Around 2005 the Centers for Disease Control and Prevention (CDC) issued an alert instructing doctors to avoid using specific anti-flu compounds such as amantadine and rimantadine during the flu season because amantadine resistance has been increased in one of the influenza A (H3N2) viruses, which were the cause of flu.
This was one of the first important issues warning the world against quick onset of resistance to antiviral agents for the therapy of influenza and for a possible pandemic of the flu.
Such resistance was first described soon after the first anti-flu drug was used already in the early 1960s,.
A high percentage of resistant flu viruses have been detected since (30 to 80 %) after treatment with a pharmaceutical flu-inhibitor (amantadine). Initially, there were only low levels of resistance (1-3%). Since 2003 the incidence increased dramatically in China, due to increased use of over-the-counter amantadine during a SARS epidemic.
During the 2004–2005 influenza season, 70% of the flu-viruses from China and Hong Kong and 15 % of those from the United States and Europe were resistant to the flu inhibitor.
This high frequency of resistance was due to a quick and global spread of flu viruses with a specific mutation. The consequence of the resistance is that amantadine and rimantadine are now ineffective for prophylaxis against and treatment of infections caused by these viruses anymore. In the table below the rise of resistance against amantadine has been depicted: the quick increase in 2005 surprised all.
The value of palmitoylethanolamide
Given the results of many clinical trials in flu and the common cold supporting the safety and efficacy of palmitoylethanolamide and seen in the context of the serious criticism on the efficacy and safety of oseltamivir and zanamivir, PEA should be reconsidered by clinicians as a new treatment modality for the flu and respiratory infections due to its documented efficacy and more importantly its very benign side effect profile. Furthermore, oseltamivir and zanamivir are known to induce resistance; PEA has a very low likelihood of inducing resistance due to its mechanism of action. Finally, the ease of application of PEA offers the possibility to have a quick therapeutic answer ready in case of a flu epidemic, especially in cases of a mismatch between circulating strains and the recommendations from WHO.