What drug did the FDA say was ineffective?: The Case of Oral Phenylephrine

October 6, 2025 •

5 min read

In September 2023, a U.S. Food and Drug Administration (FDA) advisory committee unanimously declared oral phenylephrine, a common active ingredient in over-the-counter decongestants, ineffective. This decision, which has led the FDA to propose removing the ingredient's market status, reveals a decades-old issue with a drug many consumers assumed was working. The situation raises an important question: what drug did the FDA say was ineffective?

Quick Summary

The FDA, following an advisory committee's unanimous vote, has proposed removing oral phenylephrine from over-the-counter nasal decongestants due to its ineffectiveness. The decision stems from new data showing the oral form is metabolized too quickly to work, a conclusion that overturns decades-old assumptions based on flawed evidence. This action highlights the importance of re-evaluating long-standing medication efficacy and informs consumers about more effective alternatives.

Key Points

FDA deemed oral phenylephrine ineffective: In 2023, an FDA advisory committee unanimously concluded that oral phenylephrine, used in many cold and allergy medications, is ineffective as a nasal decongestant.
The drug is being removed from the market: The FDA has formally proposed to remove oral phenylephrine's over-the-counter status, leading manufacturers to reformulate or withdraw products.
Metabolism is the root cause: Oral phenylephrine's ineffectiveness is due to extensive first-pass metabolism, which prevents sufficient drug concentration from reaching the bloodstream.
Initial approval was based on outdated evidence: The original 1976 approval relied on weak, and potentially biased, studies that did not meet modern evidentiary standards.
Effective alternatives exist: Consumers can use oral pseudoephedrine (behind the counter) or topical nasal sprays containing ingredients like oxymetazoline, which are still considered effective.
This is not an isolated event: Other drugs, like Makena for preterm birth, have also been withdrawn after failing to demonstrate clinical benefit in post-approval studies.

What Happened with Oral Phenylephrine?

The revelation regarding oral phenylephrine’s ineffectiveness came after extensive re-evaluation of its data. In September 2023, the FDA's Nonprescription Drug Advisory Committee convened to review its effectiveness and, based on new scientific analysis, unanimously concluded that the oral form of the drug works no better than a placebo. Following the committee's vote, in November 2024, the FDA officially proposed an order to remove oral phenylephrine from its over-the-counter (OTC) monograph, which would effectively bar its use in new formulations.

The FDA clarified that the drug is not unsafe but is simply ineffective when taken orally as a nasal decongestant. This means that for years, millions of consumers were purchasing and using a product with no clinical benefit for relieving their nasal congestion symptoms.

The History of a Flawed Drug Approval

For many consumers, the biggest question is how an ineffective drug could have been sold for so long. The journey of oral phenylephrine to widespread use is a complex story of market forces and historical regulatory practices.

The Rise of Phenylephrine

Original Approval (1976): Phenylephrine was initially granted approval by the FDA for OTC use in 1976 based on limited studies that, at the time, suggested some effectiveness. However, it was not a dominant player in the market for decades.
The Combat Methamphetamine Epidemic Act (CMEA) of 2005: The pivotal shift occurred with the CMEA, which restricted the sale of pseudoephedrine, a highly effective decongestant, by moving it behind the pharmacy counter to limit its use in the illegal production of methamphetamine. This created a vacuum in the easily accessible decongestant market.
Market Dominance: Pharmaceutical manufacturers swiftly reformulated their products, replacing pseudoephedrine with oral phenylephrine, which could be sold freely on store shelves. The demand for an easily accessible decongestant led to phenylephrine's market dominance in hundreds of products, including popular cold and flu medicines.

The Discovery of Flaws

Patient Reports and New Research: For years, doctors and pharmacists heard anecdotal evidence from patients that phenylephrine wasn't working. This led to persistent advocacy from researchers like Dr. Leslie Hendeles and Dr. Randy Hatton at the University of Florida, who challenged the initial approval data.
Flawed Clinical Evidence: The recent FDA review confirmed that the original approval was based on flawed evidence, including unpublished and methodologically suspect studies from the 1970s.
The Metabolism Problem: The primary reason for oral phenylephrine's failure is related to how the body processes it. When ingested orally, phenylephrine undergoes extensive "first-pass metabolism" in the gut and liver, which inactivates approximately 99% of the dose before it can reach systemic circulation to act on nasal blood vessels.

The Broader Context of Ineffective Drugs and FDA Oversight

While the oral phenylephrine case is significant due to its ubiquity, it is not an isolated event. The FDA has faced challenges with other drugs found to be ineffective or unsafe after approval.

Other Notable Withdrawals

Hydroxyprogesterone Caproate (Makena): This drug, intended to prevent preterm birth, received accelerated approval in 2011. However, confirmatory studies failed to prove its clinical benefit, and the FDA faced a lengthy process to withdraw its approval, finalized in 2023.
Unapproved Drugs: The FDA has also worked to remove numerous unapproved drugs from the market over the years, including certain versions of quinine sulfate (for leg cramps) and carbinoxamine (an antihistamine), due to significant safety concerns and lack of proven efficacy.

