Nearly two decades ago, several pharmacists started calling into the University of Florida Drug Information and Pharmacy Resource Center hotline with the same query: Does phenylephrine, a common ingredient in cold medicine sold over the counter, actually work?
One of us, Dr. Randy Hatton, oversaw the call center, which was meant to train pharmacy students on how to respond to questions from health care professionals across the state. It was odd, Dr. Hatton thought, that so many providers in Florida believed the popular decongestant — found in Sudafed PE, some formulations of NyQuil and many other cold and flu treatments — wasn’t working as advertised.
After searching the literature, he came across a paper published more than a decade earlier by Leslie Hendeles, the other co-author of this essay, also at the University of Florida, suggesting that oral phenylephrine was ineffective.
Our offices were just a short walk apart, and after meeting to discuss our suspicions, we began what has so far been a nearly 20-year collaboration to determine if phenylephrine was effective at the dosage available to consumers over the counter, and later, when we discovered it wasn’t, to petition the Food and Drug Administration to remove it from shelves. This included a Freedom of Information Act request for unpublished data on the drug and multiple studies that confirmed our skepticism.
Recently, an advisory committee for the F.D.A. unanimously confirmed our findings. The agency must now decide whether products containing the ingredient should be removed from shelves and drug makers should use new formulations. Right now, phenylephrine is in hundreds of products, and Americans spent about $1.8 billion on those remedies last year.
How can an ineffective drug discovered nearly 100 years ago and marketed since the 1930s still be on the market, despite decades of drug experts like us prodding the F.D.A. to do something? It boggles the mind, and worse than that, this is only the tip of the iceberg. This decongestant is like many drugs on the market that don’t really provide relief.
Just ask your local pharmacist about over-the-counter drugs he or she suspects don’t work. It’s an open secret among many of us who study pharmaceuticals that several ingredients, including ones found in common treatments like Robitussin, Mucinex and certain cough syrups, likely don’t work as advertised. Some of these ingredients claim to help people cough up mucus, cough less or help with asthma symptoms, but studies suggest they don’t work at the current F.D.A.-approved doses.
While there have been legislative efforts to improve the regulation of ineffective drugs on store shelves, much of the process still moves too slowly and has not gone far enough.
In 1938, Congress passed the Federal Food, Drug and Cosmetic Act, which required that the federal government determine a drug is safe before it could be sold to Americans. More than two decades later, in 1962, breakthrough legislation — the Kefauver-Harris Drug Amendments — required that prescription and over-the-counter drugs must prove to be both safe and effective. As you might imagine, thousands of over-the-counter drugs were on the market before 1962. So the F.D.A. developed a system to review these drugs to make sure they worked, known as the O.T.C. monograph system.
The F.D.A. has generally relied on a risk-based approach, which prioritizes determining whether a drug is safe over how well it works. This has led to drug removals in the past. Another decongestant called phenylpropanolamine was removed from the market in the 2000s when it was shown to increase the risk of strokes when taken in high doses in over-the-counter weight loss drugs, for example.
But these investigations and removals are not happening quickly. One major issue is that many of these drugs were first evaluated with data that doesn’t meet today’s standards. Though we first petitioned the F.D.A. to look into phenylephrine more than 15 years ago, it wasn’t until company-funded studies from Schering-Plough, later acquired by Merck, reported that oral phenylephrine was ineffective that we had definitive evidence. The companies deserve credit for publishing the negative results in peer-reviewed journals. But generally speaking, the pharmaceutical industry has no incentive to fund studies proving old ingredients are effective when sales bring in billions of dollars. Schering-Plough/Merck only did its studies to evaluate the effectiveness of a higher dose of phenylephrine, and the potential to develop an extended-release product.
This is a problem for the F.D.A. because the agency doesn’t have the resources to do the enormous work of studying, evaluating and removing old and ineffective drugs, despite having the mandate to do so. There have been recent attempts to make this better: The Coronavirus Aid, Relief and Economic Security, or CARES, Act of 2020 included the first major overhaul to the O.T.C. monograph process and provided the F.D.A. with more resources, including personnel. But so much more funding is needed.
We need to get through the thicket of old drugs faster. Americans are wasting money on decongestant drugs that may not work. Even more is spent on other over-the-counter medications that are questionable, especially for coughs and colds. Dosages of many of these drugs for children are based on arbitrary age ranges without specific studies to confirm they work and are safe for different age groups. All of this doesn’t even include dietary supplements and homeopathic remedies that don’t require evidence of effectiveness or undergo any F.D.A. review.
Congress needs to develop a way of better funding the F.D.A. review process. Perhaps a small excise tax could be levied on over-the-counter sales or fees assessed to makers of over-the-counter drugs to fund the F.D.A. review process or to fund studies into drugs that went on the market before 1962. Leaders need to suggest more options. There should also be a way to prioritize which drugs to look at first. The agency should review old drugs for which there are already many complaints about lack of effectiveness in the manner it did recently for phenylephrine.
Right now, Americans spend billions on drugs that contain ingredients that will not help them. That’s not just a waste of money — it could mean they are delaying appropriate treatment, which can lead to more severe illnesses. This is risky not only for health but also for trust. The American public deserves medicines that do what they are advertised to do. And Americans should demand that from their leaders.
Randy C. Hatton is a professor at the University of Florida’s College of Pharmacy. Leslie Hendeles is a professor emeritus at the University of Florida College of Pharmacy and a courtesy professor of pediatrics at the College of Medicine. This article originally appeared in The New York Times.
