FDA Drug Safety Communication: FDA warns about serious bleeding risk with over-the-counter antacid products containing aspirin
The U.S. Food and Drug Administration (FDA) is warning consumers about the risk of serious bleeding when using nonprescription, also known as over-the-counter or OTC, aspirin-containing antacid products to treat heartburn, sour stomach, acid indigestion, or upset stomach. Many other products for these conditions are available that do not contain aspirin.
These widely used products already contain warnings about this bleeding risk on their labels; however, we are continuing to receive reports of this serious safety issue. As a result, we will continue to evaluate this safety concern and plan to convene an advisory committee of external experts to provide input regarding whether additional FDA actions are needed.
OTC aspirin-antacid products are sold under various trade names, including Alka-Seltzer Original, Bromo Seltzer, Medique Medi Seltzer, Picot Plus Effervescent, Vida Mia Pain Relief, Winco Foods Effervescent Antacid and Pain Relief, and Zee-Seltzer Antacid and Pain Reliever. They are also available as generic products.
Consumers should always read the Drug Facts label carefully when purchasing or taking an OTC product to treat heartburn, acid indigestion, or sour or upset stomach. If the product contains aspirin, consider whether you should choose a product without aspirin to relieve your symptoms.
Aspirin is a commonly used pain reducer and fever reducer. It is a nonsteroidal anti-inflammatory drug (NSAID) that can increase the risk of bleeding, including in the stomach and gastrointestinal (GI) tract. Ask your pharmacist if you need help reading the Drug Facts label.
If you have one or more of the following risk factors, you may have a higher chance of serious bleeding when taking aspirin-containing antacid products:
- Are 60 years or older
- Have a history of stomach ulcers or bleeding problems
- Take a blood-thinning or steroid medicine
- Take other medicines containing NSAIDs such as ibuprofen or naproxen
- Drink three or more alcoholic drinks every day
In 2009, a warning about the risk of serious bleeding was added to the labels of all OTC products that contain NSAIDs, including aspirin-containing antacid products. However, a search of the FDA Adverse Event Reporting System (FAERS) database identified eight cases of serious bleeding events associated with these products after the warning was added. All of these patients were hospitalized. Patients had underlying conditions such as the risk factors above that put them at greater risk for developing serious bleeding events (see Data Summary). The FAERS database includes only reports submitted to FDA so there are likely additional cases about which we are unaware.
Source : FDA (June 2016)
Association of Proton Pump Inhibitors With Risk of Dementia A Pharmacoepidemiological Claims Data Analysis
Willy Gomm, PhD1; Klaus von Holt, MD, PhD1; Friederike Thomé, MSc1; Karl Broich, MD2; Wolfgang Maier, MD1,3; Anne Fink, MSc1,4; Gabriele Doblhammer, PhD1,4,5,6; Britta Haenisch, PhD1
Importance Medications that influence the risk of dementia in the elderly can be relevant for dementia prevention. Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases but have also been shown to be potentially involved in cognitive decline.
Objective To examine the association between the use of PPIs and the risk of incident dementia in the elderly.
Design, Setting, and Participants We conducted a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer, Allgemeine Ortskrankenkassen (AOK). Data on inpatient and outpatient diagnoses (coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision) and drug prescriptions (categorized according to the Anatomical Therapeutic Chemical Classification System) were available on a quarterly basis. Data analysis was performed from August to November 2015.
Exposures Prescription of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.
Main Outcomes and Measures The main outcome was a diagnosis of incident dementia coded by the German modification of the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. The association between PPI use and dementia was analyzed using time-dependent Cox regression. The model was adjusted for potential confounding factors, including age, sex, comorbidities, and polypharmacy.
Results A total of 73 679 participants 75 years of age or older and free of dementia at baseline were analyzed. The patients receiving regular PPI medication (n = 2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) had a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).
Conclusions and Relevance The avoidance of PPI medication may prevent the development of dementia. This finding is supported by recent pharmacoepidemiological analyses on primary data and is in line with mouse models in which the use of PPIs increased the levels of β-amyloid in the brains of mice. Randomized, prospective clinical trials are needed to examine this connection in more detail.
Source : JAMA (April 2016)
Commonly Used Reflux and Ulcer Medication May Cause Serious Kidney Damage
Proton pump inhibitors should be used only when necessary and should not be taken long-term
• Patients who took proton pump inhibitors for heartburn, acid reﬂux, or ulcers had an increased risk of kidney function decline, chronic kidney disease, and kidney failure.
• The longer patients took the drugs, the greater their risk.
Proton pump inhibitors are widely used, overprescribed, and generally perceived as safe.
New research indicates that long-term use of certain medications commonly used to treat heartburn, acid reflux, and ulcers can have damaging effects on the kidneys. The findings come from a study appearing in an upcoming issue of the Journal of the American Society of Nephrology(JASN).
In 2013, an estimated 15 million Americans were prescribed proton pump (PPIs), which reduce gastric acid production. This number is likely an underestimate because the medications are also available over-the-counter and can be purchased without prescription.
To assess the safety of this widely used drug class, a team led by Yan Xie, MPH and Ziyad Al-Aly, MD, FASN (Clinical Epidemiology Center at the VA Saint Louis Health Care System and Washington University in Saint Louis) analyzed information from the Department of Veterans Affairs national databases. The investigators identified 173,321 new users of PPIs and 20,270 new users of histamine H2 receptor blockers, an alternative class of drugs also used to suppress stomach acid. Over 5 years of follow-up, those taking PPIs were more likely to experience kidney function decline than those taking H2 receptor blockers. PPI users also had a 28% increased risk of developing chronic kidney disease and a 96% increased risk of developing kidney failure. Furthermore, there was a graded association between duration of PPI use and risk of kidney problems, with those who took PPIs for a longer time being more likely to develop kidney issues.
