The Impending Shift in Over-the-Counter Medications

The FDA’s proposal, now open for public comment, targets oral phenylephrine, an ingredient found in hundreds of over-the-counter oral decongestants. If finalized, this ruling would dramatically alter the landscape of the cold and flu aisle. The market share for these medications was valued at approximately $1.76 billion in 2022.

Popular products potentially affected by this order include Advil Sinus Congestion & Pain, Sudafed PE Nasal Decongestant, Vicks DayQuil and NyQuil, and Tylenol cold & Flu Severe. The core issue? Evidence suggests that oral phenylephrine is simply not effective.

A Placebo Effect? FDA’s Advisory body Weighs In

The proposed order follows a unanimous conclusion by an autonomous advisory body for the FDA. Their assessment: oral phenylephrine, while safe, is “no better than a placebo” at relieving nasal congestion. This conclusion has prompted a re-evaluation of the ingredient’s role in over-the-counter remedies.

For nearly two decades, some scientists have advocated for the removal of oral phenylephrine from the market. Despite these calls, the FDA previously maintained the drug’s availability after its last review.

It is indeed the FDA’s role to ensure that drugs are safe and effective.
Patrizia Cavazzoni, director of the administration’s Center for Drug Evaluation and Research (CDER)

cavazzoni further stated:

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, director of the administration’s Center for Drug Evaluation and research (CDER)

A Look Back: The History of Phenylephrine in Cold Medications

Phenylephrine’s journey to becoming a staple in cold and flu medications began in 1976, when the FDA initially approved it as a safe and effective decongestant. Though, this approval was based on studies, many of which were “industry-funded,” and have as faced criticism regarding their methodology.

Prior to 2006, pseudoephedrine was the primary ingredient in over-the-counter decongestants. Though, concerns arose regarding its use in the production of methamphetamine. This led to federal legislation requiring states to implement measures controlling the sale of pseudoephedrine.

Consequently, many states enacted laws requiring prescriptions for medicines containing pseudoephedrine or limiting the quantities sold from behind pharmacy counters. This regulatory shift paved the way for phenylephrine to replace pseudoephedrine in over-the-counter decongestants available in drug stores, grocery stores, and convenience stores nationwide.

Mounting Evidence of Ineffectiveness

Even as phenylephrine gained prominence, questions about its efficacy persisted. In 2005, some scientists “reviewed existing evidence” that indicated phenylephrine was ineffective at clearing nasal congestion when taken orally at the recommended dosage.

In 2007, a “citizen’s petition” urged the FDA to demand stronger proof of efficacy. Though, at the time, FDA officials called for further research, especially focusing on higher dosages.

Starting in 2015, “clinical trials” explored the impact of quadrupling the dosage of oral phenylephrine. Despite these efforts,the medicine continued to prove ineffective as a decongestant,leading to another citizen’s petition requesting the removal of these products from the market.

Years of debate culminated in the FDA committee’s analysis of three large clinical trials in 2023, which demonstrated that oral phenylephrine is “not effective at any dose.”

Studies revealed that even when ingested in higher doses, “almost no medicine reaches the nasal passages,” as it is primarily broken down in the gut.

What This Means for Consumers

It’s significant to note that the proposed order to remove phenylephrine applies specifically to oral decongestants. Nasal sprays and eye drops containing phenylephrine are not affected, as these delivery methods are considered more effective.

Despite the evidence, many consumers remain unaware of these distinctions. In 2022, “more than 242 million cold remedy products” containing phenylephrine were sold in the U.S., substantially outpacing the sales of products containing pseudoephedrine.

As the FDA’s order is currently a proposal, companies are not yet required to take action. Though, they are now on notice for potential future requirements to withdraw products containing phenylephrine as the sole active ingredient.