— They’ve been called “The Purple Pill” and “The Healing Purple Pill.”
— Many Americans call them lifesavers.
— But a growing number of lawsuits claim that heartburn medications like Prilosec, Nexium and Prevacid lead to long-term, serious side effects, including chronic kidney disease, which can lead to kidney failure.
— In a complaint filed in February, one Northern California woman, who we’ll refer to as Penny, says she “suffered kidney failure requiring a transplant due to proton pump inhibitor use, including substantially Prilosec.” Proton pump inhibitor, or PPI, is the medical community’s name for this category of heartburn drug.
— Penny asked ABC10 not to use her full legal name for privacy reasons, though she understands that her lawsuit is publicly available.
— “I remember him saying it, and then it being repeated after – don’t miss a dose. Now that I look back, I wish I had missed a dose,” Penny said, referring to her prescription for Prilosec.
— Penny found Prilosec to be hugely helpful in helping her maintain her acid reflux, so she stayed on the drug for more than a decade.
— “The only thing I remember is him saying, ‘How are you doing?’ And I remember telling him that the Prilosec really works,” Penny said.
— Then, Penny went in to see her doctor for what she thought was a minor eye infection. Her eyes, however, were simply a window to her kidneys. Her doctor ordered a urine analysis and found out quickly that Penny’s kidney function had been reduced to 30 percent.
— Within a year, Penny’s kidney function had fallen so low that her doctor told her she would need a transplant.
— History of proton pump inhibitors
— Over the past thirty years, the market has been introduced to a number of PPIs, and usage quickly became widespread.
— The Food and Drug Administration (FDA) approved the first on the market, prescription Prilosec, in 1989.
— Prevacid, the offering from Takeda Pharmaceuticals, got approval six years later.
— In 2001, Prilosec’s patent expired. Its maker, AstraZeneca, introduced prescription-only Nexium, a PPI with a slightly different formulation, the very same year.
— Doctors say all the drugs in this category operate in a nearly identical way, blocking acids from being pumped into the stomach.
— Then, over-the-counter versions opened up an additional market. In 2003, the FDA approved Prilosec OTC for use without a physician’s note; Prevacid 24HR came online in 2009, followed by Nexium 24HR in 2014.
— By 2013 – a year before Nexium 24HR was introduced - Consumer Reports was already citing data from information services company IMS Health showing that PPIs were one of the drug categories with the highest sales in the U.S., doing $9.5 billion in sales in 2012 alone.
— Overuse and growing research
— Doctors agree that the PPIs are extremely useful – and effective – for serious gastrointestinal diseases. They can be used to treat ulcers, as well as Barrett’s esophagus, a condition which, when left untreated, can develop into esophageal cancer.
— But the drugs are also marketed for treatment of gastroesophageal reflux disease, or GERD.
— With research showing that anywhere from 30 to 70 percent of PPI users don’t need the drugs at all, Dr. Adriane Fugh-Berman points a finger at GERD as being a driving force behind PPI overuse.
— In addition to being a medical doctor, Fugh-Berman is a professor at Georgetown University Medical Center and the director of the university’s PharmedOut project, which “advances evidence-based prescribing” and teaches physicians about pharmaceutical marketing practices.
— “GERD is what we used to call heartburn,” Fugh-Berman said, adding that the condition can be treated with lifestyle and diet changes.
— “Promotion of GERD occurred with both physicians and providers, and also with patients, as well,” Fugh-Berman said. “There were efforts to educate patients that they needed to be treated with a drug every day, even if they weren’t having symptoms every day.”
— Medical Marketing and Media published an interview with former Prilosec marketer Tom McCourt who explained just how AstraZeneca turned Prilosec into a success.
— “What we saw was that when a patient visited his doctor and started taking about heartburn, he was prescribed Zantac. The next time he went in, the doctor asked, ‘Is your heartburn better?' The patient would be like, ‘Yeah, it's better,' and that would be the end of it,” McCourt recalls. “We needed to change the question to, ‘Do you still have heartburn?' The goal had to be no heartburn.”