The findings suggest that long-term use of PPIs may be harmful to the kidneys and should be avoided. PPI use may not only increase the risk of developing chronic kidney disease, but may also increase the risk of its progression to complete kidney failure. “The results emphasize the importance of limiting PPI use only when it is medically necessary, and also limiting the duration of use to the shortest duration possible,” said Dr. Al-Aly.” A lot of patients start taking PPIs for a medical condition, and they continue much longer than necessary.”
The results also provide insights for future investigations on drug safety. “The study serves as a model to leverage the availability of Big Data—with VA data being a prime example—and advanced analytics to determine long term safety profiles of commonly used medications and promote pharmacovigilance,” said Xie.
Study co-authors include Benjamin Bowe, MPH, Tingting Li, MD, Hong Xian, PhD, and Sumitra Balasubramanian, MS.
Disclosures: The authors reported no financial disclosures.
The article, entitled “Proton Pump Inhibitors and Risk of Incident and Progression of Chronic Kidney Disease and ESRD,” will appear online at http://jasn.asnjournals.org/ on April 14, 2016, doi: 10.1681/ASN.2015121377.
Source : Newswise (April 2016)
PPIs Tied to Increased Risk for Chronic Kidney Disease
Whether drugs actually cause CKD remains uncertain
Regular use of proton pump inhibitors appears to be linked to chronic kidney disease, but additional studies are needed to determine whether the drugs actually cause kidney damage, and, if so, how, researchers said.
In a prospective, community-based study involving more than 10,000 adults followed for a median of 14 years, baseline use of a proton pump inhibitor (PPI) was independently associated with a 20% to 50% higher risk for incident chronic kidney disease (CKD).
In a replication cohort, PPI use was associated with an increased risk for CKD in all analyses, and twice-daily dosing was associated with a higher risk (adjusted HR 1.46; 95% CI 1.28-1.67) than once-daily dosing (adjusted HR 1.15; 95% CI 1.09-1.21), researcher Morgan Erika Grams, MD, of Johns Hopkins University, Baltimore, and colleagues wrote in the journal JAMA Internal Medicine,published online Jan. 11.
"The risk was specific to PPI medications because the use of H2 receptor antagonists, which are prescribed for the same indication as PPIs, was not independently associated with CKD," the researchers wrote.
Proton pump inhibitors are among the most widely prescribed and overprescribed medications. Studies suggest that between 25% and 70% of prescriptions written for the drugs in the U.S. do not have appropriate medical indications, the researchers wrote.
They noted that since their introduction more than 2 decades ago, PPIs use has been linked to several uncommon adverse events in a series of observational studies, including pneumonia, C. difficile infection, acute interstitial nephritis, and acute kidney injury.
"When PPIs first came out they were thought of as a miracle drug with no associated side effects," said Adam Jacob Schoenfeld, MD, of the University of California San Francisco, who wrote an editorial accompanying the latest research.
"Over the years evidence has emerged which shows pretty convincingly that their use is probably associated with a number of side effects, even though these side effects are rare," he told MedPage Today. "There is no doubt that people with severe GERD benefit, but there is also no doubt that these drugs are overprescribed."
In the newly published study, the researchers used data from the NIH-fundedAtherosclerosis Risk in Communities (ARIC) study to examine the association between PPI use and incident CKD. The analysis included 10,482 study participants with estimated glomerular filtration rates of at least 60 mL/min/1.73 m2 who were followed from their baseline examinations between early 1996 and early 1999 to the end of 2011.
A replication cohort of 248,751 enrollees in the Geisinger Health System with similar estimated glomerular filtration rates were also included in the analysis.
PPI use was self-reported in the ARIC cohort and determined by outpatient PPI prescription in the Geisinger cohort. Incident CKD was defined using diagnostic codes at hospital discharge of death in the ARIC group and by sustained outpatient estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 in the Geisinger cohort.
The mean age of the ARIC cohort was 63 and 43.9% were male. At baseline, PPI users in both cohorts were more likely to be Caucasian, obese and users of antihypertensive drugs, aspirin and statins.
Among the study findings:
- In the ARIC cohort, PPI use was associated with incident CKD in unadjusted analysis (hazard ratio 1.45; 95% CI 1.11-1.90); in analysis adjusted for demographic, socioeconomic, and clinical variables (HR 1.50; 95% CI 1.14-1.96); and in analysis with PPI ever use modeled as a time-varying variable (adjusted HR 1.35; 95% CI 1.17-1.55)
- The association persisted when baseline PPI users were compared directly with H2 receptor antagonist users (adjusted HR 1.39; 95% CI 1.01-1.91) and with propensity score–matched non-users (HR 1.76; 95% CI 1.13-2.74)
- In the Geisinger cohort, PPI use was associated with CKD in all analyses, including a time-varying new-user design (adjusted HR, 1.24; 95% CI 1.20-1.28), with twice daily dosing associated with a larger risk than once daily dosing
It has been suggested that the possible impact of PPIs on acute kidney injury is mediated through acute interstitial nephritis, and Schoenfeld suggested that repeated insults from acute injury could potentially lead to chronic kidney damage.
"Obviously more studies are needed to examine this," he said. "These are relatively rare side effects."
In their editorial, Schoenfeld and UCSF colleague Deborah Grady, MD, wrote that PPIs should be prescribed cautiously to patients at high risk for kidney disease, as well as other conditions that may be linked to the drugs, including hypomagnesemia, C. difficileinfection, and osteoporotic fracture.
"In patients with symptomatic gastrointestinal reflux, ulcer disease and severe dyspepsia, the benefits of PPI use likely outweigh its potential harms," they wrote. "However, for less serious symptoms and for prevention of bleeding in low-risk patients, potential harms may outweigh the benefits."
Source : MedPage Today (January 2016)
First, Do No Harm: Hospital Patients Given Anti-Heartburn Drugs Have Higher Risk of Dying, Study Finds
U-M/VA computer model suggests that common use of acid-reducing medicine to prevent stomach bleeding increases mortality from infections
Right now, in any American hospital, about half of the patients have a prescription for an acid-reducing drug to reduce heartburn or prevent bleeding in their stomach and gut.