The Accelerated Approval Pathway

Some drugs are granted accelerated approval based on surrogate endpoints rather than direct clinical benefit, particularly for serious conditions where a treatment is urgently needed. While useful for speeding access, this pathway has had mixed results. When confirmatory trials fail, the FDA can face challenges withdrawing the drug, as seen with Makena. New legislation has since aimed to streamline the withdrawal process.

Implications for Consumers and the Market

The FDA's decision has significant repercussions for both consumers and the pharmaceutical industry.

For Consumers: Patients may now question the effectiveness of other OTC products and will need to be more vigilant in identifying active ingredients that have been re-evaluated. However, the decision also means they can stop wasting money on an ineffective product and instead use therapies that are proven to work.
For Manufacturers: Companies reliant on oral phenylephrine must reformulate their products, which could cause temporary supply chain disruptions as they transition to new active ingredients or alternative product types.

List of Effective Decongestant Alternatives

Oral Pseudoephedrine: Still a highly effective oral decongestant, though it requires an ID and must be purchased behind the pharmacy counter due to its association with methamphetamine production.
Nasal Sprays: Topical decongestants like oxymetazoline (the active ingredient in products like Afrin) and phenylephrine nasal sprays are effective because they bypass the metabolism issue associated with the oral version.
Nasal Corticosteroids: Medications like fluticasone and mometasone are highly effective for relieving allergy-related nasal congestion but not typically recommended for the common cold.

Conclusion: A Reminder of Regulatory Importance

The FDA's decision regarding oral phenylephrine serves as a critical reminder of the importance of continuous post-market surveillance of drug efficacy. It demonstrates that the effectiveness of long-standing drugs can, and should, be challenged as new data and understanding emerge. For consumers, this case highlights the value of relying on scientific evidence over convenience and the importance of knowing what drug did the FDA say was ineffective. Ultimately, while inconvenient for some, this regulatory action reinforces the FDA's commitment to ensuring that the medications available to the public are not only safe but also truly effective. For more information on the FDA's proposed order, visit the official announcement.

Comparison Table of Common Decongestants


Feature	Oral Phenylephrine	Oral Pseudoephedrine	Nasal Sprays (e.g., Oxymetazoline)
Efficacy	Ineffective for nasal congestion due to first-pass metabolism	Highly effective for nasal congestion relief	Highly effective for temporary nasal congestion relief
Mechanism	Alpha-adrenergic agonist; systemically constricts blood vessels	Alpha-adrenergic agonist; systemically constricts blood vessels	Alpha-adrenergic agonist; topically constricts nasal blood vessels
Accessibility	Over-the-counter on store shelves, but pending removal	Behind the pharmacy counter with ID required	Over-the-counter on store shelves
Active Ingredient	Phenylephrine HCl	Pseudoephedrine HCl	Oxymetazoline or Phenylephrine
Side Effects	Some systemic side effects possible, though minimal due to low absorption; potential for systemic toxicity in overdose, especially in combination products	More systemic side effects possible (e.g., elevated heart rate, blood pressure, agitation)	Localized side effects (e.g., dryness, rebound congestion with prolonged use)

Lists of Ineffective Drugs

While oral phenylephrine is the most recent and prominent example of a widely used drug deemed ineffective, the FDA's history includes other instances where drugs were pulled from the market for various reasons, including ineffectiveness. Here are examples of drugs that have faced removal or significant restrictions:

Hydroxyprogesterone Caproate (Makena): Initially approved via the accelerated pathway, it was withdrawn after confirmatory studies failed to show clinical benefit for preventing preterm birth.
Unapproved Quinine Sulfate: This drug was approved for malaria but illegally marketed for leg cramps. The FDA took action to remove the unapproved versions due to serious adverse event reports, including deaths.
Single-ingredient oral colchicine products: Following numerous adverse event reports, revised safety information and lower dosing were enforced based on new clinical trial data.
Carbinoxamine: Unapproved versions of this antihistamine were removed after serious adverse events, including infant deaths.

These examples show that drug efficacy and safety are subject to ongoing review and can be updated as new evidence becomes available.

Frequently Asked Questions

The FDA, following an advisory committee's recommendation, has determined that oral phenylephrine is ineffective as a nasal decongestant.

Scientific review found that when taken orally, phenylephrine is largely metabolized in the gut and liver before it can effectively treat nasal congestion. It simply doesn't reach the target tissue in sufficient concentration.

The FDA has proposed ending the use of oral phenylephrine. While the process may take time for full implementation, some retailers have already begun to remove products. This does not affect nasal spray forms of phenylephrine, which are still considered effective.

Oral phenylephrine gained market share after a 2005 law restricted the sale of the more effective decongestant, pseudoephedrine. Many manufacturers switched to phenylephrine as an over-the-counter replacement, despite weaker evidence of efficacy.

More effective alternatives include oral pseudoephedrine (sold behind the pharmacy counter with ID) and topical nasal sprays containing oxymetazoline or phenylephrine.

Yes. While oral phenylephrine is a recent example, others include Makena (for preterm birth) and various unapproved versions of other drugs that were removed for safety and efficacy concerns.

You should check the 'Drug Facts' label on the packaging. The active ingredient will be listed as 'phenylephrine' or 'phenylephrine HCl.' If it's a pill or liquid taken by mouth, it's the ineffective oral version.