Meta-analysis suggests oral phenylephrine may be ineffective for nasal congestion as measured by nasal airway resistance

In a systematic review and meta-analysis published in the Annals of Pharmacotherapy, oral phenylephrine was demonstrated to be ineffective for the treatment of nasal congestion as measured by nasal airway resistance (NAR).

Phenylephrine use has notably increased since retailers have been required to keep products that contain pseudoephedrine behind store counters as part of the USA Patriot Act's Combat Methamphetamine Epidemic Act. In addition, a past alternative to pseudoephedrine, phenylpropanolamine, was voluntarily removed from the US market in 2000 following reports of its association with increased hemorrhagic stroke rates.

In this study, the authors conducted a search of MEDLINE, the Cochrane Central Registry of Controlled Trials, EMBASE, International Pharmaceutical Abstracts and the Federal Register to identify studies assessing the efficacy of oral phenylephrine on nasal congestion. Their search yielded 15 randomized, placebo-controlled, single-dose studies involving patients who mostly were suffering from the common cold. The study's primary outcome was the difference in the maximum reduction in NAR from baseline over 2 hours with phenylephrine compared with placebo. The authors also evaluated the effects of phenylephrine on patient-reported nasal congestion symptom relief, as well as on blood pressure, heart rate, and other cardiovascular effects.

Phenylephrine 10 mg failed to significantly decrease NAR compared with placebo (pooled mean difference; 10.1%; 95% CI, –3.8% to –23.9%). A significant benefit was demonstrated, however, in studies that used phenylephrine 15 mg or 25 mg compared with placebo, suggesting a possible dose-effect response (pooled mean differences; 22.6%; 95% CI, 12.4%–32.9% and 27.6%; 95% CI, 17.5%–37.7%, respectively). Eight studies providing subjective assessments of patient response to phenylephrine reported inconsistent results. Oral phenylephrine at doses of ≤25 mg was not found to have a significant effect on heart rate or systolic and diastolic blood pressures.

A potential explanation for the lack of beneficial effect may be the poor oral bioavailability - only 38% - of oral phenylephrine. The authors suggested that a measurable effect on nasal congestion may require higher doses (eg 25 mg) of phenylephrine. They also said that their findings do not justify the use of the FDA-recommended non-prescription dose of oral phenylephrine.

Based upon the results of their analysis, the authors recommended that oral phenylephrine be reclassified as a non-prescription Category III drug (ie, available data are insufficient to classify it as safe and effective; further testing is required). Phenylephrine is currently classified as a non-prescription Category I drug (ie, generally recognized as safe and effective for the claimed therapeutic condition.

The authors suggested that the efficacy of phenylephedrine (measured by NAR) and the safety of the drug be tested in randomized controlled trials using a range of doses to determine whether it should be recommended for nonprescription or prescription use.

SOURCE Hatton RC, Winterstein AG, McKelvey RP, Shuster J, Hendeles L. Efficacy and safety of oral phenylephrine: A systematic review and meta-analysis. Ann Pharmacother. 2007; [original draft published online ahead of print]. Jan 30, 2006. Available at: http://www.theannals.com/,

SOURCE Hatton RC, Winterstein AG, McKelvey RP, Shuster J, Hendeles L. Efficacy and safety of oral phenylephrine: A systematic review and meta-analysis. Ann Pharmacother. 2007; [original draft published online ahead of print]. Jan 30, 2006. Available at: http://www.theannals.com/, doi 10.1345/aph.1H679. Accessed February 15, 2007.