But that well-intentioned drug may actually boost their risk of dying during their hospital stay, a new study finds – by opening them up to infections that pose more risk than bleeding would.
In fact, according to a computer simulation based on real-world risk and benefit data, around 90 percent of hospital inpatients who were first prescribed these drugs in the hospital have a higher risk of dying when they’re taking them, compared with their risk if they hadn’t gotten the prescription.
And for around 80 percent of patients who were already on these common drugs, called proton-pump inhibitors or PPIs, when they arrived at the hospital, staying on them also may lead to a small increase in the risk of dying.
The extra risk of death comes from the fact that reducing acid in the stomach can increase the risk of infections – especially pneumonia and Clostridium difficile, both of which pose a serious risk to hospitalized patients who develop them.
The study, which uses a computer model to achieve a result that otherwise would require an impractically large clinical trial, is published in the Journal of General Internal Medicine by a team from the University of Michigan Medical School and VA Ann Arbor Healthcare System.
“Many patients who come into the hospital are on these medications, and we sometimes start them in the hospital to try to prevent gastrointestinal, or GI, bleeds,” says lead author Matthew Pappas, M.D., MPH.
“But other researchers have shown that these drugs seem to increase the risk of pneumonia and C. diff, two serious and potentially life-threatening infections that hospitalized patients are also at risk for,” he continues. “Our new model allows us to compare that increased risk with the risk of upper GI bleeding. In general, it shows us that we’re exposing many inpatients to higher risk of death than they would otherwise have – and though it’s not a big effect, it is a consistent effect.”
As a result of the new findings, he says, very few hospital patients should start taking or continue on PPIs as a preventive measure against gastrointestinal bleeding.
Pappas, a hospitalist physician at U-M with an engineering background and a VA Health Services Fellow, worked with Sandeep Vijan, M.D., MPH, who treats patients at the VAAHS and is a member of the VA Center for Clinical Management Research and U-M’s Institute for Healthcare Policy and Innovation. Pappas is a clinical lecturer, and Vijan a professor, in the U-M Medical School’s Division of General Medicine. The project’s only funding was Pappas’s fellowship support.
Cutting PPI use to cut infection risk
Pappas notes that nationally, some efforts have already shown ways to reduce the rate of new PPI prescriptions to hospitalized patients – about 20 percent of whom receive such orders right now.
But truly reducing PPI use in hospitals to the most appropriate patients – those with existing GI bleeding – will take more effort, Pappas predicts.
That’s because PPIs are built into many heuristics, or rules of thumb, that guide much hospital care. For instance, when a patient receives high-dose steroids in the hospital, the physician may automatically also prescribe a PPI to prevent the GI bleeding that steroids can cause.
“In fact, in running our simulation, we thought we would find some populations such as those on steroids or other medications often prescribed together with PPIs, who would not experience the increased mortality risk,” Pappas says. “But that turned out not to be the case.” GI bleeds are risky, it’s true. But hospital-acquired pneumonia and C. diff are much more common.
Although research is still needed on why PPI use increases a patient’s vulnerability to hospital-acquired pneumonia and C. diff infection, the effect of the acid-reducing drugs on gut bacteria likely has a direct impact. In the case of pneumonia, suppressing acid production may increase the amount of bacteria in the stomach and throat, which can then get into the lungs and cause pneumonia.
Model can be used for other risk-benefit balancing
Pappas notes that the model he developed with Vijan and recent U-M Ford School of Public Policy graduate Sanjay Jolly could be applied to many other situations where a common preventive or treatment measure in medicine also carries with it an increased risk of an unwanted effect.
Using such models, based on data from observational studies, could answer important questions in medicine without needing to carry out massive prospective clinical trials. To answer the question of whether the predicted increase in mortality risk caused by PPIs in inpatients is real, he says, would take a clinical trial of more than 64,000 patients randomly assigned to receive PPIs or not. Since PPIs are available as generic medications, the likelihood of such a study being funded and performed is nearly zero.
“Any time there are complex risk/benefit tradeoffs, without the possibility of a high-quality trial, this kind of simulation can help us come up with answers to inform clinical care,” he says.
For instance, he’s now studying the issue of “bridging” medication in patients who have been prescribed blood-thinning medications to prevent a stroke. Such patients often receive a prescription for an injected drug that will reduce stroke risk during the week or two before their regular oral drugs take effect. But that injection carries its own risk.
“Humans aren’t very good at recognizing very rare events, and reacting appropriately to things that are unlikely to happen,” says Pappas. “Physicians have an instinct to want to prevent very bad, though rare events – but everything we do carries risks. We need to be mindful of the things we are doing to prevent rare outcomes, and keep the risks in perspective. Computers can help.”
Reference: Journal of General Internal Medicine, DOI:10.1007/s11606-015-3536-7
Source : NewsWise via University of Michigan (Nov 2015)
Proton pump inhibitors are associated with increased risk of heart attack
People who take proton pump inhibitors (PPIs), commonly used drugs for heartburn, have a greater risk of suffering a heart attack whether or not they have any history of cardiovascular disease, suggests a data-mining study.
Researchers assessed data involving 16 million clinical documents on 2.9 million individuals for pharmacovigilance information.
Patients with gastro-oesophageal reflux disease who took PPIs, whose main action is to reduce the production of gastric acid, were more likely than the general population to suffer a heart attack (adjusted odds ratio 1.16; 95% confidence interval [CI], 1.09–1.24), while alternative heartburn therapies, H2 blockers, were not associated with an increased risk.
Survival analysis in a prospective cohort found a two-fold (hazard ratio 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular death.
Had the data-mining approach used in this study been available earlier, a correlation between heart attack risk and two PPIs in particular, lansoprazole and omeprazole, would have been spotted as early as 2000, wrote the study’s lead researcher Nicholas Leeper, assistant professor of surgery and medicine at the Stanford University Medical Center, and colleagues, in the journalPLOS ONE on 10 June 2015.
