Annual influenza cases exceed one billion worldwide, with the vast majority of patients experiencing mild to moderate severity of illness. This massive health burden explains the extensive research into antivirals, including oseltamivir (Tamiflu). Initial studies supported the utility of oseltamivir for preventing complications, hospitalization and shortening disease course in patients with mild to moderate influenza. However, subsequent analysis determined that Roche (the manufacturer of oseltamivir), purposefully hid data from reviewers, biasing the initial interpretations (Krumholz 2014, Fremantle 2014). Subsequent analysis of the full set of data tempered expected benefits (Jefferson 2014).
Oseltamivir has been consistently found to reduce time to first alleviation of symptoms by approximately 16 hours in adults and 30 hours in children (Jefferson 2014). While earlier alleviation (even if less than a full day) is promising, the trade-off is an increase in side effects, including nausea (NNH = 28), vomiting (NNH = 22), headaches (NNH = 32) and neuropsychiatric effects (NNH = 94). No differences were found in the subsequent development of pneumonia in either kids or adults and no differences were found in subsequent otitis media, bronchitis or sinusitis in kids.
More importantly, none of the available antiviral agents (oseltamivir, zanamivir, baloxivir) have been found to reduce subsequent hospitalization or mortality in nonsevere influenza (Hanula 2024, Gao 2025). Hospitalization is one of the most important outcomes to look at due to the burden on both patients and the healthcare system.
Based on all of the available data, the IDSA recommends treatment with antivirals in the following circumstances: (IDSA Practice Guidelines 2018)
- All patients requiring hospitalization.
- Outpatients of any age with progressive illness, regardless of illness duration
- Outpatients at high-risk for complications including those with chronic medical conditions and immunocompromised patients.
- Children < 2 years of age and adults > 65 years of age.
- Pregnant women and those < 2 weeks postpartum.
Alternatively, chemoprophylaxis with oseltamivir and baloxavir can be beneficial for household contacts. The IDSA recommends consideration for chemoprophylaxis in adults or children who have been in close contact with an influenza patient if the exposure is < 48 hours prior to presentation (IDSA 2018). This recommendation applies to healthcare workers as well. Dosing information can be found here for oseltamivir. Baloxavir data is more recent and its use is not discussed in the 2018 IDSA guidelines. A single weight-based dose was found to reduce the risk of developing influenza in close household contacts by 11% (NNT = 9) (Ikematsu 2020).
