Dr. Leslie Hendeles began lobbying the Food and Drug Administration to reject a decongestant in cold medicine when he had a mop of red curls and Bill Clinton had just become president.
As resistance to the drug grew, Dr. Hendeles appeared as an expert at the age of 80 to testify before the authority’s advisors, with white hair and an overview of the ingredient from 50 years ago.
His advocacy culminated in the advisory panel’s unanimous vote Tuesday concluding that the decongestant, a common ingredient in cold and flu medications, was ineffective.
Prompted by the news, consumers opened their medicine cabinets when they learned that the decongestant phenylephrine was listed in more than 250 of their favorite congestion medications, including some versions of DayQuil, Sudafed, Tylenol and Theraflu. And the decision has caused some confusion — experts say the ingredient in nasal sprays still works, just not when taken orally in pill or liquid form.
According to experts, since the drug is considered safe, there is no need to throw away the products that contain other effective ingredients.
Nothing will change immediately. FDA officials will have to review the panel’s decision, seek public comments and will most likely give drugmakers some time to adjust or swap ingredients rather than be faced with the decision to pull so many staples from shelves. Further delays could occur if the companies challenge the lawsuits in court. And some experts, especially Dr. Scott Gottlieb, a former FDA commissioner, have long claimed that phenylephrine actually works to some extent. Some proponents of the drug may try to resist any move that would ban the decongestant altogether.
But how phenylephrine stayed on the market for so long despite decades of study and questions is a tangled story that traces old drug standards dating back to a law signed by President Kennedy to the proliferation of meth labs using everyday cold remedies in the 1990s and even affects the pandemic.
Like other federal agencies, the FDA can move slowly, sometimes hampered by outdated rules and a mess of regulatory processes.
“There is no question that regulation of over-the-counter medications has been broken for many years,” said Dr. Joshua Sharfstein, a former agency official and associate dean of the Bloomberg School of Public Health at Johns Hopkins. The latest moves, he said, indicate that “the agency is only now taking off its handcuffs.”
One could argue that the process of breaking down phenylephrine—a drug used to dilate eyes and calm hemorrhoids—took about six decades. The Kennedy era had introduced a new law that required the FDA to evaluate a drug’s effectiveness in addition to existing safety standards.
It wasn’t until 1976 that the FDA began reviewing over-the-counter cold medications like phenylephrine as a drug class.
But by the early 1990s, the decongestant had not yet received full approval, and the long delays caught the attention of Dr. Hendeles and a group of pharmacy professors at the University of Florida.
They would become the only constant in the history of phenylephrine over the last 30 years in putting pressure on the FDA to take action.
Dr. Hendeles published his first criticism of the drug in 1993, noting that the agency was monitoring two other popular decongestants that were effective and a third that was not: phenylephrine. The medication was intended to narrow blood vessels and eliminate nasal congestion. But it was destroyed in the stomach, he wrote in a medical journal. This meant that most drugs didn’t reach the bloodstream – let alone the nose.
In the 2000s, a seemingly unrelated problem grew: Illegal methamphetamine labs in rural areas on the West Coast exploded, as did abuse of the illegal drug.
The meth cooks’ ingredient of choice was one of the most common decongestants on the market at the time, pseudoephedrine, which was available at every drugstore.
At the time, it was one of two decongestants available to relieve congestion; A third were removed in 2000 after studies revealed a link to strokes.
The meth crisis led to the passage of state and federal laws restricting the sale of pseudoephedrine-containing products, requiring consumers to show identification and sign an account to purchase them behind the counter or in a locked cabinet at a pharmacy.
Fearful of lost sales, companies with drugs containing the popular meth additive turned to the last FDA-approved option: phenylephrine.
Dr. Hendeles said he was dismayed when he saw the ingredient in medications on pharmacy shelves because he knew patients were complaining that the substitute didn’t help them at all.
He teamed up with a colleague, Dr. Randall Hatton, together, and they dug deeper, examining the data used for the drug’s initial approval in the 1970s.
Dr. Hatton discovered memos to the FDA from the 1960s and 1970s that had not been peer-reviewed. He and his colleagues analyzed the data in modern analysis software and concluded that the drug was no better than a placebo.
