The Journal. - The Two Scientists Taking Down Cold Medicines That Don't Work

Episode Date: November 1, 2023

Randy Hatton and Leslie Hendeles spent nearly two decades trying to convince the Food and Drug Administration that phenylephrine, a drug commonly used in cold medicines, was ineffective. In September, an advisory panel finally agreed. Now, some of the medicines are being pulled from store shelves.Further Reading: - If Some Cold Medicines Don’t Work, What Should You Take for a Stuffy Nose?  - CVS Pulls Certain Cold Medicines From Shelves and Will Stop Selling Them  - These Are the Two Scientists Taking Down Cold Medicines That Don’t Work  Learn more about your ad choices. Visit megaphone.fm/adchoices

I've been a little under the weather recently. Stuffy nose, sore throat. It's no fun. It's not COVID or the flu. My doctor said it's just a good old-fashioned cold. I've used a humidifier, drank warm tea, and taken cough drops. And I've been looking very closely at over-the-counter cold medicine, because recently I learned that there's an active ingredient that's been marketed for colds and allergies that,

when taken orally, just doesn't work. It's called phenylephrine. FDA advisory panel's raising some very serious questions about a key ingredient in popular cold medicines. To be honest with you, it doesn't work. Phenylephrine works no better than a placebo to unclog your stuffy nose. There are two scientists you can thank for figuring this out. Randy Hatton. I'm a clinical professor

in the Department of Pharmaceutical Outcomes and Policy at the University of Florida College of Pharmacy. And Leslie Hindelis. I am a professor emeritus in the University of Florida College of Pharmacy. Randy and Leslie spent nearly two decades questioning the effectiveness of oral phenylephrine. Did you ever see someone in line at the pharmacy

buying some of this phenylephrine and just like swat it out of their hand and be like, it doesn't work. Don't buy it. I think we have been telling people, whether it's our family member, friends, colleagues, anybody that would probably listen to us, that that was not the best option as an oral decongestant. And last month, an FDA advisory panel finally agreed with them. And last month, an FDA advisory panel finally agreed with them. Welcome to The Journal, our show about money, business, and power.

I'm Ryan Knudson. It's Wednesday, November 1st. Coming up on the show, how did a cold medicine that doesn't work stay on the market for so long? Your teen requested a ride, but this time, not from you. It's through their Uber Teen account. It's an Uber account that allows your teen to request a ride under your supervision with live trip tracking and highly rated drivers. Add your teen to your Uber account today. When was the last time either of you had a cold? It's been quite a long time for me.

I can't remember the last time I've had a cold. Yeah, I can't either. Wow, lucky you guys. Even though Randy Hatton and Leslie Hendles apparently have great immune systems, they spent a lot of time thinking about cold medicine. Their story starts in the early 2000s. Back then, a lot of over-the-counter cold medicines contained an active ingredient called pseudoephedrine. One of the most popular brands is Sudafed.

And while it works really well to clear nasal congestion, it can be a key ingredient in methamphetamine. Drug dealers were going around buying boxes of this stuff and using it to make meth. as we're going around buying boxes of this stuff and using it to make meth. So, in 2005, the federal government passed a law called the Combat Methamphetamine Act. It required pharmacies to put medicine that contained pseudoephedrine behind the counter, and customers had to show their ID in order to get it.

It made pseudoephedrine a lot harder to get. The drug-dealing character Jesse Pinkman even complained about it on the show Breaking Bad. What about pseudo, man? How are we going to get. The drug-dealing character Jesse Pinkman even complained about it on the show Breaking Bad. What about pseudo, man? How are we going to get that? You think the meth fairy's just going to bring it to us? God, it takes me a week to get this stuff. Here's Randy again.

When that occurred, the manufacturers of products that were marketed as oral nasal decongestants reformulated their products and took out the pseudoephedrine and for many of those products put in oral phenylephrine so they could keep their products in front of the counter to assure that they would maintain the sale of their products. Because it's more difficult obviously to get something from a pharmacist behind the counter than if you can just grab it off the shelf and go check out at the front.

