FDA Warns Abuse and Misuse of Over-the-Counter Nasal Decongestant Propylhexedrine (BENZEDREX) Causes Serious Harm

On March 25, 2021, the Food and Drug Administration (FDA) issued a Drug Safety Communication warning that abuse and misuse of the over-the-counter nasal decongestant drug propylhexedrine, a stimulant, can cause serious harm, including heart and mental health problems.[1]

Among the complications of abusing or misusing the drug highlighted by the agency were rapid or abnormal heart rhythms, high blood pressure and paranoia, which in some cases have led to hospitalization, disability or death. The FDA noted that reports of individuals abusing or misusing propylhexedrine have increased in recent years.

About propylhexedrine

Propylhexedrine, marketed only in a nasal-inhaler form under the brand name BENZEDREX, is used for short-term relief of nasal congestion due to colds, hay fever or other upper respiratory allergies.[2] The drug reduces swelling and inflammation of the mucous membranes inside the nose.

Each inhaler contains 250 milligrams (mg) of propylhexedrine, and each inhalation contains 0.4-0.5 mg.

The product labeling for Benzedrex recommends two inhalations in each nostril not more frequently than every two hours for adults and children 6 years of age or older (with adult supervision) and advises that the product should not be used for more than three consecutive days.[3]

The product labeling also includes the following warnings:

• Do not exceed the recommended dosage.
• This product may cause temporary discomfort such as burning, stinging, sneezing or an increase in nasal discharge.
• The use of this container by more than one person may spread infection.
• Frequent or prolonged use may cause nasal congestion to recur or worsen.
• Ill effects may result if taken internally.

The basis for the FDA’s warning

The FDA alert followed the agency’s review of several data sources, including calls to U.S. poison control centers, case reports submitted to the agency or published in the medical literature, and cases presenting to U.S. emergency departments.

Poison control center data

The FDA’s review of U.S. poison control center data identified 460 cases of propylhexedrine abuse (415 cases) or misuse (45 cases) for the 20-year period from January 2000 to December 2019. Misuse was defined by poison control centers as improper use of the drug for a reason other than self-harm or for achieving a psychological effect.

Annual cases of propylhexedrine abuse or misuse rose from 11 cases in 2011 to 74 cases in 2019. The individuals involved in these 460 cases were aged 12 to 68 years, and most were male. Three-quarters of the cases involved abuse or misuse of propylhexedrine alone. For the other cases, the additional substances that were most frequently abused or misused in combination with propylhexedrine included cold and cough medicines, alcohol, antidepressants, opioids, sedatives, antipsychotics, and a variety of other stimulants and street drugs.

The most common route of exposure was ingestion, followed by inhalation and injection. The most frequently reported signs and symptoms among these 460 cases were rapid heart rate, agitation, high blood pressure, nausea, chest pain, tremor, hallucinations or delusions, increased sweating, confusion and vomiting. In 21 cases, the adverse effects were considered life-threatening, and 13 required admission to an intensive care unit.

FDA adverse-event reports

The FDA’s search of its adverse-event reporting system for the period from January 1969 to January 2020 and of a national database tracking injuries and adverse events in emergency department patients for the period from January 2016 to December 2018 identified a total of 60 cases of serious adverse events linked to propylhexedrine abuse (57 cases), dependence (18 cases), withdrawal (three cases) or misuse (one case) (some cases involved more than one type of event).

Ninety-two percent of cases involved males, and two-thirds were adults aged 18 to 65. Oral ingestion (19 cases) and intravenous injection (13 cases) were the most common routes of exposure. The amount of propylhexedrine abused ranged from part of a single inhaler to the contents of 10 inhalers per day. The duration of abuse ranged from three days to 18 years.

Among the 60 patients, 23 experienced life-threatening adverse events or were hospitalized, and nine died. In six of the nine fatalities, propylhexedrine abuse in combination with other substances contributed to the death.

FDA actions

To address propylhexedrine abuse and misuse, the FDA initially has asked all manufacturers of the product to consider design changes to the inhalers to increase safety, such as modifying the design of the inhalers to make tampering with the device for the purpose of abusing the drug more difficult.

Decreasing the amount of the drug in each inhaler also is being considered as a way to reduce the risk of serious adverse events if the drug is misused or abused.

What You Can Do

You should only use propylhexedrine according to the directions on the product’s Drug Facts label. Do not exceed the recommended dose or use the drug for more than three days. Prolonged use may cause nasal congestion to recur or worsen.

Do not use propylhexedrine in ways other than by inhalation because doing so can cause serious harm, such as heart and mental health problems. Some of these problems can lead to death.

Seek medical attention immediately by calling 911 or poison control at 1-800-222-1222 for anyone using propylhexedrine who experiences the following:

• Severe anxiety or agitation, confusion, hallucinations or paranoia
• Rapid heartbeat or abnormal heart rhythm
• Chest pain or tightness

Talk to your pharmacist or health care professional if you have any questions about propylhexedrine, how to use it, or whether another medicine you are taking may interact with it.

If you or a family member experience adverse effects involving propylhexedrine, report the event to the FDA MedWatch program online at https://www.accessdata.fda.gov/scripts/medwatch/index.cfm.
 

References

[1] Food and Drug Administration. Drug safety communication: FDA warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm. March 25, 2021. https://www.fda.gov/media/146936/download. Accessed September 20, 2021.

[2] Food and Drug Administration. Drug safety communication: FDA warns that abuse and misuse of the nasal decongestant propylhexedrine causes serious harm. March 25, 2021. https://www.fda.gov/media/146936/download. Accessed April 6, 2021.

[3] B.F. Ascher & Co., Inc. Label: propylhexedrine inhalant (BENZEDREX). September 19, 2014. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=03a8ef3c-a808-6208-e054-00144ff8d46c&type=display. Accessed April 6, 2021.