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BACKGROUND:A synergistic effect of combination therapy with favipiravir and oseltamivir has been reported in pre-clinical models of influenza. However, no data are available on the clinical effectiveness of combination therapy in severe influenza. METHODS:Data from two separate prospective studies of influenza adults were used to compare outcomes between combination and oseltamivir monotherapy. Outcomes includes rate of clinical improvement, defined as a decrease of 2 categories on a 7-category ordinal scale, and viral RNA detectability over time. Sub-hazard ratio (sHR) was estimated by Fine and Gray model for competing risks. RESULTS:In total, 40 patients were treated with combination therapy and 128 with oseltamivir alone. Clinical improvement on Day 14 occurred in the combination group was higher than in monotherapy group (62.5% vs 42.2%, p=0.0247). The adjusted sHR for combination therapy was 2.06 (95%CI: 1.3-3.26). The proportion of undetectable viral RNA at day 10 was higher in the combination group than oseltamivir group (67.5% vs 21.9%, p<0.01). No significant differences were observed in mortality or other outcomes. CONCLUSIONS:Favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, and this strategy should be formally evaluated in a randomized controlled trial.

Original publication





The Journal of infectious diseases

Publication Date



Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.


CAP-China Network