Antiviral Drugs for the Treatment of Suspected or Confirmed Influenza A or Influenza B

Key Messages

What Is the Issue?

• Influenza is a serious viral respiratory infection that can lead to health complications and is among the top causes of death in Canada. Early treatment with antiviral drugs can reduce symptoms and complications.
• Four antivirals are currently authorized by Health Canada for the treatment or prevention of influenza: oseltamivir, zanamivir, peramivir, and baloxavir marboxil. Oseltamivir (oral) and zanamivir (inhaled) are available by prescription and are stockpiled in Canada. Limited amounts of baloxavir marboxil (oral; marketed in March 2025) are available by prescription, and peramivir (IV; approved in January 2017 but not marketed) is available only through Health Canada’s Special Access Program.
• The recommendations for Canada’s antiviral stockpiles were last updated in 2017, before baloxavir marboxil was authorized and without consideration of peramivir. Since then, the WHO has downgraded oseltamivir on its Essential Medicines List and recommends stockpiles include antivirals with different mechanisms of action.
• There are important evidence gaps for the treatment of individuals with nonsevere influenza, and updated comparisons of antiviral efficacy, safety, and resistance are needed. The Public Health Agency of Canada is seeking the assistance of Canada’s Drug Agency to support multijurisdictional decisions on antiviral use for pandemic preparedness.

What Did We Do?

• We identified a recently published systematic review (SR) and network meta-analysis (NMA), referred to as the landmark SR and NMA in our report, and critically appraised it.
• We performed an updated literature search for studies published since the search period defined in the landmark SR and NMA and summarized the results from any new eligible randomized controlled trials.

What Did We Find?

• Our critical appraisal of the landmark SR and NMA found that overall confidence in the results of the SR was high, and the NMA was methodologically strong and produced relevant and credible findings.
• The landmark SR and NMA found that baloxavir marboxil, oseltamivir, peramivir, and zanamivir did not significantly reduce deaths or hospital admissions, and there was no increase in serious side effects compared to standard care or placebo. The antivirals did shorten the duration of influenza symptoms by up to 1 day.
• There were no major differences between the antiviral drugs in comparisons of how well they worked for the same outcomes or for their side effects, even across different patient groups. However, baloxavir marboxil may increase the risk of developing drug-resistant virus strains.
• A newer clinical trial comparing baloxavir marboxil and oseltamivir also found no difference in symptom relief or serious side effects. This study also detected some antiviral resistance following treatment with baloxavir marboxil using a different assessment approach, but not for oseltamivir.
• Neither the landmark SR and NMA nor the updated search conducted on January 9, 2025, found any evidence reporting on study withdrawal due to side effects or on human-to-human transmission of the influenza virus. The lack of data on transmission is a noted limitation of the landmark SR and NMA.

What Does This Mean?

• Decisions on stockpiling antivirals for influenza should consider the efficacy, safety, and potential benefits for populations at high risk for infection, as well as the impact of symptoms on health care resources and the risk of antiviral resistance. While baloxavir marboxil may provide some benefits, its potential for resistance requires careful management.
• A diversified stockpile of antiviral medications, considering logistics and supply, may be warranted instead of reliance on drugs with a single mechanism of action.