FDA Proposal to Remove Oral Phenylephrine as a Decongestant (2024)

Table of Contents

1. What the FDA Did
2. What the Proposal Would Change
3. Key Terms: OTC Monographs, GRASE and Administrative Orders
4. The Background the Documents Give: 1976 to 2023
5. Why the FDA Set Aside the Older Studies
6. The Newer Clinical Trials the FDA Reviewed
7. The Pharmacology: How Little Active Drug Reaches the Blood
8. What the FDA Found on Safety
9. What the Proposal Does Not Do
10. Other Options the FDA Lists for Nasal Congestion
11. Dates and Legal Status as of 11 October 2026
12. How It Fits the FDA’s Earlier Handling of Oral Phenylephrine
13. Primary Documents
14. Key Research Papers
15. Connections

1. What the FDA Did

The FDA news release dated 7 November 2024 is titled “FDA Proposes Ending Use of Oral Phenylephrine as OTC Monograph Nasal Decongestant Active Ingredient After Extensive Review.” It states that the agency is proposing “to remove oral phenylephrine as an active ingredient that can be used in over-the-counter (OTC) monograph drug products for the temporary relief of nasal congestion after an agency review of the available data determined that oral phenylephrine is not effective for this use.” The release adds that the proposal “is based on effectiveness concerns, not on safety concerns.”

The legal instrument is a proposed administrative order, numbered OTC000036, titled “Amending Over-the-Counter Monograph M012: Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use.” The order itself was posted in the FDA’s OTC Monographs@FDA portal. A short Federal Register notice of availability, published Friday 8 November 2024 on page 88787 of volume 89, told the public where to find it. That notice was dated 31 October 2024 and signed by the FDA’s Deputy Commissioner for Policy, Legislation, and International Affairs, and it names a contact in the Center for Drug Evaluation and Research. It says the FDA issued the order under section 505G(b)(1) of the Federal Food, Drug, and Cosmetic Act.

The release quotes the director of the FDA’s Center for Drug Evaluation and Research (CDER): “It is the FDA’s role to ensure that drugs are safe and 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.”

Back to Table of Contents

2. What the Proposal Would Change

According to the Federal Register notice, the proposed order, “if finalized, will amend Final Administrative Order OTC000026, to remove orally administered phenylephrine hydrochloride and phenylephrine bitartrate in an effervescent dosage as nasal decongestant active ingredients because they are not effective.” Phenylephrine hydrochloride is the form used in ordinary tablets and liquids; phenylephrine bitartrate is the form used in effervescent (fizzing, dissolved-in-water) products. The scientific review explains that the bitartrate form was added to the monograph only on the basis of data showing it behaves comparably to the hydrochloride, so the finding applies to both.

The scientific review lists the doses the monograph currently allows. For adults and children 12 years and over: 10 mg of phenylephrine hydrochloride every 4 hours, not more than 60 mg in 24 hours (or 15.6 mg of the bitartrate every 4 hours, not more than 62.4 mg in 24 hours). Lower doses are listed for children aged 6 to under 12 and 2 to under 6. The review notes that the FDA’s determination on doses for children under 12 “was based entirely on historical use and not clinical data in those age groups,” extrapolated from adult data.

The notice adds that the order also makes “minor stylistic and formatting changes” to the monograph, including removing references to historical Federal Register documents, “because OTC monographs are no longer modified through notice and comment rulemaking.”

If the order were finalized, the press release says, “drug products thereafter could no longer contain oral phenylephrine as a nasal decongestant,” and “the FDA would provide manufacturers with appropriate time to either reformulate drugs containing oral phenylephrine or remove such drugs from the market.” The scientific review adds that, once finalized, such products “will be deemed new drugs” — meaning they could be sold only under an approved new drug application.