Previous studies have shown a link between PPIs and the risk of major adverse cardiovascular events in patients who take the antiplatelet drug clopidogrel, which is used to treat blood clots in patients with cardiovascular disease. In this latest study, the increased risk of heart attack was not affected by clopidogrel use.
Some 113 million PPI prescriptions are dispensed globally each year. About 21 million people in the United States used one or more prescription PPIs in 2009, making it the third highest seller in the country. This is the first time that an increased risk of heart attack has been found in patients who take PPIs but have no prior history of cardiovascular disease.
“Although other research has not shown such an association, the study throws up some interesting findings and certainly merits further investigation,” said Anton Emmanuel, consultant gastroenterologist at University College London Hospitals (UCLH), a spokesperson for the British Society of Gastroenterology. “There is certainly correlation; however this does not necessarily imply a causal link and therefore we must be careful about jumping to conclusions too quickly.”
“Our observation that PPI usage is associated with harm in the general population — including the young and those taking no antiplatelet agent — suggests that PPIs may promote risk via an unknown mechanism that does not directly involve platelet aggregation,” Leeper and his team write, and suggest that the mechanism may involve dysregulation of vascular nitric oxide synthase.
The study was based on patient data from two sources: Stanford’s hospital system (Stanford Translational Research Integrated Database Environment or STRIDE); and a company called Practice Fusion, which provides a free, web-based electronic health record (EHR) system for clinicians.
“Most long-term side effects aren’t caught during clinical trials, but we can now run virtual post-market clinical trials simply by analyzing a ton of real-world data (ie, millions of de-identified patient records) that physicians are collecting and entering about their patients in the secure Practice Fusion cloud,” said Justin Jones at Practice Fusion, the company that provided data on 1.1 million anonymous outpatients in the study.
There is now an enormous amount of data that could help determine if one medication is more efficacious than another. Or, as in this case, unexpectedly deleterious.
“The long-term power and value of electronic health records is largely in the massive de-identified clinical datasets like we have built and are growing rapidly,” said Jones.
Table: Proton pump inhibitor use is associated with an increased risk for heart attack
Proton pump inhibitor Odds ratio (95% CI) (derived from STRIDE data) Source: PLoS ONE
Pantoprazole 1.34 (1.16-1.55)
Omeprazole 1.26 (1.12-1.42)
Lansoprazole 1.24 (1.06-1.45)
Rabeprazole 1.12 (0.88-1.41)
Esomeprazole 1.08 (0.88-1.31)
Source : Pharmaceutical journal (June 2015)
FDA Drug Safety Communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs)
.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.Patients should immediately contact their healthcare professional and seek care if they take PPIs and develop diarrhea that does not improve.
Clostridium difficile (C. difficile) is a bacterium that can cause diarrhea that does not improve.1 Symptoms include watery stool, abdominal pain, and fever, and patients may go on to develop more serious intestinal conditions. The disease can also be spread in the hospital. Factors that may predispose an individual to developing CDAD include advanced age, certain chronic medical conditions, and taking broad spectrum antibiotics. Treatment for CDAD includes the replacement of fluids and electrolytes and the use of special antibiotics.
The FDA is working with manufacturers to include information about the increased risk of CDAD with use of PPIs in the drug labels.
FDA is also reviewing the risk of CDAD in users of histamine H2 receptor blockers. H2 receptor blockers are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and heartburn. H2 receptor blockers are marketed under various brand and generic drug names (see Tables 3 and 4) as prescription and OTC products.
Today's communication is in keeping with FDA's commitment to inform the public about the Agency's ongoing safety review of drugs. FDA will communicate any new information on PPIs or H2 receptor blockers and the risk of CDAD when it becomes available.
Additional Information for Patients and OTC Consumers:
- Seek immediate care if you use PPIs and develop diarrhea that does not improve. This may be a sign of Clostridium difficile–associated diarrhea (CDAD).
- Your healthcare professional may order laboratory tests to check if you have CDAD.
- Do not stop taking your prescription PPI drug without talking to your healthcare professional.
- Discuss any questions or concerns about your PPI drug with your healthcare professional.
- If you take an OTC PPI drug, follow the directions on the package carefully.
- Report any side effects you experience to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of the page.
- A diagnosis of CDAD should be considered for PPI users with diarrhea that does not improve.
- Advise patients to seek immediate care from a healthcare professional if they experience watery stool that does not go away, abdominal pain, and fever while taking PPIs.
- Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
- Report adverse events involving PPIs to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
FDA has reviewed reports from the FDA's Adverse Event Reporting System (AERS) and the medical literature for cases of Clostridium difficile-associated diarrhea (CDAD) in patients undergoing treatment with PPIs. Many of the adverse event reports involved patients who were elderly, had chronic and/or concomitant underlying medical conditions, or were taking broad spectrum antibiotics that could have predisposed them to developing CDAD. Although these factors could have increased their risk of CDAD, the role of PPI use cannot be definitively ruled out in these reviewed reports. Patients who have one or more of these risk factors may have serious outcomes from CDAD with concomitant PPI use.
FDA also reviewed a total of 28 observational studies described in 26 publications. Twenty-three of the studies showed a higher risk of C. difficile infection or disease, including CDAD, associated with PPI exposure compared to no PPI exposure.2-27 Although the strength of the association varied widely from study to study, most studies found that the risk of C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among patients with PPI exposure compared to those without PPI exposure. In the five studies that provided information on clinical outcomes, colectomies, and rarely deaths, were reported in some patients 4,6,11,12,21
The published studies varied in their ability to assess the association between C. difficile infection or CDAD and prior PPI use. There were limited data on the relationship between the risk of C. difficile infection or CDAD and PPI dose and duration of use. There also was little information on the use of OTC PPIs in community settings in these studies. Nevertheless, the weight of evidence suggests a positive association between the use of PPIs and C. difficile infection and disease, including CDAD.