I believe the perception is that it's more difficult. It actually is quite easy, but the perception is that it would be less accessible and that people wouldn't see it. Drug companies replaced pseudoephedrine, which worked, with a different ingredient called phenylephrine. Until then, oral phenylephrine wasn't that popular.

And importantly, phenylephrine couldn't easily be used to make meth. So companies could keep selling it wherever they wanted. Last year, according to the FDA, phenylephrine was used in about 250 products and generated $1.8 billion in sales. The reason why the companies wanted to switch to phenylephrine is because it's sold in convenience stores, in grocery stores that don't have pharmacies, in airports, on cruise ships. And so all of those sales they would have lost if they didn't find a replacement. When the law was passed in 2005, Randy was working at the University of Florida

and running a teaching laboratory for pharmacy students. The laboratory's main mission was to field questions from medical professionals, and the students would do research to help find the answers. And after more cold medicines started to contain phenylephrine, Randy's laboratory started getting calls from pharmacists about it, pharmacists who said they were hearing from patients that it didn't work. So before these products contained pseudoephedrine, so let's think of the main brand name, Sudafed. So the patient, before this happened, they would go to the pharmacy shelves,

grab Sudafed off the counter, and then they would take it home, and it would work. And then all of a sudden, now they would go to the pharmacy, and now instead of Sudafed, it would be Sudafed PE for phenylephrine. They would think it's the same thing. They would grab it, take it home, and say, this doesn't work. What they had been using before now didn't work. They didn't realize it was something different. And so that is what led to the questions. And what were the pharmacists saying? Like, did they have a hunch as to what was going on? No, they were totally stumped. You know, they were trying to figure out why it wasn't working or perhaps if they were using the wrong dose. So Randy and his students started doing research on the effectiveness of phenylephrine.

And he found a study from 1993 that showed that it was no more effective than a placebo. That study was authored by Leslie. And Leslie's office was right down the hall. Leslie is an expert in something called pharmacokinetics, meaning how drugs move through the body. And his research demonstrated that when phenylephrine is taken orally, like in a pill, it doesn't work.

Pseudoephedrine and phenylephrine, like these words sound very similar to me, but how different are these two drugs when they enter the body? Phenylephrine is extensively metabolized in the body. Pseudoephedrine is not metabolized at all. It's absorbed well, and it's excreted by the kidneys. So just minor differences in the way drug chemicals look can have big differences in how they're handled by the body. chemicals look can have big differences in how they're handled by the body. There's enzymes in the gut that inactivate phenylephrine, but they don't inactivate pseudoephedrine. So pseudoephedrine, you swallow it and 90% or more of the dose you swallow gets

into the bloodstream and the blood carries it to the nose. With phenylephrine, what we now know is that 99% of the drug gets inactivated before it even gets into the blood. We know that phenylephrine does do what it's supposed to when it's administered by other routes. For example, phenylephrine nasal spray, spraying the phenylephrine right into your nose, right onto those vessels in your nose, spraying the phenylephrine right into your nose, right onto those vessels in your nose. Very effective. Not very long-acting, but very effective. If you give it IV, so sometimes it's given IV in intensive care units or in the operating room when you're trying to raise somebody's blood pressure.

So it does stimulate the blood vessels when it's given IV or topically. Eye doctors put it in your eyes to dilate your pupils, so it's very effective for that. Commonly used today. Phenylephrine was patented back in the 1920s and was greenlit for use in over-the-counter products by the FDA in 1976. While Randy and Leslie weren't concerned about phenylephrine's safety, they didn't think it was effective. So they collected all the studies they could find about phenylephrine and did a big analysis of everything they found. They finished their review in 2007.

We got all those studies, had to take those studies and first ferret out all the information that was irrelevant, get to the studies, critically evaluate them, do what we call a systematic review, critique each one of those studies, then mathematically combine all those results and do some subset analyses to see if there were any trends. And then after all that, we were confident that the 10 milligram dose was not effective. Do you remember anything about that moment when you came to that conclusion? Did you look at each other when you got the results and say, great, Scott, we've got him? I didn't because I didn't think it was effective back in 93. So, you know, what this did was the icing on the cake.

