In early November, two University of Florida professors submitted a citizen petition to FDA requesting that phenylephrine be removed from the OTC monograph and thereby taken off the OTC market because it lacks efficacy in relieving nasal congestion.

“Data from several studies clearly demonstrate that when taken orally, phenylephrine doesn’t relieve nasal congestion,” Leslie Hendeles, PharmD, professor of pharmacotherapy and translational research at University of Florida (UF) College of Pharmacy and professor of pediatrics (pulmonary) at UF College of Medicine, told Pharmacy Today.

“FDA will likely convene an OTC/pulmonary/allergy advisory committee meeting to deliberate our request, but the Consumer Healthcare Products Association will likely oppose our petition,” said Hendeles.

What do the data show?

Because phenylephrine is almost completely inactivated in the gut and during the first pass through the liver, little of the drug gets into the blood. Double-blind studies, discussed in the petition, show that even at four times the FDA-approved dose (i.e., 40 mg), phenylephrine is no more effective than placebo in relieving stuffiness. Some of the study results are summarized here, but additional data can be found in the petition.

Specific results include those from a multicenter, Phase II parallel trial among 539 adults with seasonal allergic rhinitis in which participants were treated with either phenylephrine 10-mg tablets at fixed doses of 10, 20, 30, or 40 mg or with placebo for 7 days.1 No difference was found between groups in the mean change from baseline to the end of the study period in daily reflective nasal congestion score.

In addition, data from a three-way crossover, placebo-controlled study of the nasal decongestant effect of single doses of phenylephrine 12 mg, pseudoephedrine 60 mg, or placebo among 39 grass-sensitive adults exposed to grass pollen in the Vienna Challenge Chamber showed that phenylephrine was not significantly different from placebo in the mean change in subjective nasal congestion scores.2 Significant improvements in congestion were seen with pseudoephedrine compared with phenylephrine and placebo.

How did it get approved in the first place?

The approval of phenylephrine many years ago is an interesting story, according to Randy Hatton, PharmD, FCCP, BCPS, clinical professor of pharmacotherapy and translational research at the UF College of Pharmacy.

“Phenylephrine was discovered and patented in 1927 as an analogue to adrenaline,” Hatton told Today. “Like all OTC products, it was approved by the FDA’s monograph system. If an ingredient in an OTC product is included in the monograph, it can be marketed. At the time that the monographs were established back in the 1970s, it was an attempt to review a massive amount of data on safety and efficacy of existing OTC drugs,” he said. “Much of the data reviewed by the OTC review panels was older data that often would not meet today’s standards for good evidence. In the case of phenylephrine, most of the data were unpublished data.”

Clinical implications

If phenylephrine does not work or is removed from the OTC market in the future, patients and clinicians need alternative options. “For nasal stuffiness due to a cold, the most rapid and effective relief can be obtained from an OTC topical nasal decongestant such as oxymetazoline,” Hendeles told Today. “However, such drugs should not be used to relieve nasal congestion associated with allergic rhinitis since they can cause rebound congestion if used for more than 3 days. For allergic rhinitis, an OTC intranasal steroid would be most effective, such as fluticasone or triamcinolone.”

Hendeles continued, “For sinus congestion or eustachian tube dysfunction, as well as colds and allergic rhinitis, patients over 18 years of age can still obtain pseudoephedrine without a prescription from behind the counter [i.e., show a photo identification, and the purchase is entered into a database].” He added, “However, oral pseudoephedrine is less effective than topical therapy for colds and allergic rhinitis. It is noteworthy, however, that phenylephrine is an effective alpha adrenergic stimulant when given I.V. during surgery for dropping blood pressure and when applied topically to the nose or eyes, as these routes bypass the presystemic clearance.”

“Phenylephrine will not help patients and will ultimately be a waste of money for them,” Hendeles concluded. “Patients deserve a safe and effective medication when they need relief! We are therefore petitioning FDA to remove it from the marketplace.”

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