Phenylephrine No Better Than Placebo

FDA advisory panel’s declaration paves way for removal of dozens of medicines in the U.S.

Your favorite cold medicine for a stuffy nose may soon be unavailable.

The FDA panel’s unanimous vote clears the way for the agency to remove oral phenylephrine from its list of approved over-the-counter ingredients. That would mean that products containing the ingredient couldn’t be sold in the U.S.

The FDA doesn’t have to follow the recommendations of its advisory panels, but it often does.

Over-the-counter products that treat cough, sinus and flu symptoms, including phenylephrine pills, generated about $5 billion in sales in 2021, according to the research firm IRI.

The Wall Street Journal reported last year that some recent studies found oral phenylephrine in certain medicines was ineffective at relieving nasal congestion from a cold, flu or allergies.

The FDA said in an analysis before the panel’s meeting that the oral phenylephrine formulations are safe but ineffective at standard or even higher doses.

The agency said that three large recent industry-funded studies evaluating medicines with phenylephrine by manufacturers found that people who took medicines with phenylephrine fared no better than those who received a placebo. The agency also found that research from decades ago didn’t meet current clinical trial design standards and included inconsistent results.

The Consumer Healthcare Products Association, an industry trade group, said at the hearing that people rely on the medicines and they should remain on the market, stating that the older research shows it is effective. “The bottom line is that oral phenylephrine is safe and that it works,” said Marcia Howard, CHPA’s vice president of regulatory and science affairs.

If the FDA found phenylephrine ineffective, manufacturers could potentially reformulate their products or submit applications as new drugs, depending on the data supporting whether phenylephrine works in the product, a CHPA spokesman said.

Physicians and pharmacists say that because oral phenylephrine is metabolized in the gut and liver, it can’t reach the bloodstream in sufficient levels and cause the blood vessels to narrow and provide relief.

“The fact that some patients think they are getting relief from specifically oral phenylephrine can be a placebo effect,” said panel member Dr. Mark Dykewicz, an allergy and immunology professor at Saint Louis University School of Medicine in St. Louis, Mo.

Some panel members also said no further study of phenylephrine is needed.

, which sells Tylenol and Benadryl, didn’t immediately respond to requests for comment. The company’s Sudafed PE also contains phenylephrine.

, which makes Mucinex, didn’t immediately respond to requests for comment.

Instead of taking pills that contain phenylephrine to clear congestion, people can take pills containing pseudoephedrine, antihistamines, or nasal spray products, including those with phenylephrine, which physicians say are effective.

s it happens, there is a near-miraculous generic cold medicine, ambroxol, that is available over the counter all over the world, but not in the United States. I stumbled on this medication last year when I was in France and had a bad cold. I went to the local pharmacy and asked if they carried something like Mucinex or Robitussin.

“We have something much better,” the pharmacist said. As I wrote last December in the Prospect, ambroxol works on an entirely different biochemical principle, to thin sputum and facilitate productive coughing, and also operates as a pain reliever and gentle decongestant with no rebound effect. My wife and I experienced it as a miracle drug for coughs and colds. A box cost eight euros.

Why is ambroxol not available in the U.S.? A comprehensive 2020 review in the journal Multidisciplinary Respiratory Medicine, available on the NIH PubMed site, found it safe and effective.

But no drugmaker has ever sought FDA approval, a time-consuming process requiring three stages of clinical trials. Why not? Because drugmakers could not make enough money with a generic to justify the expense. It’s obviously crazy to require this laborious review process for a generic that has been widely used in Europe since 1978, but this is how our system works.

Here is where President Biden could come to the rescue of cold-sufferers. He could direct the FDA to fast-track the approval of ambroxol for sale in the U.S.

When the U.S. ran short of infant formula in 2022 due to the misfeasance of a highly concentrated and profit-gouging industry, Biden ordered agencies to cut red tape and increase imports of formula from several countries, and we relied on their regulators to certify that these products were safe.

In fact, we already rely on EU agencies to certify that exported foods in general are safe and without toxic residues. European regulators are trusted with many other reciprocal delegations of regulatory authority, such as pollution standards in cars.

The European Medicines Agency, the counterpart of the FDA, has an excellent record. Under a new fast-track process, it would take just a few days for the FDA to review EMA records on the history of ambroxol in Europe to confirm that it has been safe and effective for decades.

Biden could also direct the FDA to establish a new process to fast-track approval in general for other generic drugs approved for sale in Europe but not in the U.S. That would save consumers money and give us access to beneficial medicines that we are now denied because of the manipulative greed of Big Pharma combined with an antiquated and captured FDA.

Al Gore was hailed as the man who helped bring us the internet. Joe Biden could go him one better. He could bring Americans relief from the common cold.