Facts about Proton Pump Inhibitor (PPI) Drugs
- Marketed under various brand and generic drug names (see Tables 1 and 2) as prescription and over-the-counter (OTC) products.
- Work by reducing the amount of acid in the stomach.
- Prescription PPIs are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus.
- Over-the-counter PPIs are used to treat frequent heartburn.
Source FDA (Feb 2012)
Link to Source
FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors
FDA has determined an osteoporosis and fracture warning on the over-the-counter (OTC) proton pump inhibitor (PPI) medication “Drug Facts” label is not indicated at this time. Following a thorough review of available safety data, FDA has concluded that fracture risk with short-term, low dose PPI use is unlikely.
The available data show that patients at highest risk for fractures received high doses of prescription PPIs (higher than OTC PPI doses) and/or used a PPI for one year or more.
In contrast to prescription PPIs, OTC PPIs are marketed at low doses and are only intended for a 14 day course of treatment up to 3 times per year. FDA acknowledges that consumers, either on their own, or based on a healthcare professional’s recommendation, may take these products for periods of time that exceed the directions on the OTC label. Healthcare professionals should be aware of the risk for fracture if they are recommending use of OTC PPIs at higher doses or for longer periods of time than in the OTC PPI label.
Safety Announcement [05-25-2010] 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.
Proton pump inhibitors work by reducing the amount of acid in the stomach. Nexium, Dexilant, Prilosec, Zegerid, Prevacid, Protonix, Aciphex, and Vimovo are available by prescription to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus. Prilosec OTC, Zegerid OTC, and Prevacid 24HR are sold over-the-counter (OTC) for the treatment of frequent heartburn.
The new safety information is based on FDA's review of several epidemiological studies that reported an increased risk of fractures of the hip, wrist, and spine with proton pump inhibitor use. Some studies found that those at greatest risk for these fractures received high doses of proton pump inhibitors or used them for one year or more (see Data Summary section).The majority of the studies evaluated individuals 50 years of age or older and the increased risk of fracture primarily was observed in this age group.
While the greatest increased risk for fractures in these studies involved people who had been taking prescription proton pump inhibitors for at least one year or who had been taking high doses of the prescription medications (not available over-the-counter), as a precaution, the "Drug Facts" label on the OTC proton pump inhibitors (indicated for 14 days of continuous use) also is being revised to include information about this risk.
Healthcare professionals and users of proton pump inhibitors should be aware of the possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors, and weigh the known benefits against the potential risks when deciding to use them.
Additional Information for Patients and Consumers
- Proton pump inhibitors are effective in treating a variety of gastrointestinal disorders. Do not stop taking your proton pump inhibitor unless told to do so by your healthcare professional.
- Be aware that an increased risk of fractures of the hip, wrist, and spine has been reported in some studies of patients using proton pump inhibitors. The greatest increased risk for these fractures was seen in patients who receive high doses of these medications or use them longer (a year or more).
- Read and follow thedirections onthe OTC Drug Facts label, when considering use of OTC proton pump inhibitors.
- Be aware that the OTC proton pump inhibitors should only be used as directed for 14 days for the treatment of frequent heartburn. If your heartburn continues, talk to your healthcare professional. No more than three 14-day treatment courses should be used in one year.
- Talk to your healthcare professional about any concerns you may have about using proton pump inhibitors.
- Report any side effects with proton pump inhibitors to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.
Additional Information for Healthcare Professionals
- Proton pump inhibitors provide important benefits for many patients in treating or preventing conditions such as erosive esophagitis, nonsteroidal anti-inflammatory drug-induced ulcers and gastroesophageal reflux disease.
- Be aware of the increased risk of fractures of the hip, wrist, and spine seen in some observational studies in patients using proton pump inhibitors.
- When prescribing proton pump inhibitors, consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition.
- Follow the recommendations in the product labeling when prescribing proton pump inhibitors.
- Individuals at risk for osteoporosis should have their bone status managed according to current clinical practice, and should take adequate vitamin D and calcium supplementation.
- Report any adverse events with proton pump inhibitors to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.
Data SummaryTo date, randomized clinical trials of proton pump inhibitors have not found an increased risk of fractures of the hip, wrist, or spine. These studies are generally six months in duration and there is limited information on effects of higher than recommended doses.
The decision to revise the Warnings and Precautions section of the prescription labeling as well as the OTC Drug Facts label for proton pump inhibitors is based on FDA's review of the findings from seven published epidemiological studies.1-7 These studies used claims data from computerized administrative databases to evaluate the risk of fractures of the hip, wrist, and spine in patients treated with proton pump inhibitors compared to individuals who were not using proton pump inhibitors (The findings from these studies are found in the Table below).
In these studies:
- Six reported an increased risk of fractures with the use of proton pump inhibitors 1,2,3,5,6,7.
- Exposure to proton pump inhibitors ranged from a period of 1 to 12 years, depending on the study.
- The emergence of fractures varied among studies; with one study reporting an increase in fractures with use of proton pump inhibitors in the previous year 2 and another study finding an increase after 5 to 7 years of proton pump inhibitor use3.
- The increased risk of fractures was primarily observed in older individuals.
- Two studies reported an increase in fractures with higher doses of proton pump inhibitors 2,5.
- Two studies reported an increase in fractures with longer duration of use 2,3.
- One study did not find a relationship between proton pump inhibitor use and fractures 4. This study limited the study population to those without major risk factors for fracture.
Several study limitations, however, make understanding the clinical relevance of the reported findings difficult to determine. Administrative claims databases do not typically contain information on all potential factors that could influence the relationship between proton pump inhibitors use and fracture risk. These studies were not able to account for missing or incomplete information on family history of osteoporosis, smoking history, weight and height measurements, alcohol use, history of dietary and supplement use (calcium and vitamin D), OTC medication use, presence of digestive diseases, such as ulcers, reasons for proton pump inhibitor use, and recent history of immobility, dizziness, or falls. In addition, in most studies where a possible link with osteoporotic fracture was reported, no information was collected about the timing of proton pump inhibitor use in relation to onset or worsening of osteoporosis.
