U.S. Food and Drug Administration (FDA) Warns That Abuse of the Nasal Decongestant Propylhexedrine Causes Serious Harm (2021)

Table of Contents

1. What the U.S. Food and Drug Administration Announced on March 25, 2021
2. What the U.S. Food and Drug Administration Asked Manufacturers to Do
3. What Propylhexedrine Is and How It Is Labeled
4. What the U.S. Food and Drug Administration Found in Poison Control Center Data
5. What the U.S. Food and Drug Administration Found in Its Own Reports and Emergency Department Data
6. What the Published Medical Literature Showed
7. The Harms the U.S. Food and Drug Administration Describes
8. What the U.S. Food and Drug Administration Tells Consumers and Health Care Professionals
9. What the Warning Does Not Do
10. Dates and Legal Status as of October 18, 2026
11. How It Fits Other U.S. Food and Drug Administration Actions on Misused Medicines
12. Primary Documents
13. Key Research Papers
14. Connections
15. Featured Videos

1. What the U.S. Food and Drug Administration Announced on March 25, 2021

The action took the form of a U.S. Food and Drug Administration Drug Safety Communication, dated March 25, 2021 — a public notice, written in question-and-answer form, in which the agency sets out a safety concern about a medicine, what it is doing about it and what it found. It was published on the U.S. Food and Drug Administration’s website, with a PDF copy, a Spanish version and a recorded Drug Safety Podcast. It was not a Federal Register document, so it carries no Federal Register citation and no public docket (the numbered public file where an agency collects comments on a proposal).

The communication’s headline reads: “U.S. Food and Drug Administration warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm,” with the subtitle “This includes heart and mental health problems or death.” Its opening answer states that the complications “include fast or abnormal heart rhythm, high blood pressure, and paranoia,” and that “Reports of individuals abusing and misusing propylhexedrine have increased in recent years.”

In the same paragraph the U.S. Food and Drug Administration adds a sentence that frames the whole warning: “Propylhexedrine is safe and effective when used as directed.” The concern the agency describes is with use outside the directions on the label, not with the medicine used as labeled.

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2. What the U.S. Food and Drug Administration Asked Manufacturers to Do

Under the heading “What is U.S. Food and Drug Administration doing?” the agency wrote: “We are requesting that all manufacturers of over-the-counter (OTC) propylhexedrine nasal decongestant inhalers consider product design changes that support its safe use.”

The U.S. Food and Drug Administration gave two examples of the kind of change it had in mind:

• A physical barrier. “modifying the product to create a physical barrier that would make tampering with the device and abusing the propylhexedrine inside more difficult.”
• Less medicine per device. “decreasing the amount of medicine the device contains could also reduce the risk of serious side effects if abused or misused.”

The request asks manufacturers to consider these changes; the communication does not state a deadline or require a particular design. The U.S. Food and Drug Administration closed the section with: “We continue to evaluate this safety issue and will determine if additional U.S. Food and Drug Administration actions are needed.”

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3. What Propylhexedrine Is and How It Is Labeled

The U.S. Food and Drug Administration describes propylhexedrine as “a nasal decongestant that is available over-the-counter in an inhaler.” “over-the-counter” means over the counter: it can be bought without a prescription. According to the communication, it “is used short term to temporarily relieve nasal congestion due to colds, hay fever, or other upper respiratory allergies,” and it “works by reducing swelling and inflammation of the mucous membrane lining of the nose.”

The communication restates the labeled directions:

• For adults and children older than 6 years, the labeled dose is two inhalations in each nostril, not more often than every 2 hours.
• For children younger than 6, the label directs families to a health care professional before use.
• The label limits use to no more than 3 days at a time; the U.S. Food and Drug Administration notes that “Prolonged use may cause nasal congestion to recur or worsen.”

The U.S. Food and Drug Administration lists the common side effects of the medicine when used as labeled as “temporary discomfort such as burning, stinging, sneezing, or increasing nasal discharge.” The communication also states that the medicine was, at the time, marketed under only one brand name (not named here).

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4. What the U.S. Food and Drug Administration Found in Poison Control Center Data

The U.S. Food and Drug Administration’s Data Summary explains that, “In response to increasing reports of abuse and misuse of propylhexedrine,” the agency reviewed calls to U.S. poison control centers, case reports submitted to the U.S. Food and Drug Administration and published in the medical literature, cases seen in U.S. emergency departments, and an observational study.

