Comparing Phenylephrine and Pseudoephedrine: Understanding the Distinctions between the Two Decongestants

Phenylephrine—the chief ingredient in many over-the-counter decongestants—doesn't work, a Food and Drug Administration (FDA) advisory panel concluded earlier this month. 

The committee found that oral medications containing the ingredient are ineffective, but the decision didn’t apply to nasal sprays that include the compound. 

More than 240 FDA-approved products contain phenylephrine, which together grossed almost $1.8 billion last year, the committee said in a statement. Some of the more popular medications include Sudafed PE, some Nyquil products, and Advil congestion.

You may still be able to find oral phenylephrine on drugstore shelves—the advisory committee’s decision isn’t binding, and the FDA is still reviewing the evidence. 

But in the meantime, here’s what you need to know about how phenylephrine became a go-to drug, what went into the committee’s decision, and whether it’s okay to rely on a different but similar-sounding decongestant—pseudoephedrine—if you have a cold.

Phenylephrine is a medication used to relieve nasal discomfort and sinus congestion or pressure—this puts it in a class of drugs called nasal decongestants.

Medications containing phenylephrine come in liquid or tablet form; a phenylephrine nasal spray is also available. The drug works by reducing the swelling of blood vessels in the nasal passages, in order to make breathing out of your nose easier when you're dealing with a cold or allergies.

Pseudoephedrine is also a nasal decongestant and works the same way that phenylephrine does: by relieving sinus congestion and pressure due to colds or allergies.

The key differences between phenylephrine and pseudoephedrine lie in their efficacy, side effects, and potential for abuse.

Medications containing phenylephrine were an answer to people abusing pseudoephedrine, which can be used to make methamphetamine, a synthetic stimulant drug. When Congress passed the Combat Methamphetamine Epidemic Act of 2005, pseudoephedrine remained over-the-counter, but moved behind the pharmacy counter to limit access.

“There was a need to find another option that could be available over-the-counter without the additional effort on behalf of the patient, buying it from the pharmacy and having it monitored over time,” Sterling Elliott, PharmD, a clinical pharmacist and assistant professor of orthopedic surgery at the Northwestern University Feinberg School of Medicine, told Health.

That option was phenylephrine—but it didn't take long for researchers to question the drug's effectiveness.

In 2007 paper, a team of researchers reviewed eight unpublished studies and found that phenylephrine didn’t appear to work any better as a decongestant than a placebo.

The study prompted the FDA to review the compound’s efficacy. Still, using different research, it ultimately found that phenylephrine could clear up congestion. 

“The studies back then were not well designed and had methodological problems and would not be accepted today,” Leslie Hendeles, PharmD, an author of the 2007 study and professor emeritus at the University of Florida College of Pharmacy, told Health. “The panel then did not realize the problems.”

In a 2015 paper, researchers urged the FDA to reevaluate phenylephrine—and it finally did.

In its final statement released this month, the FDA advisory committee said it reviewed five studies conducted over the last decade and unanimously concluded that oral phenylephrine does not affect congestion.

“The oral form may just not be absorbed well enough, and you won’t have high enough concentration in those blood vessels in and around the sinuses to relieve congestion,” Dr. Elliot said. “That’s long been a concern.”

In a statement, the FDA said that it’s reviewing the evidence and hasn’t decided on the status of oral phenylephrine. If the FDA revokes the drug’s over-the-counter designation as GRAS/E (generally recognized as safe and effective), stores may have to remove the medications.

The FDA committee’s statement comes as the United States is entering cold and flu season, leaving people unclear about their options when shopping for decongestants. 

But there’s good news: Pseudoephedrine works in the same way as phenylephrine—by reducing blood vessel swelling in nasal passages—and evidence shows it’s effective when taken by mouth, said Elliot. 

“For pharmacists, for physicians, pseudoephedrine is really the go-to recommendation,” he said. “But obviously, it comes with those additional regulations which have grown out of the concern for abuse.”

Brand names that contain pseudoephedrine include Sudafed and Dimetapp Elixir and it’s widely available as a generic medicine. While you don’t need a prescription for these drugs, you can’t buy them in large quantities.

“It is a good idea to buy the pseudoephedrine products you think your family will need ahead of time,” Dr. Elliot said. “Having these items on hand will save you from a middle-of-the-night run to the pharmacy.”

However, “while pseudoephedrine is an excellent decongestant, it is not right for everybody and every type of congestion,” Dr. Elliot acknowledged.

For example, congestion caused by mucus build-up may require an expectorant to break it up, he said.

“Nasal decongestant sprays are also very effective for treating congestion but are not a good choice for congestion that lasts for more than a few days,” added Engle.

Using sprays for too long or too often can cause the spray to stop working, a phenomenon called rebound congestion.

Hendeles said the most effective medication for allergy-related congestion is usually a nasal steroid such as Flonase. “For both colds and allergies, the most effective medications are delivered by nasal spray,” he added.

If you’re confused about which product is best for you, Dr. Elliot recommended asking a doctor or pharmacist. “You can get an idea of what’s really causing the congestion,” he said, “and pick the right medication to treat it.”