However, the exact mechanisms for an increased risk of fractures with proton pump inhibitor use are not known. Three epidemiologic studies found no consistent association between chronic proton pump inhibitor use and bone mineral density 6,7,8.
Based on the available data, at this time it is not clear if the use of proton pump inhibitors is the cause of the increased risk of fractures seen in some epidemiologic studies.
To further investigate this issue, the FDA plans to analyze data from several large, long-term, placebo-controlled clinical trials of bisphosphonates (drugs used to prevent fractures) to assess the risk of fractures in women at risk for osteoporosis-related fractures who used or did not use proton pump inhibitors.
FDA is also working with the manufacturers of these products to further study this possible risk. For example, as part of the Dexilant (dexlansoprazole) approval, (January 2009), the manufacturer was required to perform a postmarketing clinical trial to evaluate the effects of dexlansoprazole and esomeprazole on bone homeostasis, including changes in biomarkers of bone formation and bone resorption.The results from this trial are expected at the end of 2011.
In summary, the available data, including findings from several epidemiological studies, suggest a possible increased risk of fractures of the hip, wrist, and spine in patients using proton pump inhibitors. The data suggest that the increased risk may be dependent upon dose, duration of use, or both. At the present time, there is uncertainty about the magnitude of this risk. In light of this uncertainty, when prescribing proton pump inhibitors, healthcare professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient's condition.
SEE LINK TO SOURCE FOR TABLE
References:1. Vestergaard P, Rejnmark L, Mosekilde L. Proton pump inhibitors, histamine H2
receptor antagonists, and other antacid medications and the risk of fracture. Calcif Tissue
2. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy
and risk of hip fracture. JAMA 2006;296:2947-53.
3. Targownik LE, Lix LM, Metge CJ, Prior HJ, Leung S, Leslie WD. Use of proton pump
inhibitors and risk of osteoporosis-related fractures. CMAJ 2008 Aug 12;179(4):319-26.
4. Kaye JA, Jick H. Proton pump inhibitor use and risk of hip fractures in patients
without major risk factors. Pharmacotherapy 2008;28:951-59.
5. Corley, D.A., Kubo, A., Zhao, W., Quesenberry, C., Proton Pump Inhibitors and Histamine-2 Receptor Antagonists are Associated with Hip Fractures among At-Risk Patients, Gastroenterology (2009), doi:10.1053/j.gastro.2010.03.055.
6. Gray SL, LaCroix AZ, Larson J, Robbins J, Cauley JA, Manson JE, Chen Z. Proton Pump Inhibitor Use, Hip Fracture, and Change in Bone Mineral Density in Postmenopausal Women. Arch Intern Med 2010;170 (9):765-771.
7. Yu EW, Blackwell T, Ensrud KE, Hillier TA, Lane NE, Orwoll E, Bauer DC, et al. Acid-Suppressive Medications and Risk of Bone Loss and Fracture in Older Adults. Calcif Tissue Int. 2008;83(4):251-259.
8. Targownik LE, Lix LM, Leung S, Leslie WD. Proton-pump inhibitor use is not associated with osteoporosis or accelerated bone mineral density loss. Gastroenterology 2010;138:896-904.
Source : FDA (March 2011)
Link to Source
FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs)
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.PPIs work by reducing the amount of acid in the stomach and are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus. In 2009, approximately 21 million patients filled PPI prescriptions at outpatient retail pharmacies in the United States.2 Patients who take prescription PPIs usually stay on therapy for an average of about 180 days (6 months).3
Prescription PPIs include Nexium (esomeprazole magnesium), Dexilant (dexlansoprazole), Prilosec (omeprazole), Zegerid (omeprazole and sodium bicarbonate), Prevacid (lansoprazole), Protonix (pantoprazole sodium), and AcipHex (rabeprazole sodium). Vimovo is a prescription combination drug product that contains a PPI (esomeprazole magnesium and naproxen). Over-the-counter (OTC) PPIs include Prilosec OTC (omeprazole), Zegerid OTC (omeprazole and sodium bicarbonate), and Prevacid 24HR (lansoprazole).
In contrast to prescription PPIs, OTC PPIs are marketed at low doses and are only intended for a 14 day course of treatment up to 3 times per year. FDA believes that there is very little risk of hypomagnesemia when OTC PPIs are used according to the directions on the OTC label.
Low serum magnesium levels can result in serious adverse events including muscle spasm (tetany), irregular heartbeat (arrhythmias), and convulsions (seizures); however, patients do not always have these symptoms. Treatment of hypomagnesemia generally requires magnesium supplements. Treatment in patients taking a PPI and who have hypomagnesemia may also require stopping the PPI.
Healthcare professionals should consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment in patients expected to be on these drugs for long periods of time, as well as patients who take PPIs with medications such as digoxin, diuretics or drugs that may cause hypomagnesemia. For patients taking digoxin, a heart medicine, this is especially important because low magnesium can increase the likelihood of serious side effects. Healthcare professionals should consider obtaining magnesium levels periodically in these patients.
Information about the potential risk of low serum magnesium levels from PPIs will be added to the WARNINGS AND PRECAUTIONS sections of the labels for all the prescription PPIs.
Today's communication is in keeping with FDA's commitment to inform the public about its ongoing safety review of drugs. FDA is continuing to review reports of possible adverse events and drug interactions with PPI drugs submitted to our Adverse Event Reporting System.
[See Data Summary]
Additional Information for Patients
- Seek immediate care if you (or your child) experience an abnormal heart rate or rhythm, or symptoms such as a racing heartbeat, palpitations, muscle spasm, tremor or convulsions while taking a PPI drug. In children, abnormal heart rates may cause fatigue, upset stomach, dizziness and lightheadedness.
- Tell your healthcare professional if you have ever been told you have low magnesium levels in your blood, or if you take the drug digoxin, diuretics, or other drugs that may cause hypomagnesemia.
