Manufacturers Consider Design Changes For OTC Propylhexedrine Nasal Decongestant Inhalers

"Manufacturers are already working on possible solutions to address the concerns and will work with the Agency to implement any appropriate measures,” says CHPA senior VP  Barbara Kochanowski.

Drug manufacturers are aware of the US Food and Drug Administration’s concerns about abuse of propylhexedrine and are considering changes to OTC nasal decongestant inhalers to prevent removal of the ingredient from the products.

The Consumer Healthcare Products Association says manufacturers will work with the agency to ensure propylhexedrine, currently marketed OTC in the US only under the brand Benzedrex, remains available as an ingredient safe for use under its labeled indication, directions and dosage.

“Manufacturers take very seriously the FDA’s concerns about possible misuse and abuse of OTC products. Manufacturers are already working on possible solutions to address the concerns and will work with the Agency to implement any appropriate measures as quickly as possible,” said Barbara Kochanowski, CHPA’s senior vice president, regulatory and scientific affairs.

In a 26 March statement to HBW Insight, Kochanowski noted that the FDA’s announcement the previous day stated “propylhexedrine is a safe and effective ingredient when used as directed on the Drug Facts label.”

“As with any medicine, misuse and abuse can lead to negative health consequences. While serious adverse events appear to be relatively rare, the increases in poison center calls over the last couple of years is concerning and we applaud FDA for their ongoing vigilance,” she said.

The FDA also advised in its announcement that “reports of individuals abusing and misusing propylhexedrine have increased in recent years” and that abuse of the ingredient available under an OTC monograph a can lead to serious harm such as heart and mental health problems. (Also see "Propylhexedrine Abuse Prompts US FDA To Suggest OTC Nasal Inhaler Modifications, Smaller Size" - HBW Insight, 25 Mar, 2021.)

Propylhexedrine can be abused when removed from inhalers. The agency said it’s asking all manufacturers of OTC nasal decongestant inhalers containing the ingredient to consider product design changes that support its safe use.

It suggests making changes that create a physical barrier in the product to prevent tampering and cutting the amount of medicine the device contains to reduce the risk of serious side effects if abused or misused.

According to the product label, a dose of Benzedrex contains 250 mg propylhexedrine.

Regulatory Options Limited

Public health researchers also have concerns about propylhexedrine’s potential for abuse. The ingredient was developed in the mid-1900s as a substitute for amphetamine, once the active ingredient in Benzedrex inhalers, in response to abuse and deaths from amphetamine extracted from the inhalers. Propylhexedrine is related to amphetamine but has been structurally modified to be less dangerous.

Moving propylhexedrine, or any ingredient currently available nonprescription in the US, to Rx-only is a regulatory path the FDA almost certainly won’t take. Limiting sales of pseudoephedrine and other amphetamines available in OTC antihistamines was done through legislation, the Combat Methamphetamine Epidemic Act, not through rulemaking by the FDA.

The Combat Meth Act, enacted to prevent the diversion of PSE for illicit production of methamphetamine, limits amounts of pseudoephedrine, ephedrine and norpseudoephedrine OTC drugs that consumers can purchase daily and monthly.

Two states imposed more stringent restrictions by requiring prescriptions for all drugs containing the ingredients, but one, Mississippi, recently rescinded its law effective in January 2022, and the other, Oregon, is considering dropping its Rx requirement. (Also see "Pseudoephedrine Tide Turns: Nonprescription Sales Return In Mississippi, Oregon Mulls Change" - HBW Insight, 22 Mar, 2021.)

Several members of Congress also have pushed for a law banning sales to minors of dextromethorphan-containing OTC decongestants. The proposal hasn’t moved in Congress, but 20 states have imposed the age requirement, as have numerous local governments. State or local age restrictions on dextromethorphan sales, which have the drug industry’s support, have slowed the rate of abuse of the ingredient. (Also see "HBW Legislative News: Another Federal CR, Michigan On DXM List, Senators Say Supplements Are 'Medical Expenses'" - HBW Insight, 21 Nov, 2019.)

Environmental concerns drove the FDA’s requirement for reformulating OTC emergency asthma inhalers with epinephrine with hydrofluoroalkane as a propellant, replacing ozone-depleting chlorofluorocarbon. (Also see "OTC Primatene Mist Returns: Market Future Bright After Cloudy NDA History" - HBW Insight, 9 Nov, 2018.)