Inhaled Zanamivir vs Oral Oseltamivir on Influenza-Related Hospitalization Risk

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Researchers conducted a study that compared early treatment with inhaled zanamivir vs oral oseltamivir on the risk for hospitalization or death due to influenza infection.

Among nonhospitalized patients at increased risk for complications related to influenza infection, early treatment with inhaled zanamivir was noninferior compared with oral oseltamivir for the prevention of hospitalization or death, according to results of a study published in Clinical Infectious Diseases.

To address the lack of data in regard to the effectiveness of inhaled zanamivir on the risk for hospitalization and death due to influenza infection, researchers in Taiwan performed a nationwide population-based cohort study. The study included nonhospitalized patients with influenza infection who received either inhaled zanamivir or oral oseltamivir within 48 hours of their initial diagnosis. Influenza-related hospitalization or death within 14 days was the primary outcome. Excluded patients included those who met the primary outcome within 2 days of treatment initiation. In addition, Cox proportional regression was used to estimate the adjusted hazard ratios (aHR) of hospitalization or death within 14 days.

Among a total of 865,032 patients included in the analysis, 595,897 (68.9%) received inhaled zanamivir and 269,135 (31.1%) received oral oseltamivir. No differences were observed in regard to the risk for hospitalization or death between patients who received inhaled zanamivir vs oral oseltamivir (aHR, 1.01; 95% CI, 0.96-1.06). In addition, outcomes of zanamivir treatment were noninferior compared with oral oseltamivir among 2 subgroups of high-risk patients, including those aged 65 and older (aHR, 1.14; 95% CI, 1.05-1.25) and those with chronic lung disease (aHR, 1.23; 95% CI, 1.08-1.41).

Study limitations included the lack of access to laboratory findings, including molecular assays and rapid influenza diagnostic testing, and that the results are not generalizable to patients with severe influenza infection. In addition, data on medication adherence, influenza vaccination status, bacterial coinfection, and severity of influenza infection were not included.

The researchers concluded, “This finding strongly supports the innovative strategy which uses inhaled zanamivir as the first-line antiviral drug for the majority of outpatients to minimize the risk for emergence of resistance to oseltamivir, while reserving oseltamivir (and peramivir) for hospitalized patients with severe, complicated diseases which require [effective] systemic bioavailability to maximize the success rate of antiviral treatment.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Su C-P, Chan KA, Huang C-T, Fang C-T. Inhaled zanamivir versus oral oseltamivir to prevent influenza-related hospitalization or death: a nationwide population-based quasi-experimental study. Clin Infect Dis. Published online March 17, 2022. doi: 10.1093/cid/ciac217