— Medical Marketing and Media reporter Larry Dobrow adds, “Once that subtle shift was effected, Prilosec surged.”
— Long after PPIs became a billion-dollar category, the makers of the drugs kept spending on advertising.
— Market research and data consultancy Kantar says that in 2015 and 2016, a combined total of more than $250 million was spent on advertising for over-the-counter and prescription PPIs. By this point, these drugs were far from unknown. Prilosec had been available with a doctor’s note for more than a quarter-century.
— Suffice to say, PPI usage had grown widespread.
— In 2013, more than 15 million Americans were thought to have been prescribed PPIs. That number – representing close to one in 20 Americans – doesn’t even reflect the people using the over-the-counter versions.
— Eventually, nephrologist and researcher Dr. Morgan Grams of Johns Hopkins, says she started to notice that most of her patients who had come in with chronic kidney disease had been using PPIs.
— “It was known that PPIs caused ‘acute interstitial nephritis,’ which is sort of like an allergic reaction in the kidneys,” Grams said.
— She added that because PPIs had become so common, they were actually the leading cause of the infection.
— “But before we started our research, it hadn’t been shown to have other effects like chronic kidney disease,” Grams said.
— That research, published in 2016 in the Journal of the American Medical Association, has made waves in the medical community and raised questions about the side effects of PPIs, which were previously thought by many physicians to be relatively harmless.
— The large observational study examined more than 10,000 people. Ultimately, Grams and the other researchers behind the study found that usage of PPIs were correlated with an increased risk of developing chronic kidney disease.
— “We did many, many sensitivity analyses, so the exact number depends on which sensitivity analysis, but it was usually about 20 to 50 percent higher for those using PPIs than those who were not,” Grams said.
— This type of study, being observational, does not establish causality, or show exactly how PPIs would physically lead to chronic kidney disease. Grams says causality will be hard to determine in humans, as the best step forward would be to organize a randomized control trial, in which some participants are put on PPIs for a long period of time and others are not.
— “We don’t want to do a randomized control trial to see if someone’s going to get a bad effect … So I’m not sure if subsequent studies will be able to look at this to determine a causal mechanism in humans,” Grams said.
— In 2017, Kidney International published a subsequent study looking at nearly 200,000 patients within the Veterans Affairs medical system. This research also found that patients using PPIs had a 20 percent higher risk of developing chronic kidney disease and end-stage renal disease.
— The warning signs
— In 2011, advocacy group Public Citizen sent a petition to the FDA expressing concerns over serious side effects and asking for stepped-up warnings about PPIs.
— The group asked for black-box warnings – the most serious type of warning on approved prescription drugs – alerting consumers that using PPIs could cause a rebound of acid production, which would lead to dependence on the drug.
— Public Citizen also wanted a black-box warning about fracture risk, arguing that long-term PPI usage had been associated with an increased risk of osteoporosis-related fractures.
— In addition, Public Citizen asked the FDA to add warnings on the label telling users about the possibility of developing acute interstitial nephritis.
— Three years passed.
— Public Citizen sued the FDA in federal district court for “unreasonable delay” in responding to the petition.
— Ultimately, when the agency responded later in 2014, it denied the request for all of the black-box warnings.
— The FDA did, however, change the labels of prescription PPIs to warn users of acute interstitial nephritis – but only the labels of prescription PPIs, and not the over-the-counter versions.
— In its response to Public Citizen’s petition and in other safety communications, the FDA drew a distinct line between prescription and over-the-counter PPIs because the over-the-counter drugs are only approved for a 14-day course of treatment.
— If the over-the-counter versions are only to be used for this sort period of time, the thinking goes, then consumers don’t need the additional warnings.
— The cost and the fine print
— Prescription and over-the-counter PPIs are available in the same doses, and work the same way to curb acid production.