From the national poison-center database (the American Association of Poison Control Centers’ National Poison Data System), the U.S. Food and Drug Administration reported:

• 460 cases between January 1, 2000, and December 31, 2019: 415 of abuse and 45 of misuse. The Data Summary notes that poison control centers define misuse as “the intentional, improper use for a reason other than self-harm or for achieving a psychotropic effect.”
• A rising trend. Annual cases went from 11 in 2011 to 74 in 2019, “with abuse cases making up the majority of this increase”; the Data Summary describes “a sharp rise starting in 2015.”
• Who was involved. The cases involved people aged 12 to 68, and most were male.
• Alone or with other substances. Most cases (345, or 75 percent) involved propylhexedrine alone. When other substances were involved (115 cases, 25 percent), frequent co-exposures included cold and cough medicines, alcohol, antidepressants, opioids, sedatives, hypnotics and antipsychotics, and a variety of stimulants and street drugs.
• Severity. Of the 460 cases, 21 had adverse effects that were life-threatening, and 13 of those resulted in intensive care unit admissions.

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5. What the U.S. Food and Drug Administration Found in Its Own Reports and Emergency Department Data

The U.S. Food and Drug Administration also reviewed two further sources: the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), the database that holds side-effect reports sent voluntarily to the agency, from January 1969 through January 31, 2020; and the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project (NEISS-CADES), which tracks emergency department visits, from January 1, 2016, through December 31, 2018.

• 60 U.S. cases of serious adverse events related to propylhexedrine abuse, misuse, dependence or withdrawal: 53 from FAERS and 7 from emergency department visits. Among them were 57 cases of abuse, 18 of dependence, three of withdrawal and one of misuse.
• Who was involved. Most were male (55, or 92 percent) and adults aged 18 to 65 (40, or 66 percent).
• Severity. Twenty-three of the 60 experienced life-threatening adverse events or hospitalization, and nine died.
• The nine deaths. In six, propylhexedrine abuse combined with other substances contributed to the cause of death; in one, propylhexedrine abuse alone was the cause. For one, the cause of death was not reported. The last was a death from injuries in a motor vehicle accident in a person whose post-mortem blood level of propylhexedrine was in the toxic range.
• Timing. The communication notes that “Some harms occurred several hours after abuse.”

The U.S. Food and Drug Administration adds: “There are likely additional cases that we have not identified.”

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6. What the Published Medical Literature Showed

The U.S. Food and Drug Administration reviewed “49 case reports and an observational study published in the medical literature,” and states that “These publications showed similar findings compared to the cases identified from poison control calls and emergency department visits and the cases reported to U.S. Food and Drug Administration.”

• Most of the published reports described young men, and there were 18 deaths among them.
• In older reports, the most common adverse events were ischemic limb injury (loss of blood supply to an arm or leg), cranial nerve dysfunction, psychosis, cardiomyopathy (heart-muscle damage), adrenergic overstimulation (an overactive “fight or flight” response) and anxiety or agitation.
• More recent reports were mainly about psychosis, adrenergic stimulation and agitation.
• A retrospective study of single-substance propylhexedrine abuse cases documented by U.S. poison control centers from 2007 to 2016 identified 283 calls, rising each year from 16 in 2007 to 58 in 2016; 66 percent involved males. Most adverse effects were sympathomimetic (stimulant-like), and no deaths were noted, “although deaths are expected to be under-ascertained in poison control center data.”

The communication lists its 25 references, several of which appear in the Key Research Papers section below.

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7. The Harms the U.S. Food and Drug Administration Describes

Across the data sources, the U.S. Food and Drug Administration lists the most commonly reported side effects of abuse and misuse as rapid heart rate, agitation, high blood pressure, chest pain, tremor, hallucinations, delusions, confusion, nausea and vomiting.

In its information for consumers, the U.S. Food and Drug Administration describes the serious heart and mental health problems as including “fast or abnormal heart rhythms, high blood pressure, heart attack, heart failure, agitation, delusions, paranoia, hallucinations, and death even after a few hours of abuse or misuse.” Related conditions are described on the site’s Arrhythmia, Hypertension, Heart Attack and Heart Failure pages.

