FDA Suggests Removing Nonprescription Decongestant from Market

The FDA has proposed that nonprescription drugs that contain phenylephrine be removed from pharmacy shelves. Phenylephrine is nasal decongestant used in nonprescription cold products, such as Mucinex and Sudafed and other products, that the regulatory agency says is not effective.

“Based on our review of available data, and consistent with the advice of the advisory committee, we are taking this next step in the process to propose removing oral phenylephrine because it is not effective as a nasal decongestant,” Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research (CDER), said in a news release.

The agency conducted a review of all available data on the safety and efficacy of oral phenylephrine, including the historical data that were used to support the determination made 30 years ago that oral phenylephrine was effective.

The use of phenylephrine in nonprescription cold medications has become since 2006, when sales of any products pseudoephedrine were placed behind the pharmacy counter. Pseudoephedrine can be used to make methamphetamine. Congress, as an amendment to the Patriot Act, the Combat Methamphetamine Epidemic Act, began requiring photo identification and a log of sales of pseudoephedrine-containing products.

In response, many manufactures of cold products reformulated their products with phenylephrine instead of phenylpropanolamine, ephedrine, and pseudoephedrine.

But research over many years has questioned the effectiveness of phenylephrine as a nasal decongestant. In fact, an article published in 1993 on research done in the 1970 suggested that phenylpropanolamine and pseudoephedrine were effective decongestants but that oral phenylephrine was not. (Phenylpropanolamine is no longer available because it was found to be associate with strokes.)

More recently, in a review last year published in Cureus, researchers found that oral phenylephrine was not significantly more effective than a placebo in alleviating nasal congestion in adults. Researchers conducted a systematic review involving searches on PubMed, Cochrane, and Scopus databases and identified four articles that compared oral phenylephrine with placebo or standard care and their effect on congestion and nasal airway resistance.

Randy C. Hatton, Pharm.D.

Two pharmacists, Randy C. Hatton, Pharm.D., and Leslie Hendeles, Pharm.D., both from the College of Pharmacy at the University of Florida, began their research of phenylephrine in 2005 and eventually filed two petitions with the FDA for a review of the evidence and additional studies. Their efforts led the FDA to convene two advisory committee meetings, the most recent being in October 2023. All 16 members of the committee voted no on the question of whether the data support that orally administered phenylephrine is effective as a nasal decongestant.

In an article published last year in Scientific American, Hatton pointed out that phenylephrine was first approved before 1962 and later available for over-the-counter use in 1976. The modern FDA was created by the 1962 Kefauver-Harris Amendments, which created the structure for well-controlled clinical trials in people with a focus on safety and efficacy. Prior to this, manufacturers did not have to prove a new drug was effective, and chemistry studies were enough to show safety.

“But what about the drugs that were approved before 1962? This window has become a loophole that some OTC drugs fall through,” Hatton wrote in the Scientific American article. “For nonprescription drugs, 10 years after the 1962 amendment to the Food, Drug and Cosmetic Act, the FDA established the OTC monograph process, which required products that hadn't been proved effective to be reconsidered.”

For now, the FDA says product that contain phenylephrine are still available. But the agency is seeking comment on the proposed order through May 7, 2025, and will then issue a final order on phenylephrine.