Back to Table of Contents

3. Key Terms: OTC Monographs, GRASE and Administrative Orders

• OTC monograph. Most nonprescription medicines are not individually approved. Instead they follow a “monograph” — a rulebook for a category of products that lists the permitted active ingredients, doses and label wording. The Federal Register notice says Monograph M012 “describes the conditions under which OTC cold, cough, allergy, bronchodilator, and antiasthmatic drug products are generally recognized as safe and effective.”
• GRASE. “Generally recognized as safe and effective” — the legal standard an ingredient has to meet to be sold under a monograph. The scientific review quotes the regulation’s definition of effectiveness: “a reasonable expectation that, in a significant proportion of the target population, the pharmacological effect of the drug … will provide clinically significant relief of the type claimed.”
• Administrative order. According to the Federal Register notice, Monograph M012 is set out in Final Administrative Order OTC000026, which was deemed established by section 505G(b)(8) of the Act and took effect when the Coronavirus Aid, Relief, and Economic Security (CARES) Act was enacted on 27 March 2020. Monographs are now changed by administrative orders — first a proposed order open for comment, then a final order — rather than by the older notice-and-comment rulemaking.
• Federal Register and docket. The Federal Register is the U.S. government’s daily official journal of agency rules and notices. A docket is the public file for one action (here FDA-2024-N-4734) where comments and supporting documents are collected.
• Nasal decongestant. A medicine meant to relieve a stuffy nose. Oral phenylephrine is taken by mouth; the same chemical is also sold as a nasal spray, which this proposal does not cover.

Back to Table of Contents

4. The Background the Documents Give: 1976 to 2023

The scientific review traces the history. In the Federal Register of 9 September 1976 (41 FR 38312) the FDA issued an advance notice of proposed rulemaking based on the recommendations of an Advisory Review Panel on OTC cold, cough, allergy, bronchodilator and antiasthmatic products. That panel reviewed oral phenylephrine data that included 14 studies with clinical efficacy data and concluded that oral phenylephrine is effective as a nasal decongestant. The FDA’s formal determination followed in a final rule published 23 August 1994 (59 FR 43409). The press release refers to this as “the determination made 30 years ago that oral phenylephrine was effective as a nasal decongestant.”

The review records two citizen petitions on oral phenylephrine, one in 2007 and one in 2015 (docket FDA-2015-P-4131). On 14 December 2007 the FDA convened its Nonprescription Drugs Advisory Committee to discuss the safety and effectiveness of oral phenylephrine and to address the 2007 petition. The review says that committee “recommended that additional trials be conducted” and advised on how they should be run.

On 11–12 September 2023 the Nonprescription Drugs Advisory Committee met again. According to the press release, the committee “discussed new data on the effectiveness of orally administered phenylephrine and unanimously concluded that the current scientific data do not support” the effectiveness of the monograph’s recommended dosage of oral phenylephrine as a nasal decongestant.

Back to Table of Contents

5. Why the FDA Set Aside the Older Studies

The scientific review re-examined the studies the 1970s panel relied on. It found that only 12 of the 14 studies provided efficacy information that could be evaluated, and ten of them were submitted by the manufacturer of a brand-name oral phenylephrine product of that era. The review describes several problems:

• The measure used. The studies used nasal airway resistance — a machine measurement of airflow through the nose — rather than patients’ own ratings of congestion. The review states that this measure “has not been clinically validated as an endpoint” and has “inherent variability and methodological issues,” and that since the 1990s every topical nasal drug and second-generation antihistamine approved by the FDA has used patient-rated symptom scores instead.
• The illness studied. All but one study was done in people with the common cold, which the review calls “highly variable” as a setting for measuring congestion, compared with allergic rhinitis.
• Size and statistics. The studies were small (fewer than 50 participants each), mostly single-centre crossover studies with no sample-size calculation and no adjustment for testing many time points.
• Inconsistent results. A table in the review shows that, across the ten manufacturer studies, more participants at the 10 mg dose were in studies classed as negative (71) than positive (42).

The review concludes that, “due to significant issues with study design, methodology, disease context, conduct, and statistical analysis, the historical studies cannot be relied upon to provide evidence of efficacy of oral phenylephrine as a nasal decongestant.”

