Why Many Cold Medicines Don’t Work to Relieve Congestion

Citing the findings, doctors, pharmacists and groups including the American Academy of Allergy, Asthma and Immunology and the American College of Clinical Pharmacy have said the pills shouldn’t be sold.

“Why give something if it has no benefit?” said

Eli Meltzer,

an allergist in San Diego who performed some testing. “It’s a waste of money.” 

University of Florida pharmacy researchers who reviewed testing of the pills asked the Food and Drug Administration, in a citizen’s petition filed in 2015, to remove phenylephrine from the list of approved over-the-counter medicines.

The Food and Drug Administration told the researchers in 2016 that it was reviewing the request but was unable to reach a decision because the petition “raises complex issues requiring extensive review and analysis.”

The agency will respond to the researchers, an FDA spokeswoman said, but under federal law, can’t publicly discuss such filings.

Stefanie Ferreri, a professor at the University of North Carolina’s Eshelman School of Pharmacy, who isn’t involved in the petition but has followed the issue, said the FDA is probably not taking action because people face low risk of harm. 

“It’s not a safety concern so it’s not a priority of the FDA,” said Dr. Ferreri, who supports ending phenylephrine’s use in decongestants. 

The Consumer Healthcare Products Association, an industry trade group, said the medicines should remain on the market. The FDA recognized that phenylephrine works safely as an oral decongestant, and its member companies comply with federal regulations, a group spokesman said 

Johnson & Johnson,

which sells Tylenol and Benadryl, said phenylephrine is recognized by the FDA to work safely, and it evaluates the latest science, safety information and regulatory information on all its products. 

Reckitt Benckiser Group

PLC, which makes Mucinex, said it complies with federal regulations in all markets in which it operates.

Haleon

PLC, which makes versions of Theraflu that also contain phenylephrine, declined to comment. 

Phenylephrine is also the main ingredient in injections that increase blood pressure and in topical treatments to relieve hemorrhoids. As a decongestant, studies have found phenylephrine works when given via nasal spray. 

People take decongestant pills to relieve nasal congestion from a cold, flu or allergies. Over-the-counter products that treat cough, sinus and flu symptoms, including phenylephrine pills, generated about $5 billion in sales in 2021, according to the research firm IRI.  

The FDA first permitted use of phenylephrine in 1938. The drug was used in over-the-counter products starting at least in the 1950s. In 1976, the FDA included phenylephrine, along with two other main decongestant ingredients called phenylpropanolamine and pseudoephedrine, as over-the-counter products when it overhauled its regulations.

In 2000, the FDA asked manufacturers to remove phenylpropanolamine over concerns about an association with hemorrhagic stroke. Six years later, Congress restricted sales of products containing pseudoephedrine to behind the pharmacy counter because the ingredient can be used to make methamphetamine. 

Phenylephrine’s use in over-the-counter decongestants increased after use of the other two ingredients was restricted.  

Phenylephrine is now in more than 260 oral nose and sinus medicines, according to a 2020 paper published in JAMA Otolaryngology–Head & Neck Surgery. 

Like many older drugs, phenylephrine didn’t go through the rigorous clinical trials regulators require today for medications.

At least one company tested phenylephrine as a substitute for pseudoephedrine.

Schering-Plough,

which was later acquired by Merck & Co. and at the time made allergy medicine Claritin-D, tested whether swapping in phenylephrine would work. The company found phenylephrine was ineffective, according to published studies, and kept using pseudoephedrine in Claritin-D sold behind a pharmacy counter. 

Bayer AG

now makes Claritin-D, after acquiring it from Merck.

Other companies introduced products with phenylephrine instead of pseudoephedrine, however.

Leslie Hendeles and Randy Hatton, professors at the University of Florida pharmacy school who reviewed research on phenylephrine drugs in the 2000s, said they found insufficient evidence supporting phenylephrine effectiveness. 

In 2007, they first petitioned the FDA to review whether a 10 milligram phenylephrine pill was effective. Experts advising the agency voted, later that year, that the dosage may be effective, but more study was needed.

Since then, researchers have published at least four randomly-controlled studies. All found that phenylephrine wasn’t more effective at relieving congestion than placebo. Schering and then Merck funded the studies. 

In one company-sponsored study, researchers found the 10 milligram doses as well as three stronger doses weren’t more effective than a placebo in a study of 539 people published in 2015 in the Journal of Allergy and Clinical Immunology. 

Merck funded the studies because it was looking to bring a decongestant to market, said Dr. Meltzer, who helped conduct research published in 2015 and 2016. Merck declined to comment. 

The University of Florida researchers filed another citizen’s petition in 2015, asking that oral phenylephrine be removed from the market and pointed to the recent research, which the FDA and its advisers requested. 

Physicians and pharmacists say because oral phenylephrine is metabolized in the gut and liver, it can’t reach the bloodstream in sufficient levels and cause the blood vessels to narrow and provide relief.

“The evidence is clear that oral phenylephrine does not work,” said Dr. Hatton. “If it doesn’t get into the blood in the first place, it can’t go to the nose and cause nasal constriction and therefore relieve your congestion.”

Garret FitzGerald, a professor of translational medicine and therapeutics at the Perelman School of Medicine at the University of Pennsylvania who served on the 2007 FDA advisory panel, reviewed the recent studies at the request of The Wall Street Journal, and said the studies and their findings seemed credible. 

