On September 11, 2023, ACCP President Elizabeth A. Farrington, Pharm.D., BCNSP, BCPS, testified before the FDA Nonprescription Drugs Advisory Committee (NDAC) regarding the Generally Recognized as Safe and Effective (GRASE) status of oral phenylephrine as a nasal decongestant.
ACCP’s testimony, building on the longstanding leadership of ACCP members Leslie Hendeles, Pharm.D., and Randy C. Hatton, Pharm.D., FCCP, helped convince NDAC that orally administered phenylephrine is ineffective as a nasal decongestant and that OTC products containing oral phenylephrine should be removed from the market.
NDAC voted 16-0 that current scientific data do not support that the recommended dosage of orally administered phenylephrine is effective as a nasal decongestant. NDAC also voted against additional studies assessing the pharmacokinetics and clinical efficacy of other phenylephrine doses. Neither the FDA nor the committee raised concerns about safety issues with the use of oral phenylephrine at the recommended dose.
- Click here to read a copy of ACCP’s testimony.
- Click here to view the FDA hearing, including testimony from Drs. Hendeles and Farrington.
- Click here to view a 2015 Citizen’s Petition submitted to the FDA by Drs. Hendeles and Hatton.
Background
In 2005, in response to growing concern that pseudoephedrine was being used to illegally manufacture methamphetamine, Congress passed the Combat Methamphetamine Epidemic Act, which required all retail stores nationwide to keep products containing pseudoephedrine “behind the counter.” Consequently, because phenylephrine cannot be converted to methamphetamine and can be sold without restrictions, the manufacturers of oral decongestants substituted phenylephrine for pseudoephedrine in their OTC products.
Phenylephrine is now a major ingredient in oral OTC products marketed for the treatment of upper respiratory congestion. Although phenylephrine is found in 261 such products,1 published peer-reviewed research has shown no clinically significant decongestant effect in patients with nasal congestion from seasonal allergic rhinitis, even at doses of up to 40 mg – 4 times the FDA-approved OTC dose.2
As articulated in a 2015 citizens’ petition3 led by Drs. Hendeles and Hatton and shown by numerous studies and analyses,2,4,5 oral phenylephrine is ineffective at the doses used in current OTC products available in the United States. As noted, phenylephrine is the most common ingredient in oral OTC products marketed for the treatment of nasal congestion and sinus symptoms. However, because of its poor bioavailability, sufficient phenylephrine concentrations never reach the patient’s systemic circulation. Hence, consumers are regularly purchasing FDA-approved products that clearly don’t work.
Despite evidence that oral phenylephrine is ineffective as a decongestant, the FDA had failed to remove it from the OTC nasal decongestant monograph. The OTC monograph system must assure consumers that all drugs on the market are effective.
Next Steps
Following established FDA rule-making procedures, the agency is expected to submit a regulatory ruling on the status of cough medicine formulas containing oral phenylephrine marketed to treat nasal congestion.
As the FDA initiates the process of submitting a regulatory ruling, ACCP has reached out to congressional offices on Capitol Hill to ensure the committees with jurisdiction over the FDA are appropriately engaged in their oversight duties.
Click here to read the New York Times article “Why the F.D.A. Took So Long to Tackle a Disputed Cold Remedy.”
References
1. McCoul ED. Assessment of pharmacologic ingredients in common over-the-counter sinonasal medications. Otolaryngol Head Neck Surg 2020;146:810-5.
2. Meltzer EO. Ratner PH, McGraw T. Oral phenylephrine HCl for nasal congestion in seasonal allergic rhinitis: a randomized, open-label, placebo controlled study. J Allergy Clin Immunol Pract 2015;3:702-8.
3. Hendeles L, Hatton RC. Citizens’ Petition-2015-P-4131-0001, Requesting a Final Rule Removing Oral Phenylephrine from the Final Rule Removing Oral Phenylephrine from the Final Monograph for OTC Nasal Decongestant Products.
4. Horak F, Zieglmayer P, Zieglmayer R, et al. A placebo-controlled study of the nasal decongestant effect of phenylephrine and pseudoephedrine in the Vienna challenge chamber. Ann Allergy Asthma Immunol 2009;102:116-20.
5. Day JH, Briscoe MP, Ratz JD, et al. Efficacy of loratadine-montelukast on nasal congestion in patients with seasonal allergic rhinitis in an environmental exposure unit. Ann Allergy Asthma Immunol 2009;102:328-38.