Heartburn and the Drug Wars
Almost half of all Americans experience heartburn or acid reflux at least once a month, and one in twenty suffers from the condition daily. What causes it?
A muscular ring or valve, the cardiac sphincter, surrounds the lower esophagus where it empties into the stomach. This ring normally prevents regurgitation or reflux of acid stomach contents into the lower esophagus. Weak sphincter tone, especially common as we grow older, combined with activity after eating, meals close to bedtime, obesity, certain foods, alcohol, or simple recumbency, can result in heartburn. The most sensible first line treatment is addressing these and other salient causes of chronic heartburn. Certain classes of drugs, especially the NSAIDs, (non-steroidal anti-inflammatory drugs) such as aspirin, ibuprofen, Tylenol (acetaminophen), Aleve (naproxen), etc. are especially important in causing advanced gastroesophageal reflux disease ("GERD"). Since these drugs are used most often by people over 65, the prevalence of reflux in this group is extremely high, often exceeding 75% of the population.
Drug treatment of heartburn, as well as peptic ulcer and dyspepsia, consists in reducing stomach acid by various means. The oldest and still the most widely used first line drugs are the antacids, such as Tums, Maalox, Mylanta, Rolaids, etc. These have the advantage of rapid relief in most patients, and low price. However, with chronic heartburn or GERD two other classes of drugs have shown great effectiveness:
- The H2-receptor antagonists, Zantac (ranitidine), Pepcid (famotidine), and Tagamet (cimetidine), etc. and
- The proton pump inhibitors, "(PPIís"), Prevacid (lansoprazole), Prilosec (omeprazole), and Nexium (esomeprazole), Protonix (pantoprazole), among others. This latter group is widely believed to be the most effective or "top" acid blockers. In actuality, however, H-2 blockers are highly effective, available over the counter and much cheaper than PPI's. Moreover, "Proton pump inhibitors are often overprescribed in long-term care, disregarding published guidelines for their use...Simple antacids and H 2 blockers are often overlooked for initial use for simple dyspeptic symptoms and uncomplicated GERD, respectively." See this page.
Ten years ago, the multinational pharmaceutical company, AstraZeneca launched what company insiders nicknamed the Shark Fin Project whose focus was the prescription drug Prilosec, the heartburn medication that, in one five-year stretch had earned the company an astounding $26 billion. The patent on the drug was due to expire in April of 2001, and the big question was what to do if those enormous profits melted away when the anticipated low-priced generics came along to compete.
The Shark Fin dream team drew up a long list of options, including changing the formulation of Prilosec to make it work faster and longer, make it a liquid, or combine it with a different heartburn remedy. In the end, AstraZeneca decided on a brilliant strategy of simple chemical re-formulation. Like some chemical compounds Prilosec, is composed of two "isomers" - a left-hand (l-form) and a right-hand (d-form) or 3-D version of the same molecule. In some cases, removing one of the isomers can reduce side effects, reduce or enhance the effectiveness of the drug. In all cases, the Patent Office recognizes each isomer, as a unique chemical, and a compound with one isomer as a separate invention from one with both. So AstraZeneca cut Prilosec in half, making a single isomeric form of the drug, and calling it Nexium, the now famous "purple pill." "Proving "that Nexium was more effective than Prilosec in a single two month trial on an unusual subset of patients with heartburn (erosive gastritis) with a statistically unconvincing result, was enough to convince the F.D.A. who gave their approval of the drug in March 2001. Nexium hit the pharmacy shelves priced at $120 for a month supply of pills. Today, four years later, it still retails for approximately $95 for a month supply.
To persuade physicians and patients to think of Nexium as state of the art, thus keeping cheaper generics at bay, AstraZeneca spent half a billion dollars in marketing and advertising in the year following the launch. It is now one of the half-dozen top-selling drugs in America. But even Prilosec which has now become Prilosec OTC (over the counter), and selling for $23 for a months supply, has been scarce from pharmacy shelves for over a year. This was disclosed in The New York Times (March 2, 2005), Where Has All the Prilosec Gone: How Empty Shelves Are Bolstering a Drug Makerís Bottom Line." (Procter & Gamble and its partner, AstraZeneca claim they underestimated demand for the drug and are working "to increase production and correct the shortage.")
As reported in the New Yorker, "Nexium has become a symbol of everything that is wrong with the pharmaceutical industry. The big drug companies justify the high prices they charge - and the extraordinary profits they enjoy - by arguing that the search for innovative, life-saving medicines is risky and expensive. But Nexium is little more than a repackaged version of an old medicine." The Prilosec pattern, repeated across the pharmaceutical industry, "goes a long way to explain why the nation's prescription drug bill is rising an estimated 17 % a year even as general inflation is quiescent," the Wall Street Journal concluded, in a front-page article that first revealed the Shark Fin Project.
In The Truth About the Drug Companies: How They Deceive Us and What to Do About It (Random House; $24.95), Marcia Angell, a former Editor of The New England Journal of Medicine, says the story of Nexium and drugs like it is proof that the pharmaceutical industry is "now primarily a marketing machine to sell drugs of dubious benefit."
But does the blame lie exclusively with AstraZeneca and the other pharmaceutical companies that peddle "me-too" drugs and undermine generics by clever strategies and audacious salesmanship? Since Nexium is a prescription drug, every person who takes it was given written approval to use it by a doctor. But does the physician know that the patient can get omeprazole or Prilosec, virtually the same drug at a fraction of the price, either as a prescription or, when available, over the counter? Do the medical journals who accept so much pharmaceutical advertising, always "tell it like it is"?
Perhaps doctors as professionals should know cheaper ways to treat heartburn when the patient comes in for the first time. There is rarely a need to "start at the top" with the PPIís like Aciphex, Prilosec, and especially "the purple pill," Nexium, when plain old antacids supplemented with H2 antagonists, such as Tagamet or Zantac are exceedingly effective for the vast majority of patients. If the patient fails to respond to generic Zantac, Tagamet, or Pepcid-AC at $10 a month, the doctor could always put him on the cheaper, generic form of Prilosec, omeprazole at $23 a month.
The patient's insurance companies are equally at fault when they pick up the tab for Prilosec, let alone Nexium, without first requiring a trial of an H2 blocker. Both the physician and the insurance company, meanwhile, could have sent the patient to any drugstore in America, where he or she would have found, antacids next to Pepcid, Zantac, Tagamet or their generics on the shelves. Surely there is more than one culprit in the prescription drug fiasco.
Martin F. Sturman, MD, FACP
Copyright 2005, Mathemedics, Inc.
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