FDA Decides Oral Drugs Containing Phenylephrine are Ineffective for Nasal Congestion Relief
After extensive studies, clinical trials, and appeals, the Food and Drug Administration (FDA) recently declared oral drugs containing phenylephrine as ineffective in relieving nasal congestion caused by colds and flu. These drugs have been sold for almost twenty years in the United States, as well as in Europe and Italy.
The FDA’s decision has raised concerns about the fate of these widely used drugs, which have generated approximately $1.7 billion in annual sales in recent years. In Italy alone, an estimated 3.5 to 4 million packs of phenylephrine-based oral decongestants were sold in 2022.
Phenylephrine was initially approved by the FDA in the mid-1970s but gained popularity in nasal decongestant drugs after the limitations imposed on the use of pseudoephedrine, a proven molecule for reducing nasal congestion. The restrictions on pseudoephedrine were implemented to combat the illegal production of substances like methamphetamines. Pharmaceutical companies turned to phenylephrine as an alternative, despite existing doubts about its effectiveness as an oral decongestant.
Customers who used phenylephrine-based decongestants reported little to no relief from their congestion symptoms, prompting concerns about the efficacy of the drug. Randy Hatton, now a professor of pharmacy at the University of Florida, requested documentation from the FDA regarding the approval process of phenylephrine in the 1970s. Analysis of the material revealed that several studies reporting positive results were conducted by the same research center, raising doubts about the reliability of those findings.
In 2007, Hatton and colleagues filed a petition with the FDA to review the dosage of phenylephrine to determine if higher doses would yield better results. The FDA formed a new working group to investigate the matter, which presented disappointing data provided by a pharmaceutical company that intended to use phenylephrine in its allergy product. The data showed that a significant portion of phenylephrine is broken down in the digestive system, resulting in negligible amounts of the active ingredient reaching the nasal mucosa.
Despite these findings, the FDA did not make any definitive decisions regarding the use of phenylephrine for oral decongestion. The agency allowed the continued sale of drugs containing phenylephrine but requested further studies to assess the potential effectiveness of higher dosage levels.
Merck, a pharmaceutical company interested in researching allergy treatments, conducted two clinical trials in 2015 and 2016. Despite significantly increasing the dosage of phenylephrine, the trials failed to find any reduction in nasal congestion.
Following the publication of these studies, Hatton and colleagues submitted a new petition to the FDA, which led to the recent findings by the agency’s working group. All sixteen members of the group voted in favor of declaring phenylephrine as ineffective, although the decision is non-binding.
The FDA will determine its course of action in the next few months based on these findings. Experts believe that more decisive actions will be taken compared to previous regulatory decisions.
The FDA’s decisions may also have implications in the European Union, where the European Medicines Agency and national agencies regulate medicines. Decongestant products containing phenylephrine, as well as other active ingredients like paracetamol and non-steroidal anti-inflammatories, are sold in the EU. However, the mild decongestant effects of these products are not linked to phenylephrine.
Unlike the US, pseudoephedrine-based drugs are more readily available in the European Union. However, the EMA launched a review earlier this year due to a few cases linking pseudoephedrine to certain cerebral blood vessel pathologies. The evaluation process is ongoing, and potential new rules and limitations will be implemented by the European Commission based on the review’s outcome.
In summary, the FDA’s recent declaration regarding the inefficacy of phenylephrine-based oral drugs for nasal congestion relief may lead to changes in the availability and usage of these drugs. Further studies and decisions from regulatory bodies in the US and the EU will shape the future of nasal decongestant treatments.