Write to Jared S. Hopkins at [email protected]

Citing the findings, doctors, pharmacists and groups including the American Academy of Allergy, Asthma and Immunology and the American College of Clinical Pharmacy have said the pills shouldn’t be sold.

“Why give something if it has no benefit?” said

Eli Meltzer,

an allergist in San Diego who performed some testing. “It’s a waste of money.” 

University of Florida pharmacy researchers who reviewed testing of the pills asked the Food and Drug Administration, in a citizen’s petition filed in 2015, to remove phenylephrine from the list of approved over-the-counter medicines.

The Food and Drug Administration told the researchers in 2016 that it was reviewing the request but was unable to reach a decision because the petition “raises complex issues requiring extensive review and analysis.”

The agency will respond to the researchers, an FDA spokeswoman said, but under federal law, can’t publicly discuss such filings.

Stefanie Ferreri, a professor at the University of North Carolina’s Eshelman School of Pharmacy, who isn’t involved in the petition but has followed the issue, said the FDA is probably not taking action because people face low risk of harm. 

“It’s not a safety concern so it’s not a priority of the FDA,” said Dr. Ferreri, who supports ending phenylephrine’s use in decongestants. 

The Consumer Healthcare Products Association, an industry trade group, said the medicines should remain on the market. The FDA recognized that phenylephrine works safely as an oral decongestant, and its member companies comply with federal regulations, a group spokesman said 

Johnson & Johnson,

which sells Tylenol and Benadryl, said phenylephrine is recognized by the FDA to work safely, and it evaluates the latest science, safety information and regulatory information on all its products. 

Reckitt Benckiser Group

PLC, which makes Mucinex, said it complies with federal regulations in all markets in which it operates.

Haleon

PLC, which makes versions of Theraflu that also contain phenylephrine, declined to comment. 

Phenylephrine is also the main ingredient in injections that increase blood pressure and in topical treatments to relieve hemorrhoids. As a decongestant, studies have found phenylephrine works when given via nasal spray. 

People take decongestant pills to relieve nasal congestion from a cold, flu or allergies. Over-the-counter products that treat cough, sinus and flu symptoms, including phenylephrine pills, generated about $5 billion in sales in 2021, according to the research firm IRI.  

The FDA first permitted use of phenylephrine in 1938. The drug was used in over-the-counter products starting at least in the 1950s. In 1976, the FDA included phenylephrine, along with two other main decongestant ingredients called phenylpropanolamine and pseudoephedrine, as over-the-counter products when it overhauled its regulations.

In 2000, the FDA asked manufacturers to remove phenylpropanolamine over concerns about an association with hemorrhagic stroke. Six years later, Congress restricted sales of products containing pseudoephedrine to behind the pharmacy counter because the ingredient can be used to make methamphetamine. 

Phenylephrine’s use in over-the-counter decongestants increased after use of the other two ingredients was restricted.  

Phenylephrine is now in more than 260 oral nose and sinus medicines, according to a 2020 paper published in JAMA Otolaryngology–Head & Neck Surgery. 

Like many older drugs, phenylephrine didn’t go through the rigorous clinical trials regulators require today for medications.

At least one company tested phenylephrine as a substitute for pseudoephedrine.

Schering-Plough,

which was later acquired by Merck & Co. and at the time made allergy medicine Claritin-D, tested whether swapping in phenylephrine would work. The company found phenylephrine was ineffective, according to published studies, and kept using pseudoephedrine in Claritin-D sold behind a pharmacy counter. 

Bayer AG

now makes Claritin-D, after acquiring it from Merck.

Other companies introduced products with phenylephrine instead of pseudoephedrine, however.

Leslie Hendeles and Randy Hatton, professors at the University of Florida pharmacy school who reviewed research on phenylephrine drugs in the 2000s, said they found insufficient evidence supporting phenylephrine effectiveness. 

In 2007, they first petitioned the FDA to review whether a 10 milligram phenylephrine pill was effective. Experts advising the agency voted, later that year, that the dosage may be effective, but more study was needed.

Since then, researchers have published at least four randomly-controlled studies. All found that phenylephrine wasn’t more effective at relieving congestion than placebo. Schering and then Merck funded the studies. 

In one company-sponsored study, researchers found the 10 milligram doses as well as three stronger doses weren’t more effective than a placebo in a study of 539 people published in 2015 in the Journal of Allergy and Clinical Immunology. 

Merck funded the studies because it was looking to bring a decongestant to market, said Dr. Meltzer, who helped conduct research published in 2015 and 2016. Merck declined to comment. 

The University of Florida researchers filed another citizen’s petition in 2015, asking that oral phenylephrine be removed from the market and pointed to the recent research, which the FDA and its advisers requested. 

Physicians and pharmacists say because oral phenylephrine is metabolized in the gut and liver, it can’t reach the bloodstream in sufficient levels and cause the blood vessels to narrow and provide relief.

“The evidence is clear that oral phenylephrine does not work,” said Dr. Hatton. “If it doesn’t get into the blood in the first place, it can’t go to the nose and cause nasal constriction and therefore relieve your congestion.”

Garret FitzGerald, a professor of translational medicine and therapeutics at the Perelman School of Medicine at the University of Pennsylvania who served on the 2007 FDA advisory panel, reviewed the recent studies at the request of The Wall Street Journal, and said the studies and their findings seemed credible. 

Write to Jared S. Hopkins at [email protected]