As her research progressed, Dr. Hendeles to reach the FDA, where he had once been a visiting scientist. He didn’t break through, he said. So he turned to the office of U.S. Rep. Henry Waxman, an evangelical California lawmaker, for help.
Mr. Waxman sent four letters citing the professors’ findings and calling on the agency to take action. “The FDA has a duty to equip Americans with the information they need so they don’t waste their hard-earned money on drugs that don’t work,” he wrote in a 2006 letter.
The FDA responded that same year, reiterating the results of its 1976 decision. The letter noted that if a consumer did not experience relief from phenylephrine, they “have the option not to purchase it.”
Dr. Hendeles, the letter says, is free to submit a petition to the agency.
And he did it. Dr. Hendeles called for a dosage review and investigation into the use of the drug in children. This led to an FDA public hearing in 2007. There, the Consumer Healthcare Products Association, the trade group that represents over-the-counter drug makers, claimed the drug worked.
Dr. Hendeles recalled a statement that he thought was eye-catching. Representatives of Schering Plow, then the maker of Claritin-D, which contained the restricted decongestant pseudoephedrine, told consultants that they had studied its rival phenylephrine and found it had no effect. The company’s newspaper advertisements touted the “bold move” to maintain the “powerful formula” for Claritin-D, according to a letter from Mr. Waxman.
Still, the advisory committee voted 11-1 that “evidence suggests” that phenylephrine “may be effective” and called for more research.
Eight years passed.
Then Dr. Hendeles and colleagues relied on a study that came from Merck, which had acquired Schering Plow. The company tested the drug at the approved dose and at a dose four times higher and again found that it did not relieve symptoms. Merck also funded a study of a slow-release formula.
But that persistent headache—congestion—didn’t go away.
(In 2014, Merck sold Claritin-D, which still contains pseudoephedrine, to Bayer.)
The Florida pharmacists petitioned the agency for a ban, using the latest study as ammunition. But their efforts were stymied by what many former agency officials described as a beleaguered over-the-counter pharmacist division, which had 31 employees in 2018.
Employees had to follow “an arcane process that handcuffed the agency and did not provide enough resources to clear a backlog,” Dr. Peter Lurie, who was the agency’s deputy commissioner until 2017.
The Florida team encountered other hurdles over the years.
After this week’s vote in posts on X, formerly known as Twitter, referred to Dr. Gottlieb, who was the agency’s commissioner from 2017 to early 2019, called the panel’s decision “a disgrace.” 06. Now there may be no good, cheap and accessible options for consumers to get gradual relief.”
In an interview on Friday, Dr. Gottlieb said he believes further research into the ingredient is needed. “I think it’s premature to say it’s not working,” he said.
Interest in the decongestant revived after pandemic legislation expanded agency staffing and overhauled FDA procedures for over-the-counter drugs to better align decisions with those of the Prescription Drug Division.
Shortly thereafter, the FDA team addressed long-standing problems with the decongestant and prepared a thorough, 89-page review of phenylephrine, which the advisory panel reviewed as the basis for its decision. (The agency’s report confirmed the findings of Dr. Hendeles and his colleagues and also found apparent biases in some data from the 1970s that led to the drug’s initial acceptance.)
“It was a joy to read,” said Dr. Hendeles.
When he testified before the panel earlier this week, Dr. Hendeles on a 1971 study that used modified diving masks to measure nasal congestion – the first to find that phenylephrine was a dud.
Other organizations, including Public Citizen, the American College of Clinical Pharmacy and the National Center for Health Research, also called on the panel to eliminate the ingredient. The industry group argued that the ingredient was effective and that low blood levels did not negate its effectiveness. A statement from Kenvue, a spinoff of Johnson & Johnson, said products containing phenylephrine make up a small portion of its business and the company sells cold products without phenylephrine.
When the agency’s advisers voted 16-0, Dr. Hendeles is enthusiastic. “Nothing was as thrilling and exhilarating as the vote,” he said.
Lawyers representing people who bought cold and flu medicines containing phenylephrine are already announcing lawsuits against the drugmakers, claiming the companies knew the decongestant was useless.
The products will remain on the shelves for the time being. “We feel vindicated for something we have worked on for a long time,” said Dr. Hatton. “But it’s not over yet.”