- Your healthcare professional may occasionally check your serum magnesium level (a blood test) while you are taking your prescription PPI drug.
- Do not stop taking your prescription PPI drug without talking to your healthcare professional.
- Discuss any questions or concerns about your PPI drug with your healthcare professional.
- If you take an over-the-counter (OTC) PPI drug, follow the directions on the package carefully.
- Make sure your healthcare professional knows if you have been taking an OTC PPI drug for a long period of time.
- Report any side effects you experience to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of the page.
- Consider obtaining serum magnesium levels prior to initiation of prescription PPI treatment and checking levels periodically thereafter for patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics).
- Hypomagnesemia occurs with both loop diuretics (furosemide, bumetanide, torsemide, and ethacrynic acid) and thiazide diuretics (chlorothiazide, hydrochlorothiazide, indapamide, and metolazone). These agents can cause hypomagnesemia when used as a single agent or when combined with other anti-hypertensives (e.g., beta-blockers, angiotensin receptor blockers and/or ACE inhibitors).
- Advise patients to seek immediate care from a healthcare professional if they experience arrhythmias, tetany, tremors, or seizures while taking PPIs. These may be signs of hypomagnesemia.
- Consider PPIs as a possible cause of hypomagnesemia, particularly in patients who are clinically symptomatic.
- Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
- Be aware that consumers either on their own, or based on a healthcare professional's recommendation, may take OTC PPIs for periods of time that exceed the directions on the OTC label. This is considered an off-label (unapproved) use. Healthcare professionals should communicate the risk of hypomagnesemia to patients if they are recommending prolonged use of an OTC PPIs.
- Report adverse events involving PPIs to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of the page.
FDA has reviewed reports from the Adverse Event Reporting System (AERS), medical literature, and periodic safety update reports for cases of hypomagnesemia in patients undergoing prolonged treatment with PPI medications. FDA's review focused on 38 cases in AERS and 23 cases reported in the literature (which include at least 8 cases of the identified AERS cases).4,5,6,7,8,9,10,11 The AERS case series excluded patients who were on diuretics. The cases from the literature included patients on diuretics when either (a) change in diuretic was not associated with an improvement in serum magnesium level, or (b) when increase in serum magnesium level occurred with documented PPI discontinuation. The FDA review suggests an association between hypomagnesemia-related serious adverse events and prolonged PPI use. However, because hypomagnesemia is likely under-recognized and under-reported, the available data are insufficient to quantify an incidence rate for hypomagnesemia with PPI therapy.
Hypomagnesemia has been reported in adult patients taking PPIs for at least three months, but most cases occurred after a year of treatment. Approximately one-quarter of these cases required discontinuation of PPI treatment in addition to magnesium supplementation. Some cases cited both positive dechallenge as well as positive rechallenge (i.e., resolution of hypomagnesemia with PPI cessation and recurrent hypomagnesemia with PPI resumption). After discontinuing the PPI, the median time required for the magnesium to normalize was one week. After restarting the PPI, the median time to develop hypomagnesemia again was two weeks. In most cases reviewed the patients did not continue on PPIs after the hypomagnesemia was treated.
Examples of positive dechallenge in two patients include a 63-year-old woman and a 67-year-old man who were both treated with PPIs for 6 and 11 years, respectively. Both patients presented with seizures and hypomagnesemia. Although both patients' hypomagnesemia partially resolved with intravenous replacement, in both cases discontinuation of PPI treatment was necessary to stop ongoing symptoms and to stop magnesium loss.
Clinically serious adverse events were consistent with commonly reported signs and symptoms of hypomagnesemia, which are similar to the signs and symptoms reported with hypocalcemia. The serious events included tetany, seizures, tremors, carpo-pedal spasm, atrial fibrillation, supraventricular tachycardia, and abnormal QT interval. Hypomagnesemia also produces impaired parathyroid hormone secretion which may lead to hypocalcemia. In cases where comprehensive clinical laboratory data were available, most patients had concomitant hypocalcemia and normal parathyroid hormone levels. Therefore, these findings confirm hypomagnesemia as the primary deficit.
The mechanism responsible for hypomagnesemia associated with long term PPI use is unknown; however, long term use of PPIs may be associated with changes in intestinal absorption of magnesium.5
OTC PPIs are marketed for the treatment of frequent heartburn under the brand names Prilosec OTC, Zegerid OTC, and Prevacid 24 HR. OTC PPIs are labeled for 14 days of use, and this treatment course may be repeated every 4 months, up to 3 times per year. FDA acknowledges that consumers, either on their own, or based on a healthcare professional's recommendation, may take these products for periods of time that exceed the directions on the OTC label. This is considered an off-label (unapproved) use, based on the directions of use for OTC PPIs. Healthcare professionals should be aware of the risk of hypomagnesemia if they are recommending use of OTC PPIs for longer periods of time than in the OTC PPI label. FDA believes that OTC PPIs carry very little risk of hypomagnesemia when used according to the package directions, and therefore the Drug Facts box for the OTC PPIs will not be changed to include the risk of hypomagnesemia.
- SDI, Vector One®: National (VONA). 2002- 2010. Data extracted 3-12-10.
- SDI, Vector One®: Total Patient Tracker (TPT). 2002-2009. Data extracted 3-24-10.
- IMS Health, IMS Health Plan Claims DatabaseTM
- Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesium induced by several proton-pump inhibitors. Ann Intern Med (Nov 17, 2009). 151(10); 755-756.
- Cundy T, Dissanayake A. Severe hypomagnesemia in long-term users of proton-pump inhibitors. Clinical Endocrinology (2008). 69; 338-341.
- Epstein M, McGrath S, Law F. Proton-pump inhibitors and hypomagnesemic hypoparathyroidism. NEJM. October 26, 2006. 355;17:1,834-1,836.
- Hoorn EJ, MD, van der Hoek J, de Man RA, Kuipers EJ, et al. A case series of proton pump inhibitor–induced hypomagnesemia. Am J Kidney Dis. February 25 2010. (epub).
