section_path: Management/Antivirals
section_name: Antivirals
paragraph_text: Antivirals
  
  Antiviral drugs are primarily used to treat severely ill patients, especially those with compromised immune systems. Antivirals are most effective when started in the first 48 hours after symptoms appear. Later administration may still be beneficial for those who have underlying immune defects, those with more severe symptoms, or those who have a higher risk of developing complications if these individuals are still shedding the virus. Antiviral treatment is also recommended if a person is hospitalized with suspected influenza instead of waiting for test results to return and if symptoms are worsening. Most antiviral drugs against influenza fall into two categories: neuraminidase (NA) inhibitors and M2 inhibitors. Baloxavir marboxil is a notable exception, which targets the endonuclease activity of the viral RNA polymerase and can be used as an alternative to NA and M2 inhibitors for influenza A virus and influenza B virus.
  
  NA inhibitors target the enzymatic activity of NA receptors, mimicking the binding of sialic acid in the active site of NA on influenza A virus and influenza B virus virions so that viral release from infected cells and the rate of viral replication are impaired. NA inhibitors include oseltamivir, which is consumed orally in a prodrug form and converted to its active form in the liver, and zanamivir, which is a powder that is inhaled nasally. Oseltamivir and zanamivir are effective for prophylaxis and post-exposure prophylaxis, and research overall indicates that NA inhibitors are effective at reducing rates of complications, hospitalization, and mortality and the duration of illness. Additionally, the earlier NA inhibitors are provided, the better the outcome, though late administration can still be beneficial in severe cases. Other NA inhibitors include laninamivir and peramivir, the latter of which can be used as an alternative to oseltamivir for people who cannot tolerate or absorb it.
  
  The adamantanes amantadine and rimantadine are orally administered drugs that block the influenza virus' M2 ion channel, preventing viral uncoating. These drugs are only functional against influenza A virus but are no longer recommended for use because of widespread resistance to them among influenza A viruses. Adamantane resistance first emerged in H3N2 in 2003, becoming worldwide by 2008. Oseltamivir resistance is no longer widespread because the 2009 pandemic H1N1 strain (H1N1 pdm09), which is resistant to adamantanes, seemingly replaced resistant strains in circulation. Since the 2009 pandemic, oseltamivir resistance has mainly been observed in patients undergoing therapy, especially the immunocompromised and young children. Oseltamivir resistance is usually reported in H1N1, but has been reported in H3N2 and influenza B viruss less commonly. Because of this, oseltamivir is recommended as the first drug of choice for immunocompetent people, whereas for the immunocompromised, oseltamivir is recommended against H3N2 and influenza B virus and zanamivir against H1N1 pdm09. Zanamivir resistance is observed less frequently, and resistance to peramivir and baloxavir marboxil is possible.