Double dose of oseltamivir had no advantage in severe influenza
Taking a second dose of oseltamivir for 5 days did not have a clinical or virological effect on patients with severe influenza, according to recent findings by the South East Asia Infectious Disease Clinical Research Network.
“Higher oseltamivir doses were tested in patients with uncomplicated influenza, but no consistently improved clinical or virological outcomes were found compared with the standard dose,” the researchers wrote in the British Medical Journal. “Despite a lack of evidence, several authorities have suggested use of double-dose oseltamivir for severe influenza.”
The researchers conducted a double blind, randomized trial in 13 hospitals throughout Indonesia, Singapore, Thailand and Vietnam. Patients were randomly assigned to the standard dose of oseltamivir (Tamiflu, Genentech) or a double dose. For adults, the standard dose is 75 mg, twice daily, for 5 days. The children in the study received the pediatric equivalent.
The study included 326 patients, including 246 children. Most patients (79.8%) had influenza A and 3.9% were false positive by rapid antigen testing. On day 5 of treatment, 72.3% of patients who received the double dose were negative by RT-PCR compared with 68.2% who received the standard dose (P=.42). In children, the rates were 71% for the double dose and 67% for the standard dose (P=.52). There were no differences in viral clearance according to virus type, age or duration of illness before randomization.
Sixteen patients in the double-dose group and 20 patients in the standard-dose group met the criteria for clinical failure on day 5 (P=.44), and were given an additional 5 days of oseltamivir. There was no difference in mortality between the two doses.
“This trial examined an important clinical and public health question and showed a lack of a clinical or virological benefit of double dose compared with standard dose oseltamivir,” the researchers wrote. “Our results and other observational reports do not support routine use of double dose oseltamivir to treat severe influenza. These findings have implications for both clinical management and pandemic preparedness, including during the current H7N9 epidemic.”
Disclosure: The researchers report financial relationships with AIMM Therapeutics, AstraZeneca, AVI BioPharma, BioCryst, Crucell BV, Fabentech, GlaxoSmithKline, Inviragen, MediVector, MSD, NexBio, Roche, Romark, Sanofi-Pasteur, 3M and Theraclone.