In 2006, the federal government mandated that cold medicines containing the effective decongestant pseudoephedrine could only be sold behind pharmacy counters, citing concerns that customers were using it to make meth. To get around this problem, popular brands like Sudafed and Benadryl promoted their decongestants with a different central ingredient: phenylephrine, which had long been FDA-approved, and which could safely appear on pharmacy shelves. Last year, products that included phenylephrine accounted for $1.8 billion in sales. There was just one problem: It didn’t work, at least not in pill form. Last week, an FDA advisory panel voted unanimously that oral phenylephrine is ineffective for decongestion, a move that may result in a number of popular products being pulled from pharmacy shelves. That it took so long for a placebo-esque ingredient to receive proper scrutiny — despite ample evidence over the years that it was less than potent — is jarring. It also raises questions about what else the FDA might be missing. To get more information about possible drugstore duds, I spoke with Aaron Kesselheim, a professor of medicine at Harvard Medical School and a faculty member in the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital.
A lot of people learned over the last couple of weeks — and many others already knew — that phenylephrine does not actually work for congestion. I was discussing this with a doctor friend of mine, and he said that regarding over-the-counter medications, there are maybe a handful that are effective and the rest are useless. Do you agree with that?
The first thing is that it’s oral phenylephrine that doesn’t work. That’s the issue. If there’s a phenylephrine preparation that is administered directly to the nasal passages, that still works.
It is true that there are hundreds or thousands of nutritional supplements and botanicals and vitamin preparations that people can buy over the counter, and there’s no evidence that they work. Some of them may even be harmful. Some of them also may be adulterated with other products. The nutritional supplement and over-the-counter vitamin-preparation market is completely unregulated, because the DSHEA Act of 1994 explicitly excluded the FDA from being able to require testing of them. However, a lot of over-the-counter drugs are very effective. A lot of them used to be prescription drugs and became over-the-counter after we got enough experience with them to be comfortable with having patients self-medicate. So drugs that you may not expect — naproxen (Aleve) or Motrin or loratadine (Claritin) or Prilosec, all those drugs used to be brand name and were converted to over-the-counter.
There are also products out there — remnant products from the pre-1962 era like phenylephrine — where the level of evidence behind them isn’t very strong. There was a period of time between 1938 and 1962, where in order to get on the market, all you had to do was show that you weren’t killing people.
That’s quite a low bar.
Yeah. Then in 1962, the requirement was added that you have to demonstrate efficacy. And so at that point, the FDA started the process of going back and looking at all the drugs that had come on the market in the prior 25 years, and created a monograph system for these over-the-counter drugs.
It said, “Look, there are tens of thousands of these drugs. We can’t look at them each individually, so we’re going to create these buckets of products.” That’s when it re-reviewed phenylephrine and the data that were submitted to it were passable, I guess. And they allowed it to go forward, even though it seems like the data that was submitted back then weren’t as rigorous as we might like it to be. But there aren’t a lot of over-the-counter products that have been grandfathered in. The much larger market is the one for nutritional supplements.
Would you say that beyond the supplements, most products in an average drugstore are kosher?
There are the homeopathic products — those absolutely don’t work. But the FDA allows them to be sold with marketing that says that they’re useful for treating certain conditions — at least for minor self-limited conditions — even though there’s no evidence.
What’s an example of that?
There’s Silicium, there’s zinc preparation. Anything that’s labeled as homeopathic.
Why do you think the FDA allows that sort of thing?
The FDA has come to the conclusion that there’s not a safety issue for these products, and so just has generally sort of deprioritized them and said, “We don’t consider this to be a high priority.”
But the standard, the classics — the aspirins of the world, they’re all still rock solid, I hope?
Those work. They work for the purposes that they’re useful for, like aspirin works to lower your temperature, and as a preventative for certain people with high-risk disease. And ibuprofen works as a non-steroidal anti-inflammatory medication. And Prilosec works and loratadine works and Benadryl works. All of these products work for their purposes.
Why did it take the FDA so long to act on phenylephrine in your view, given the fact that people knew about it in the profession and even not in the profession, for so long?
I think it’s a combination of things. The amount of resources and in-person time that the FDA devotes to over-the-counter drugs is smaller than it devotes to prescription drugs. So there’s a resources issue, and I think it is also the case that there isn’t necessarily a concern about a safety issue here. And as a result, the urgency for the regulatory system to act on it is reduced a little bit.
I think that the fact that there isn’t a glaring safety concern also contributes to the relatively slow pace of dealing with this issue. But it’s also the case that the system the FDA has created for over-the-counter products — that monograph system where drugs are included in buckets — leads to some inertia around these products, because changing their status requires a lengthy administrative process, and the FDA’s got a lot on its plate and it’s got to prioritize things to do. I think the last time this came up as an active issue was back in the early 2000s, and they reviewed the data then and made a decision then that they didn’t think it was necessary to go through the process. And since then, there has been more data generated, and now it’s gotten back up to the top of the queue again to take a look at.
Do you sense that the FDA is getting speedier or adopting more strict scrutiny over this stuff?
No, I don’t think so.
What about further regulation of the supplements? Is there any movement toward oversight on that?
No, I don’t think there is. The reason DSHEA was passed is because the supplement industry activated its people in Washington, and I certainly haven’t heard anything about trying to walk that bill back. There was a bill last year that would require registering the supplements, but nothing about testing them ahead of time and to make sure they work.
If the FDA takes phenylephrine off shelves altogether, will effective congestion medication be a behind-the-counter thing permanently?
Yeah, it might be. I mean, people have other options. They have the nasal spray formulations. Again, we’ll see if the FDA decides to act and try to pull it off the market. If it does, it’s a long process. Especially since there’s not an urgent safety issue.
But at this point, the cat’s out of the bag on its effectiveness, because this has gotten a huge amount of publicity.
Yeah, that’s true.
This interview has been edited for length and clarity.