In its information for health care professionals, the U.S. Food and Drug Administration lists the major problems that may have to be managed during intoxication: “severe agitation, tachycardia, hypertension, myocardial infarction, hyperthermia, stroke, bowel obstruction, pulmonary hypertension, and seizures.” It adds: “Long-term use can also lead to lung damage, arrhythmias, and cardiac damage.” The communication states that there is no specific reversal agent (no antidote) for acute propylhexedrine intoxication, so care is symptomatic and supportive.

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8. What the U.S. Food and Drug Administration Tells Consumers and Health Care Professionals

The communication contains the U.S. Food and Drug Administration’s own guidance to two audiences. It is reported here as the agency’s statement.

To consumers, the U.S. Food and Drug Administration states that propylhexedrine is to be used only according to the directions on its Drug Facts label (the standard information panel on an over-the-counter medicine), and warns that using it “in ways other than by inhalation” can cause serious harm, including heart and mental health problems, some of which can lead to death. The U.S. Food and Drug Administration directs people to call 911 or poison control (1-800-222-1222) for anyone using propylhexedrine who has severe anxiety or agitation, confusion, hallucinations or paranoia; a rapid heartbeat or abnormal heart rhythm; or chest pain or tightness. Its consumer section also notes that inhalers are not to be shared, because use by more than one person “may spread infection,” and points people with questions to a pharmacist or health care professional.

To health care professionals, the U.S. Food and Drug Administration writes that “some individuals are abusing or misusing propylhexedrine, particularly using it by routes other than nasal inhalation,” which “can result in serious cardiac and psychiatric adverse events or death.” In a suspected overdose, the agency describes trying to determine whether a patient used propylhexedrine alone or with other substances, and it asks clinicians to counsel consumers not to exceed the labeled dose.

Both audiences are asked to report side effects to the U.S. Food and Drug Administration’s MedWatch program.

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9. What the Warning Does Not Do

• It does not remove propylhexedrine from sale. The medicine stays available over the counter; the communication restates its labeled use and says it “is safe and effective when used as directed.”
• It does not make it prescription-only. Nothing in the communication changes how it is sold.
• It does not change the Drug Facts label. The communication’s request to manufacturers concerns the design of the inhaler, not new label wording.
• It does not order a redesign. Manufacturers are asked to consider design changes; no specific design or deadline is set.
• It is not a rule. A Drug Safety Communication is a public notice, not a regulation published in the Federal Register, and it opened no comment period.

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10. Dates and Legal Status as of October 18, 2026

• March 25, 2021 — Drug Safety Communication issued, with the request to manufacturers.
• April 13, 2021 — the date the U.S. Food and Drug Administration web page gives as “Content current as of.”
• January 20, 2022 — the “Content current as of” date on the accompanying Drug Safety Podcast page.

Status as of October 18, 2026: the warning stands as issued, and no later U.S. Food and Drug Administration action on propylhexedrine was found. A Federal Register check for documents mentioning propylhexedrine from January 1, 2021, through October 18, 2026, returned none, and the communication itself had not been updated with any follow-up action. Propylhexedrine remains an over-the-counter nasal decongestant. The communication does not report whether any manufacturer changed its inhaler design in response to the request.

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11. How It Fits Other U.S. Food and Drug Administration Actions on Misused Medicines

The propylhexedrine warning was one of several Drug Safety Communications the U.S. Food and Drug Administration issued in 2021. Others covered here include the boxed warnings on JAK inhibitors and the removal of the strongest statin warning against use in pregnancy; the same year the agency also acted on hand-sanitizer safety and on a nitrosamine impurity in varenicline.

Later U.S. Food and Drug Administration actions covered here deal with the misuse of other medicines and substances, by different tools:

• In 2023 the U.S. Food and Drug Administration required updated boxed warnings on prescription stimulants describing the risks of misuse, abuse, addiction, overdose and death — a labeling requirement, where the 2021 propylhexedrine action was a design request.
• In 2024 the U.S. Food and Drug Administration warned retailers about tianeptine, a substance sold outside the approved-drug system.
• Also in 2024, a different over-the-counter decongestant was the subject of a U.S. Food and Drug Administration proposal to remove oral phenylephrine — on the separate question of whether it works, not on misuse.

Background on substance use, from a medical rather than regulatory angle, is on the site’s Addiction and Substance Use Disorders page, and stimulant harms from other products are covered under Stimulants in Weight-Loss and Energy Products.

