By Francesca Lunzer Kritz
Special to The Washington Post
Tuesday, September 26, 2006
It could be a tough fall allergy season, and not just because of the ragweed count. Another problem, say some experts, is an ingredient many drug companies have begun putting in nonprescription decongestants in place of pseudoephedrine.
The active ingredient in Sudafed and other oral decongestants, pseudoephedrine will be subject to new federal sales restrictions starting Saturday. Officials hope the limits -- which require that all pseudoephedrine products be kept behind store counters or in locked cases and that buyers show an ID and have their purchases logged and limited to a few each month -- will curb illegal production of crystal methamphetamine, an addictive drug that is commonly made with pseudoephedrine.
But decongestant manufacturers aren't willing to gamble that millions of people with allergies and colds -- who together spend more than $400 million a year on oral decongestants -- will put up with such inconveniences at the sales counter. So drug companies have been taking the pseudoephedrine out of many over-the-counter products and replacing it with an older ingredient, phenylephrine.
Call it a step up for phenylephrine, which previously had been relegated mostly to shorter-acting decongestant nasal sprays, such as some Neo-Synephrine and Vicks Sinex products.
Phenylephrine had been on the market for decades when the Food and Drug Administration in 1972 reviewed all nonprescription ingredients being sold. An agency review panel published a report in 1976 classifying the drug as "generally recognized as safe and effective" at a 10 milligram dose without calling for any new studies.
But phenylephrine may not have the punch of the star performer it is replacing. Writing in a prominent allergy journal, two University of Florida research pharmacists recently questioned the effectiveness of the 10 mg dose and the clinical evidence offered in support of the review panel's decision.
In their peer-reviewed letter, published in July in the Journal of Allergy and Clinical Immunology, Leslie Hendeles and Randy Hatton report they were able to track down 11 of the 13 phenylephrine studies -- most of them unpublished -- that the panel reviewed. Of these 11, they found, only four showed the drug to be effective at the 10 mg dose.
After submitting the letter, Hendeles and Hatton found four additional studies. Two, Hendeles says, showed the drug ineffective at the 10 mg dose, one showed borderline effectiveness, and one showed effectiveness at 25 mg, but not at 10.
Rep. Henry Waxman (D-Calif.) the ranking minority member of the House Committee on Government Reform, has asked acting Food and Drug Administration (FDA) commissioner Andrew von Eschenbach to decide whether new studies are needed. The FDA's response, for now, is no, because, according to David W. Boyer, the agency's commissioner for legislation, the FDA is not aware of any data that refute the 1976 report.
The Consumer Healthcare Products Association (CHPA), which represents nonprescription drug manufacturers, has issued a statement defending phenylephrine's effectiveness. "No new data has been presented that disputes FDA's conclusion," wrote the group.
But some experts say data published since the '70s on phenylephrine do raise relevant questions. Some of this data concerns phenylephrine's effect on blood pressure.
Phenylephrine was first marketed as a drug to treat low blood pressure, which it does in the same way it relieves nasal congestion, by constricting blood vessels. A 1988 review article in Medical Toxicology found it would take at least 45 mg of oral phenylephrine to begin to raise blood pressure, an indication of the dose at which the drug starts working.
And a 1982 study in the European Journal of Clinical Pharmacology found that only 38 percent of a phenylephrine dose gets into the bloodstream. William Barr, head of the Center for Clinical Drug Studies at Virginia Commonwealth University, in Richmond, and other researchers say enzymes inactivate much of the phenylephrine dose in the gut, before it reaches the bloodstream from where it travels to the nasal passages -- suggesting a larger dose may be needed to be effective. Pseudoephedrine reaches the bloodstream at about 90 percent of its original strength.
Linda Suydam, president of CHPA, says that with many drugs, a far lower percentage of a given dose than 90 percent is sufficient to be effective.
Questions about phenylephrine's effectiveness stand to affect not only allergy sufferers. Many airline passengers use pseudoephedrine to fend off ear pain when a flight starts its descent. "Ten thousand feet and dropping is no time to find out phenylephrine doesn't work for you," says David Eisenman, an assistant professor at the University of Maryland School of Medicine, who specializes in conditions of the ear.
Meanwhile, other experts have weighed in.
Richard Herrier, a professor of pharmacy practice at the University of Arizona, and Rohit Katial, program director of allergy and immunology at the National Jewish Medical and Research Center in Denver, reviewed the sources cited by Hendeles and Hatton and concluded that the data do not show phenylephrine to be effective at the 10 mg dose. Editors of the 2006 edition of Drug Information, a professional resource published by the American Society of Health-System Pharmacists, were "not able to answer the question as to whether it's as safe and effective as pseudoephedrine," based on published medical literature, according to associate editor Elaine Snow.
Results are due shortly from a 36-patient study testing a 12 mg dose of phenylephrine against pseudoephedrine and placebo. The study was funded by Schering-Plough, which for now has replaced pseudoephedrine in only one decongestant product: a Coricidin version. It has left pseudoephedrine in its Claritin-D (for decongestant) line. One likely reason: Phenylephrine is not available in a long-acting formulation -- it must be taken every four hours for continued effectiveness, according to its label -- while pseudoephedrine is sold in four-to-six-hour, 12-hour and even 24-hour versions.
Erica Jones, a spokeswoman for Pfizer, maker of Sudafed and the newer Sudafed PE (for phenylephrine), says the company has seen repeat sales of the newer product, indicating satisfied customers. But some health-care professionals say they have been getting customer complaints.
"Almost without exception [patients] say, 'I want my Sudafed back,' " says Eric Schenkel, an assistant professor of medicine at the Hahnemann School of Medicine in Philadelphia and director of Valley Allergy and Asthma Treatment Center in Easton, Pa.
And a Web information page about Vicks's reformulated decongestant DayQuil ( http://vicks.com/pseudoephederine_faq.shtml ) includes this comment, which DayQuil spokesman Ashoke Mitra says customers have left on the company's consumer hotline: "The new version of DayQuil doesn't work as well for me as the old version."
(The reply posted by the company: "We replaced the decongestant pseudoephedrine, used in the old version of DayQuil, with the decongestant phenylephrine in the new version. Both decongestants have been approved by the FDA and are considered safe and effective when used as directed.")
Patients with stuffy noses who are dissatisfied with phenylephrine and unwilling to put up with the inconvenience of buying pseudoephedrine after Sept. 30, may want to try nasal saline spray, which is available at all pharmacies, suggests Larry Sasich, a consulting pharmacist to Washington-based advocacy group Public Citizen. Nasal decongestant sprays are another alternative, says Schenkel, who advises people to limit use to three days or risk making their symptoms worse. Allergy-caused stuffy noses may respond better to nasal steroid sprays such as Nasonex or Flonase, available only by prescription.
But don't expect pseudoephedrine to go back to being an easy sell. Although only a small percentage of crystal methamphetamine is made with pseudoephedrine pirated from over-the-counter drugs, according to the Drug Enforcement Administration, use of the illegal drug is far lower in states that restrict pseudoephedrine sales to drugstores only than elsewhere. While only a few states, none of them in the Washington area, have that restriction, Congress could also impose this limit. ·
Francesca Lunzer Kritz is a Washington-area freelance health care writer. Comments:email@example.com.