— And once cost is factored in, it stands to reason that some users might reach for the over-the-counter drugs rather than get a prescription filled. In doing so, however, they would never see the warnings prescription PPIs have about side effects tied to long-term use, nor the warning about acute interstitial nephritis.
— Many PPI users shopping around for PPIs might have been encouraged to ditch the prescription pills for the OTC offerings. In 2013, Consumer Reports published a guide to choosing a PPI, noting that the drugs “differ a lot in price.”
— In the end, the publication ended up touting over-the-counter PPIs, noting that they cost between $19 and $24 per month, compared to prescription generic PPIs, which cost anywhere from $69 to $172 per month. Prescription brand-name PPIs were even more expensive, ranging from $170 to $375 per month.
— Josh Wilson, the attorney representing Penny, questions whether heartburn sufferers are adequately warned against taking PPIs on a consistent, ongoing basis.
— He points to commercials for Prilosec OTC. In one, comic figure Larry the Cable Guy stands in front of a barbecue grill and says, “What’s better than zero heart burn? Nothing, that’s what. That’s why I take Prilosec OTC each morning for zero heartburn.”
— “Each morning,” he says, despite the fact that the fine print onscreen says that the drug is approved only for a two-week period.
— The FDA also 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.”
— Number of lawsuits expected to grow
— Penny got lucky. In 2015, she was the recipient of a successful kidney transplant from a family friend. And while she still takes a good deal of drugs related to her new kidney, Prilosec isn’t one of them.
— Now, she manages her acid reflux with lifestyle and diet changes.
— “I think if I had any indication that it would have done damage to any of my organs, I would have done it – go off or tried to go off,” she said.
— While she’s now relatively healthy, she says she believes there won’t be change – or adequate warnings – if the makers of the drugs don’t get sued. She’s suing the pharmaceutical companies behind the drugs, rather than her doctors, because she feels that her doctors were working with the best possible information they had.
— She’s not the only one suing the drug companies.
— In a statement, AstraZeneca told ABC10 it was “confident in the safety and efficacy of NEXIUM and PRILOSEC when used in accordance with the FDA approved label, which has been established through numerous clinical trials. We will vigorously defend against the allegations made by the plaintiffs.”
— Takeda, the maker of Prevacid, wrote: “We can confirm that lawsuits have been filed by plaintiffs who allege kidney damage from using one of our products. We strongly support the safety and efficacy of all of our medicines which have been cleared for marketing in the United States by the U.S. Food & Drug Administration.”
— Due to pending litigation, Takeda’s spokesman said it couldn’t comment further.
— P&G, which distributes Prilosec OTC, wrote that it also denies the allegations and stands by the efficacy and safety of the drug.
— “As with any OTC medication, it is important to read and follow all label directions to ensure proper dosing and to avoid drug interactions. Prilosec OTC is to be used once a day, every day for 14 days as a course of treatment. Do not take for more than 14 days or more often than every 4 months unless directed by a doctor,” the company added.
— Pfizer, which markets Nexium 24HR, echoed the other pharmaceutical companies: “Pfizer believes these lawsuits are without merit. PPIs provide an important health benefit to consumers and the medicines’ FDA-approved labels have always provided accurate information on their benefits and risks. We stand behind the safety and efficacy of our medicines.”
— Aside from Penny’s case, there are more than 15 other lawsuits pending in different federal courts around the U.S. Earlier this year, lawyers for a number of plaintiffs attempted to combine their cases in what’s known as a multidistrict litigation, or MDL.
— The judge ultimately rejected the petition for the MDL, but the plaintiffs’ lawyers can attempt to combine cases again in the future.
— And in their petition, it sounds like there will be more people like Penny eager to sign on.
— The lawyers wrote that more than 5,000 possible cases of kidney damage related to PPI use are under investigation.
— They say they that the number of lawsuits will likely increase by hundreds in the coming months.