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12. Primary Documents

1. U.S. Food and Drug Administration. U.S. Food and Drug Administration warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm: This includes heart and mental health problems or death. U.S. Food and Drug Administration Drug Safety Communication, March 25, 2021 (content current as of April 13, 2021). Not a Federal Register document; no docket — fda.gov Drug Safety Communication
2. U.S. Food and Drug Administration. Drug Safety Communication, March 25, 2021 (PDF version, 93 KB) — fda.gov Drug Safety Communication PDF
3. U.S. Food and Drug Administration. U.S. Food and Drug Administration Drug Safety Podcast: U.S. Food and Drug Administration warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm (content current as of January 20, 2022) — fda.gov Drug Safety Podcast
4. U.S. Food and Drug Administration. Spanish-language version of the Drug Safety Communication (La U.S. Food and Drug Administration advierte que el abuso y el uso indebido del descongestionante nasal propilhexedrina causan daños graves) — fda.gov Comunicado de seguridad
5. U.S. Food and Drug Administration. Drug Safety Communications (index of all communications) — fda.gov Drug Safety Communications

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Key Research Papers

1. Pakkir Maideen NM, Rashid SA (2026). Cardiovascular and Cerebrovascular Events Linked to Abuse and Misuse of Sympathomimetic Nasal Decongestants: A Narrative Review of Clinical Evidence. Cardiovascular & Hematological Agents in Medicinal Chemistry 24(1):33-44 — PubMed PMID: 41603177
2. Horowitz KM, Cassidy E, Temple C (2024). Neurologic Deficits Following Oral Misuse of the Nasal Decongestant Propylhexedrine. Journal of Medical Toxicology 20(4):427-429 — PubMed PMID: 39103667
3. Teja N, Dodge CP, Stanciu CN (2020). Abuse, Toxicology and the Resurgence of Propylhexedrine: A Case Report and Review of Literature. Cureus 12(10):e10868 — PubMed PMID: 33178521
4. Fernandez Julia P, Francis EM (2012). Propylhexedrine: a vintage drug of abuse, rediscovered. Journal of Psychoactive Drugs 44(3):277-279 — PubMed PMID: 23061329
5. Holler JM, Vorce SP, McDonough-Bender PC, Magluilo J Jr, Solomon CJ, Levine B (2011). A drug toxicity death involving propylhexedrine and mitragynine. Journal of Analytical Toxicology 35(1):54-59 — PubMed PMID: 21219704
6. Smith DE, Wesson DR, Sees KL, Morgan JP (1988). An epidemiological and clinical analysis of propylhexedrine abuse in the United States. Journal of Psychoactive Drugs 20(4):441-442 — PubMed PMID: 2907528
7. Croft CH, Firth BG, Hillis LD (1982). Propylhexedrine-induced left ventricular dysfunction. Annals of Internal Medicine 97(4):560-561 — PubMed PMID: 6127046

The first paper is a 2026 narrative review of heart and brain-circulation events reported with the abuse and misuse of stimulant-type nasal decongestants. The second and third are case reports published around and after the U.S. Food and Drug Administration warning; a 2019 conference poster with the same title as the third, by two of its authors, is in the U.S. Food and Drug Administration’s reference list. The last four — a review of the drug’s re-emergence, a toxicology death report, a 1980s U.S. analysis and an early report of heart-muscle dysfunction — are among the literature the U.S. Food and Drug Administration cites in its Data Summary.

PubMed Topic Searches

1. PubMed: propylhexedrine
2. PubMed: propylhexedrine toxicity
3. PubMed: nasal decongestant misuse

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Connections

• U.S. Food and Drug Administration Actions of 2021
• U.S. Food and Drug Administration and Regulation
• Allergic Rhinitis (Hay Fever)
• Sinusitis
• Addiction and Substance Use Disorders
• Arrhythmia
• Hypertension
• Heart Attack
• Heart Failure
• Pulmonary Hypertension
• Stimulants in Weight-Loss and Energy Products
• Oral Phenylephrine Removal Proposal (2024)
• Prescription Stimulant Boxed Warnings (2023)
• Tianeptine Retailer Warning (2024)
• JAK Inhibitor Boxed Warnings (2021)
• Statin Pregnancy Warning Removed (2021)
• Hand Sanitizer Safety Actions (2021)
• Varenicline Nitrosamine Recall and Limit (2021)

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