Back to Table of Contents

6. The Newer Clinical Trials the FDA Reviewed

The review describes five newer studies, all in adults, and reports that oral phenylephrine did not beat placebo in any of them:

• Allergen chamber study, Vienna, 2006 (39 adults with seasonal allergies). A single 12 mg dose of oral phenylephrine was compared with pseudoephedrine 60 mg and placebo in people exposed to grass pollen in a controlled chamber. There was no difference in nasal congestion scores between phenylephrine and placebo; pseudoephedrine produced an average 6-hour decrease of 21.7 percent in congestion score.
• Allergen chamber study, Ontario, 2007 (379 adults with ragweed allergy). A single 10 mg dose of phenylephrine served as a comparator for an allergy-drug combination. The review reports “no statistical difference between PE and placebo.”
• Dose-ranging trial, 2011 (539 adults with seasonal allergies). Doses of 10, 20, 30 and 40 mg every 4 hours for 7 days were compared with placebo. None of the four doses differed from placebo; the review calls the trial “substantive evidence that oral PE at dosages of 10 mg to 40 mg are not effective as a nasal decongestant.”
• Extended-release trial, 2011 (575 adults with fall allergies). A 30 mg modified-release tablet was compared with placebo across 29 sites. Mean improvement in congestion score was −0.394 with phenylephrine and −0.412 with placebo. The review calls this “high-quality evidence that PE is not an effective nasal decongestant when administered orally in a 30 mg MR formulation.”
• Common-cold trial, Canada, 2017–18 (193 adults analysed). A 30 mg extended-release tablet and a 12 mg immediate-release capsule were compared with placebo. Neither differed significantly from placebo (p = 0.569 and p = 0.300); the review notes that only partial results were publicly posted.

The review’s summary: “In three studies conducted after the 2007 meeting, oral PE failed to demonstrate any benefit over placebo,” and in the two allergen-chamber studies “oral PE failed to demonstrate benefit over placebo.” Its overall conclusion adds that “there are no clinical data demonstrating that oral PE is effective as a nasal decongestant at any dosage.”

Back to Table of Contents

7. The Pharmacology: How Little Active Drug Reaches the Blood

The scientific review offers an explanation for the trial results. Oral phenylephrine “is known to undergo extensive presystemic metabolism, with a majority of the metabolism taking place within the gut wall” — meaning most of the swallowed dose is changed into other compounds before it reaches the bloodstream. In a small single-dose study of 14 people presented to the 2007 advisory committee, the active parent drug made up less than 1 percent of the total phenylephrine-related material in the plasma after a 10 mg dose. Laboratory tests presented at the same meeting found no detectable activity at the relevant adrenergic receptors for the three main metabolites.

The review compares the numbers: the peak blood level of active phenylephrine after a 10 mg oral dose (about 0.65 ng/mL) was below the concentrations needed to activate the target receptors in the laboratory (2.3 and 16.9 ng/mL). It concludes that “oral phenylephrine has no meaningful systemic exposure within the dosage limits and in the dosage forms” set out in the monograph, and that this explains the lack of efficacy. By contrast, the review notes, phenylephrine given into a vein at less than 1 mg shows measurable effects, and the lowest nasal-spray strength the monograph allows is roughly a million times more concentrated than the peak blood level after a 10 mg oral dose.

Back to Table of Contents

8. What the FDA Found on Safety

The proposal is not based on a safety problem. The scientific review states that the FDA “proposes that no safety signal was identified for oral PE within the dosage limits and in the dosage forms allowed under OTC Monograph M012.” The FDA’s consumer page says that, “even though oral phenylephrine is widely used, FDA identified very few cases of serious side effects when oral phenylephrine is taken by consumers as directed in the label of the drug product.”

The review describes what the agency looked at: a 2009 blood-pressure safety study of a 30 mg extended-release tablet in 116 adults, which found no meaningful difference in mean systolic blood pressure from placebo (118.3 versus 118.6 mm Hg), and reports in the FDA Adverse Event Reporting System, the national poison-centre database and the medical literature. Those reports “suggest that PE is associated with CV [cardiovascular] and neurologic AEs [adverse events], which is expected and addressed by the current labeling.”

Two further findings in the review bear on safety. Analysis of the adverse-event reports “indicated that consumers used oral PE products at higher doses, or at more frequent dosing intervals, or for longer durations of therapy than specified on the label, which might reflect PE’s poor oral bioavailability and lack of effectiveness.” And the review states that “available data suggests that a much higher dose of phenylephrine would be needed to achieve a clinically meaningful outcome which would raise significant questions about safety.”

