Antiviral agents used to treat seasonal influenza shorten the time to alleviation of influenza symptoms (TTAS), according to the findings of a systematic review and network meta-analysis recently published in JAMA Network Open.

The 4 antiviral agents approved by the Food and Drug Administration for the treatment of seasonal influenza include the neuraminidase inhibitors oseltamivir, zanamivir, and peramivir, and the polymerase acidic endonuclease inhibitor, baloxavir marboxil. To evaluate the safety and efficacy in treating seasonal influenza in healthy adults and children, the authors obtained randomized clinical trials evaluating these agents with other active agents or placebo. The main outcomes of the study included TTAS, influenza complications, and adverse events.

The authors identified a total of 26 trials that evaluated antiviral drugs used in both low and high doses in 11,897 patients. Of the total patients, 52.9% (n=6294) were male and the mean (SD) age was 32.5 (16.9) years.

”Of all treatments comparing with placebo in efficacy outcomes, high quality evidence indicated that zanamivir 10mg was associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58 to 0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32 to 0.80) based on moderate-quality evidence,” the study authors reported. Findings also revealed that compared with placebo, baloxavir was associated with the lowest risk of total adverse events (RR, 0.84; 95% CI, 0.74 to 0.96; moderate-quality evidence).

Oseltamivir 75mg was associated with an increased risk of nausea (RR, 1.82; 95% CI, 1.38 to 2.41) and vomiting (RR, 1.88; 95% CI, 1.47 to 2.41) when compared with placebo. Compared with oseltamivir 75mg, nausea occurred less frequently with zanamivir (RR, 0.30; 95% CI, 0.13 to 0.67) and baloxavir (RR, 0.47; 95% CI, 0.30 to 0.72) and vomiting occurred less frequently with peramivir 300mg (RR, 0.32; 95% CI, 0.11 to 0.93).

“These findings suggest that zanamivir may be initiated as soon as possible for patients with influenza-like illness; in those who may be at high risk of developing influenza-related complications, baloxavir should be considered,” the authors concluded.


Liu J, Lin S, Wang L, Chiu H, Lee J. Comparison of antiviral agents for seasonal influenza outcomes in healthy adults and children: A systematic review and network meta-analysis. JAMA Network Open. Published online August 13, 2021. doi: 10.1001/jamanetworkopen.2021.19151.