Well, I mean, if you think about it, the very well done study that Leslie talked about that he used in 1993 was very suggestive that it did not work. The fact that we were getting these anecdotal calls from pharmacists that patients were saying it didn't work, we were pretty suspicious that it didn't work. But to be fair, we wanted to look at all the evidence. So when all the evidence was looked at and it validated our concerns, yeah, we felt confident enough that we should do something about it. But doing something about it would turn out to be much harder than they originally thought. That's next. TD Mortgage Direct makes it quick and easy to get the answers you need. Just answer a few questions and get personalized advice from a TD Mortgage Specialist. And you can get up to $4,100 with a new TD Mortgage.

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Only in theaters August 2nd. After Randy and Leslie showed that oral phenylephrine didn't work, in 2007, they filed a petition with the FDA, asking for a review of the effectiveness of a 10-milligram dose. There were two things that we requested. One was that they would approve a higher dose. There was some evidence to suggest to us from the meta-analysis that a 25-milligram dose might be more effective than a 10. And so we suggested that they consider raising the dose, but yet require companies to test to prove that it's safe and effective. Another big

issue for me, since I've been involved in pediatrics, is there was no data on the safety and efficacy in children. And yet the FDA had approved it down to two years of age. So you could give it to a preschool toddler without knowing whether it works or whether it was safe. And so the second item in our petition was to remove the approval for children under 12. And what was the FDA's response when you filed this? There was no response. When the agency didn't respond, Randy and Leslie went to Henry Waxman, a congressman from California who sat on a committee that had oversight over the FDA.

Waxman sent the agency multiple letters. And eventually, in late 2007, the FDA agreed to do a review. But for Randy and Leslie, it didn't go well. The FDA framed the question for the advisory committee to be very lenient for oral phenylephrine, that is there any evidence that oral phenylephrine might be effective? Not whether it wasn't really effective or was the evidence any good. And so that kind of gave an out that the advisory members could say, yes, there is evidence. It may not be very good, but there is evidence. The panel said more research was needed,

but that was all. So phenylephrine continued to be sold. How are you feeling when you're still seeing this ineffective medicine on the shelves? Were you feeling frustrated? Yeah, I think it was frustrating to know that these products are being widely used and advertised.

But Randy and Leslie didn't quit. They filed a second citizen's petition in 2015, after more studies were published showing phenylephrine's ineffectiveness. These were well-done, large, randomized, placebo-controlled trials that showed that oral phenylephrine was no different than placebo, and we felt compelled to then request again for the FDA to once again look at that. The issue started getting more attention last year after a Wall Street Journal story

raised concerns about the drug's effectiveness. Eventually, just a couple of months ago, in September, an FDA advisory panel agreed with Randy and Leslie and ruled that oral phenylephrine is, in fact, ineffective. And this decision did make a difference. Pharmacy chain CVS is going to stop selling some of its most common cough and cold medicines. The products impacted only contain phenephrine as an active ingredient. Well, I think we felt good about that decision. impacted only contain phenephrine as an active ingredient.

Well, I think we felt good about that decision. I mean, we felt vindicated for something that we've been working on for nearly 20 years, that the FDA staffers and the advisory committee voted unanimously of what we had been saying for quite a long time. So that's quite rewarding. That was exhilarating for me to hear that.

The FDA advisory panel's decision is just a recommendation, though. It doesn't actually ban phenylephrine. Randy says that process could still take years. Do you think this would have happened if you two weren't pushing this issue so hard over the years? Just the fact that it took this long is the answer to that question. I mean, quite frankly, I think that the news media coverage right now is very beneficial. I think the lay public is learning that just because it's on the shelf doesn't mean that it works. That's a big lesson for people to learn, and they need to ask their pharmacist before they pick up a product. So that's one thing.

The drug companies are learning that they're having to answer the question, why are they selling something that they know is not effective? That's all for today. Wednesday, November 1st. The Journal is a co-production of Spotify and The Wall Street Journal. Special thanks to Jared Hopkins

for his reporting in this story. Thanks for listening. See you tomorrow.