Back to Table of Contents

9. What the Proposal Does Not Do

• It does not remove any product from sale now. The press release: “For now, companies may continue to market OTC monograph drug products containing oral phenylephrine as a nasal decongestant. This is a proposed order. Only a final order will affect what products can be marketed.” The consumer page says people whose product contains oral phenylephrine “may continue to use it.”
• It does not cover phenylephrine nasal sprays or other non-oral forms. The press release says the action “is only related to orally administered phenylephrine and not the nasal spray form,” and the consumer page says it does not affect nasal sprays or topical products. The scientific review also lists phenylephrine given into a vein, in anorectal products and in eye products as outside its scope.
• It is not a safety finding. The release says the proposal “is based on effectiveness concerns, not on safety concerns.”
• It does not change how other ingredients in combination products work. Many products combine phenylephrine with, for example, acetaminophen or dextromethorphan; the release states that “the presence of oral phenylephrine in these medicines does not affect how other active ingredients work.”
• It does not ask pharmacies to pull products. The consumer page notes that pharmacies “may choose to remove some products … even though FDA is not requesting pharmacies do this.”

Back to Table of Contents

10. Other Options the FDA Lists for Nasal Congestion

The FDA’s consumer page lists, as the agency’s own information, other nonprescription products used for nasal congestion from colds or allergies: oral pseudoephedrine, and nasal sprays containing nasal decongestants, nasal corticosteroids or nasal antihistamines. It also lists non-drug options, “especially for children”: cool-mist humidifiers, saline nose drops or sprays, and nasal suctioning with a bulb syringe. The same page says it is “important to seek the help of a healthcare professional if symptoms of nasal congestion do not improve within 7 days or are accompanied by fever.”

The consumer page also points out that many cough and cold products contain more than one active ingredient, that acetaminophen appears in many of them, and that taking more than the maximum daily dose of acetaminophen “can lead to liver failure.” The release quotes the director of CDER’s Office of Nonprescription Drug Products: “Consumers should know that a range of safe and effective drugs and other treatments is available to temporarily relieve congestion symptoms due to allergies or a common cold. Consumers can also talk to their doctor or pharmacist about ways to treat these symptoms.” Decisions about any medicine belong with a clinician or pharmacist.

Back to Table of Contents

11. Dates and Legal Status as of 11 October 2026

• 31 October 2024 — date of the Federal Register notice.
• 4 November 2024 — date of the scientific review supporting the proposed order.
• 7 November 2024 — FDA announces the proposal.
• 8 November 2024 — notice of availability published (89 FR 88787); proposed order OTC000036 posted in OTC Monographs@FDA; comment period opens.
• 7 May 2025 — comment period closed at 11:59 p.m. Eastern Time. The notice states that late comments “will not be considered.”

Status: proposed, not final. As of 11 October 2026 the OTC Monographs@FDA order page still lists OTC000036 as a “Proposed Order,” and a query of the Federal Register for FDA documents mentioning phenylephrine, the docket number or the order number, published from 9 November 2024 through 11 October 2026, returned no final order, withdrawal or other document changing the proposal’s status. Oral phenylephrine therefore remains a permitted nasal decongestant ingredient under Monograph M012 for now. The press release says that if, after considering comments, the FDA concludes oral phenylephrine is not effective, it “will issue a final order”; the consumer page says “FDA will let the public know when it takes any future actions.”

Back to Table of Contents

12. How It Fits the FDA’s Earlier Handling of Oral Phenylephrine

The proposal is the latest step in a review the documents trace back almost five decades: the 1976 advisory panel that found oral phenylephrine effective, the 1994 final rule that adopted that finding, the 2007 citizen petition and advisory committee meeting that called for new trials, the trials run between 2006 and 2018 that found no benefit over placebo, the 2015 citizen petition, and the September 2023 advisory committee meeting that unanimously found the current data do not support effectiveness at the monograph dose. The press release says the agency’s review covered “the historical data that were used to support the determination made 30 years ago” and “newer clinical data on oral phenylephrine that have since become available.”

The proposal also follows the newer process for changing an OTC monograph: the Federal Register notice explains that, since the CARES Act of 2020, monographs are amended by administrative order under section 505G rather than by notice-and-comment rulemaking, and that the proposed order is viewed and commented on through the OTC Monographs@FDA portal. Other FDA actions of 2024 are listed on the 2024 FDA actions page.

