University of Florida pharmacists say a popular decongestant in over-the-counter medications is ineffective at the Food and Drug Administration’s approved dose.

Phenylephrine is making its way into oral cold and allergy medications in response to new federal restrictions on the sale of pseudoephedrine, an industry standard decongestant that can be used to illegally produce methamphetamine.

As the late September deadline to move medications containing pseudoephedrine behind the counter looms, many pharmaceutical companies are reformulating some of their common cold and allergy medications to keep them readily available on store shelves. Most companies are switching to phenylephrine, which cannot be used to make methamphetamine.

But in a peer-reviewed letter to the editor of the Journal of Allergy and Clinical Immunology, UF pharmacists Leslie Hendeles, Pharm.D., and Randy Hatton, Pharm.D., warn that phenylephrine is poorly absorbed into the bloodstream and will not work as well as medications containing pseudoephedrine. Hendeles, an FDA consultant who served on the agency’s pulmonary advisory committee for six years, said the FDA should further investigate the drug as more companies are beginning to use it.

“When it is ingested, it becomes inactivated somewhere between the gut and the liver,” Hendeles said. “More research needs to be done to determine whether higher doses can be effective and safe.”

In 1976, the FDA deemed a 10 milligram oral dose of phenylephrine safe and effective at relieving congestion, making it possible for companies to use the ingredient without conducting studies.
But in their letter, Hendeles and Hatton say phenylephrine does not effectively relieve nasal stuffiness at this dose. They say the FDA cited four tests demonstrating efficacy at the 10 milligram dose, two of which were unpublished and sponsored by drug manufacturers. In contrast, the FDA cited six tests demonstrating no significant difference between phenylephrine and placebo. Hendeles said a higher dose may work, but no research has been published regarding safety at higher doses.

“They need to do a dose-response study to determine at what higher dose they get both efficacy and safety,” Hendeles said.
Susan Johnson, Pharm. D., director of the FDA’s Division of Nonprescription Regulation Development, said once a drug’s ingredients are published in a final monograph, pharmaceutical companies can market it as directed without further FDA approval.

The drug approval process is designed to be public, she added, and citizens have several opportunities to raise questions about new drugs before the agency approves them. The final monograph is not the final word, however. Any individual can issue a citizen’s petition to the FDA asking the agency to reconsider an approval.
“This was all a public process,” Johnson said. “If there are concerns, it was not because the FDA turned a deaf ear.”

Under an amendment to the USA Patriot Act, any medication containing pseudoephedrine will be put under lock and key nationwide by late September. That means consumers will no longer be able to purchase the medicines off the retail shelf but will have to ask store employees for the drugs, show ID and sign a sales log. In addition to the federal regulations, some states, such as Oregon, are enforcing stricter laws requiring prescriptions for drugs containing pseudoephedrine.

Phenylephrine is not new to the market. It has been commonly used in nonprescription nasal sprays and in eye and hemorrhoid medicines for years. In these applications, phenylephrine is highly effective. But Paul Doering, M.S., a University of Florida professor of pharmacy who teaches about over-the-counter medications, said that phenylephrine has rarely been used in oral decongestants, and for good reason.

“As pharmacists we have always avoided this drug,” Doering said. “We all know that it isn’t absorbed into the bloodstream well enough.”
Miles Weinberger, M.D., director of the pediatric allergy and pulmonary division at the University of Iowa College of Medicine, was shocked at the increasing number of companies dropping pseudoephedrine and switching to phenylephrine.

“It’s taking a moderately effective nasal decongestant and replacing it with an ineffective medication,” Weinberger said.
As new drugs flood the market, Hendeles recommends people seeking relief from a cold try a topical nose spray. Sprays with phenylephrine are safe and effective for the relief of nasal stuffiness due to a simple cold lasting less than a week, he said, but the treatments should not be used for stuffiness from allergies lasting longer because a “rebound effect” can actually worsen congestion.

“Consumers should go that extra step and get it (pseudoephedrine) from behind the counter,” Hendeles said.

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