- Kuipers MT, Thang HD, Arntzenius AB. Hypomagnesaemia due to use of proton pump inhibitors—a review. Neth J Med (May 2009). 67(5);169-172.
- Metz DC, Sostek MB, Ruszniewski P, Forsmark CE, et al. Effects of esomeprazole on acid output in patients with Zollinger-Ellison syndrome or idiopathic gastric acid hypersecretion. Am J Gastroenterol. (December 2007). 102(12); 2648-2654.
- Shabajee N, Lamb E, Sturgess I, Sumathipala R. Omeprazole and refractory hypomagnesemia. BMJ (2008): 337; 173-175.
- Mackay JD and Bladon PT. Hypomagnesaemia due to proton-pump inhibitor therapy: a clinical case series. QJ Med 2010; 103:387-395.
Link to source
Why You Should Get Off Prescription Acid-Reducing Drugs ASAP!
Treatment with the anti-heartburn drugs known as proton pump inhibitors (PPIs) for eight weeks induces acid-related symptoms like heartburn, acid regurgitation and dyspepsia once treatment is withdrawn in healthy individuals, according to a new study.
More than 40 percent of healthy volunteers, who had never been bothered by heartburn, acid regurgitation or dyspepsia, developed such symptoms in the weeks after cessation of PPIs.
The use of PPIs for acid-related symptoms and disorders is extensive and rapidly escalating. Rebound acid hypersecretion, defined as an increase in gastric acid secretion above pre-treatment levels following antisecretory therapy, has been observed within two weeks after withdrawal of treatment and can lead to acid-related symptoms and possibly PPI dependency.
American Gastroenterology Association July 1, 2009
Gastroenterology July 2009; 137(1):80-7, 87
Dr. Mercola's Comments:
If you have heartburn, acid reflux, gastroesophageal reflux disease (GERD), peptic ulcer disease or any acid-related condition, chances are very high that you’ve been offered a prescription for a proton pump inhibitor (PPI)
PPIs like Prilosec, Nexium and Prevacid are among the most commonly prescribed drugs in the world, and their use for treating acid-related symptoms is increasing rapidly.
But these drugs are not only vastly overused … they’re very dangerous as well.
To start, they actually CAUSE the very type of symptoms that they’re intended to prevent if you stop taking them.
In the study above, more than 40 percent of healthy volunteers experienced heartburn, acid regurgitation and dyspepsia (pain and fullness in your abdomen) in the weeks after stopping the drugs. These were symptoms they did NOT have before!
It appears the drugs lead to “rebound acid hypersecretion,” which is an increase in gastric acid secretion above pre-treatment levels within two weeks of stopping the drugs.
Essentially, because these drugs slam the brakes on the acid-producing pumps in your stomach, when you stop taking them that built-up acid can be unleashed with a vengeance.
Meanwhile, studies show that up to 33 percent of people taking PPIs continue to refill their prescriptions without an apparent need for them. Could it be that many of these people continue to refill their prescriptions because they have severe withdrawal symptoms each time they run out … and are assuming they need MORE of the drug to help them?
This is a vicious cycle -- one that can easily lead to tolerance and dependency on these drugs. As the researchers of the above study astutely point out:
“If rebound acid hypersecretion induces acid-related symptoms, this might lead to PPI dependency. Our results justify the speculation that PPI dependency could be one of the explanations for the rapidly and continuously increasing use of PPIs.”
Acid-Reducing Drugs are the Opposite of What Most People With Acid Reflux Need
As Dr. Jonathan Wright explained in detail in an interview I did with him last year (if you’re a member of my Inner Circle, you may have received it already), heartburn and GERD are almost always caused by a LACK of stomach acid, rather than an overproduction thereof.
Further, acid reflux (of which heartburn is the primary symptom) is commonly related to hiatal hernia -- a condition in which the acid is coming out of your stomach, where it’s supposed to remain.
After food passes through your esophagus into your stomach, a muscular valve called the lower esophageal sphincter (LES) closes, preventing food or acid to move back up. Gastroesophageal reflux occurs when the LES relaxes inappropriately, allowing acid from your stomach to flow (reflux) backward into your esophagus.
An organism called helicobacter pylori (initially called campylobacter) can also cause a chronic low-level inflammation of your stomach lining, and is responsible, or at least a major factor, for producing many of the symptoms of acid reflux.
There are actually over 16,000 articles supporting the fact that suppressing stomach acid does not treat the problem. It only treats the symptoms. And one of the explanations for this is that when you suppress the amount of acid in your stomach, you decrease your body’s ability to kill the helicobacter bacteria. So it actually makes your condition worse and perpetuates the problem.
More Reasons Why Reducing Your Stomach Acid is a Risky Bet
When you take PPIs, which significantly reduce the amount of acid in your stomach, it impairs your ability to properly digest food.
Reduction of acid in your stomach also diminishes your primary defense mechanism for food-borne infections, thereby increasing your risk of food poisoning.
Additionally, if you fail to digest and absorb your food properly, you will not only increase your risk of stomach atrophy but also nearly every other chronic degenerative disease.
These drugs have also been linked to an increased risk of pneumonia, and result in an elevated risk of bone loss. The risk of a bone fracture has been estimated to be over 40 percent higher in patients who use these drugs long-term.
If You’re Already Taking These Drugs, Avoid Stopping Cold Turkey
You should NEVER stop taking proton pump inhibitors cold turkey. You have to wean yourself off them gradually or else you’ll experience a severe rebound of your symptoms, and the problem may end up being worse than before you started taking the medication.
Ideally, you’ll want to get a lower dose than you’re on now, and then gradually decrease your dose. Once you get down to the lowest dose of the proton pump inhibitor, you can start substituting with an over-the-counter H2 blocker like Tagamet, Cimetidine, Zantac, or Raniditine. Then gradually wean off the H2 blocker over the next several weeks.
Posted by: Dr. Mercola
September 05 2009
Acid Reflux video