Back to Table of Contents

13. Primary Documents

1. U.S. Food and Drug Administration (2024). FDA Proposes Ending Use of Oral Phenylephrine as OTC Monograph Nasal Decongestant Active Ingredient After Extensive Review. News release, 7 November 2024 — FDA news release
2. Food and Drug Administration, HHS (2024). Amending Over-the-Counter Monograph M012: Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products for Over-the-Counter Human Use; Notice of availability. Federal Register 89:88787, 8 November 2024, Docket No. FDA-2024-N-4734 — FR Doc. 2024-25910
3. U.S. Food and Drug Administration. Proposed Administrative Order OTC000036, order page in OTC Monographs@FDA (status shown: “Proposed Order”; viewed 11 October 2026), Docket No. FDA-2024-N-4734 — OTC000036 order page
4. U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Office of Nonprescription Drugs (2024). Scientific Review Supporting Proposed Administrative Order OTC000036, 4 November 2024 (PDF) — Scientific review (PDF)
5. U.S. Food and Drug Administration. Key Information about Nonprescription, Over-the-Counter (OTC), Oral Phenylephrine. Consumer page, content current as of 7 November 2024 — FDA consumer page

Back to Table of Contents

Key Research Papers

1. Hatton RC, Winterstein AG, McKelvey RP, Shuster J, Hendeles L (2007). Efficacy and safety of oral phenylephrine: systematic review and meta-analysis. Annals of Pharmacotherapy 41(3):381-390 — PubMed PMID: 17264159
2. Kollar C, Schneider H, Waksman J, Krusinska E (2007). Meta-analysis of the efficacy of a single dose of phenylephrine 10 mg compared with placebo in adults with acute nasal congestion due to the common cold. Clinical Therapeutics 29(6):1057-1070 — PubMed PMID: 17692721
3. Horak F, Zieglmayer P, Zieglmayer R, Lemell P, Yao R, Staudinger H, Danzig M (2009). A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna Challenge Chamber. Annals of Allergy, Asthma & Immunology 102(2):116-120 — PubMed PMID: 19230461
4. Day JH, Briscoe MP, Ratz JD, Danzig M, Yao R (2009). Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit. Annals of Allergy, Asthma & Immunology 102(4):328-338 — PubMed PMID: 19441605
5. Meltzer EO, Ratner PH, McGraw T (2015). Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo-controlled study. Journal of Allergy and Clinical Immunology: In Practice 3(5):702-708 — PubMed PMID: 26143019
6. Hatton RC, Hendeles L (2015). Over-the-counter oral phenylephrine: a placebo for nasal congestion. Journal of Allergy and Clinical Immunology: In Practice 3(5):709-710 — PubMed PMID: 26362551
7. Meltzer EO, Ratner PH, McGraw T (2016). Phenylephrine hydrochloride modified-release tablets for nasal congestion: a randomized, placebo-controlled trial in allergic rhinitis patients. Annals of Allergy, Asthma & Immunology 116(1):66-71 — PubMed PMID: 26560899

Papers 3, 4, 5 and 7 report trials described in the FDA’s 2024 scientific review (section 6 above). Papers 1 and 2 are meta-analyses of the older single-dose studies that reached different conclusions; they are listed for context, and the FDA’s own assessment of those older studies is in section 5.

PubMed Topic Searches

1. PubMed: oral phenylephrine and nasal congestion
2. PubMed: oral phenylephrine bioavailability
3. PubMed: nasal decongestants in allergic rhinitis, placebo-controlled

Back to Table of Contents

Connections

• FDA Actions of 2024
• FDA and Regulation
• Common Cold
• Allergic Rhinitis (Hay Fever)
• Sinusitis
• Cold and Flu Natural Treatments
• Honey as a Cough Suppressant
• FDA Approves the First Needle-Free Epinephrine for Anaphylaxis (2024)
• FDA Clears the First Over-the-Counter Continuous Glucose Monitor (2024)
• FDA Starts an Acetaminophen-in-Pregnancy Label Change (2025)

Back to Table of Contents