makers of PPIs to include the risk on the drugs’ labels.
Clostridium difficile is a bacterium that can cause diarrhea that does not improve. Symptoms of the condition include watery stool, abdominal pain and fever. It may also cause patients to develop more serious intestinal conditions.
Have PPIs been recalled?
No. The FDA has not issued a recall of PPIs, nor have any manufacturers initiated a voluntary recall of the drugs, due to their potential to cause chronic kidney disease or other potentially adverse effects.
Are there lawsuits against the makers of PPIs?
People who took PPIs and suffered kidney damage are beginning to file lawsuits against the makers of these drugs. The legal system can often help people recoup the significant medical and emotional costs caused by a drug’s serious side effects.
If you or a loved a loved one took a proton pump inhibitor, such as Nexium or Prilosec, and suffered serious kidney damage, you may be entitled to compensation. Call the Hood National Law Group today for a free case evaluation. The lawyers and attorneys at Hood National Law Group have been holding pharmaceutical companies responsible for the pain and suffering they’ve inflicted on consumers for decades. Call 1-800-214-1010 today or use the form on the right-hand side of your screen.