Influenza Outcomes Mixed With Combination Antivirals

Although a combination of amantadine, oseltamivir, and ribavirin was associated with a reduction in viral load in influenza, the treatment was not associated with any clinical improvements compared with oseltamivir monotherapy, according to the results of a recent study.

Preclinical data has indicated that a combination of antivirals could help to improve outcomes among influenza patients. To explore this option, researchers conducted a randomized, double-blind, multicenter phase 2 trial of oseltamivir, amantadine, and ribavirin compared with oseltamivir monotherapy with matching placebo. All participants were aged 18 years or older, had influenza, and were at increased risk of complications. They were randomly assigned to receive either oseltamivir (75 mg), amantadine (100 mg), and ribavirin (600 mg) combination therapy or oseltamivir monotherapy twice daily for 5 days.
__________________________________________________________________

The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction (PCR) in nasopharyngeal swab at day 3.

Overall, 80 of the 200 participants in the combination group had detectable virus at day 3 compared with 97 of the 194 participants in the monotherapy group. No benefit was observed in multiple secondary endpoints, including median duration of symptoms (4.5 days in the combination group and 4.0 days in the monotherapy group).

The most common adverse events were gastrointestinal-related disorders, including nausea (12% in the combination group vs 11% in the monotherapy groups), diarrhea (10% in the combination group vs 11% in the monotherapy group), and vomiting (7% in the combination group and 4% in the monotherapy group).

“Although combination treatment showed a significant decrease in viral shedding at day 3 relative to monotherapy, this difference was not associated with improved clinical benefit. More work is needed to understand why there was no clinical benefit when a difference in virological outcome was identified.”

—Michael Potts

Reference:

Beigel JH, Bao Y, Beeler J, et al. Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial [published online September 22, 2017]. doi: http://dx.doi.org/10.1016/S1473-3099(17)30476-0.