Antiviral regimens for individual benefit in patients with severe influenza
In these guidelines, severe influenza is defined as patients with influenza who require ventilatory or haemodynamic support.
For patients with severe influenza, limited data suggest that antiviral therapy is associated with a shorter duration of hospitalisation. The benefit is greatest when treatment is started within 48 hours of illness onset; however, for patients who require intensive care support, starting treatment after 48 hours of illness onset has been associated with a reduced likelihood of mortalityGao, 2024Xu, 2023Sarda, 2019Health Protection Agency (HPA), 2019World Health Organization (WHO), 2024.
Double-dose regimens of oseltamivir for patients with severe influenza are not required. Randomised controlled trials did not demonstrate clinical or virological benefit and pharmacokinetic studies suggest that standard-dose oseltamivir provides adequate drug exposure in patients with severe influenza, including those receiving renal replacement therapy, extracorporeal membrane oxygenation (ECMO) and patients with obesityHernu, 2018Marty, 2017Rayner, 2013Sarda, 2019.
For patients with severe influenza, useXu, 2023:
oseltamivir orally, 12-hourly for 5 days. For dosage adjustment in adults with kidney impairment, see oseltamivir dosage adjustment oseltamivir oseltamivir oseltamivir
adult: 75 mg
child younger than 1 year: 3 mg/kg
child 1 year or older and less than 15 kg: 30 mg
child 1 year or older and 15 to less than 23 kg: 45 mg
child 1 year or older and 23 to 40 kg: 60 mg
child 1 year or older and more than 40 kg: 75 mg.
The mortality benefit of peramivir is unclearWorld Health Organization (WHO), 2024Gao, 2025. For patients with severe influenza who cannot tolerate or absorb oseltamivir, considerGao, 2024Xu, 2023Fang, 2021Scott, 2018Marty, 2017:
peramivir intravenously, daily for 5 days. For dosage adjustment in adults with kidney impairment, see peramivir dosage adjustment peramivir peramivir peramivir
adult: 600 mg
child 1 month to younger than 3 months1: 8 mg/kg
child 3 months to younger than 6 months: 10 mg/kg
child 6 months or older: 12 mg/kg up to 600 mg.
The optimal duration of antiviral therapy for severe influenza is unknownHealth Protection Agency (HPA), 2019. Consider extending the duration of therapy to 10 days (eg in patients with immune compromise) – seek expert advice.
At the time of writing, there are no data to support the use of baloxavir for patients with severe influenzaGao, 2025.
The following treatment cautions apply for patients with severe influenzaWorld Health Organization (WHO), 2024:
- Do not use inhaled zanamivir because it is minimally absorbed from the respiratory tractHealth Protection Agency (HPA), 2019.
- Do not use combination antiviral therapyHealth Protection Agency (HPA), 2019Kumar, 2022.
- Do not use corticosteroids, macrolide antibiotics or intravenous immunoglobulin (IVIg) unless there is another indication for their useUyeki, 2018.
For patients with severe influenza who do not improve, consider whether the infection is caused by strains resistant to neuraminidase inhibitors (usually oseltamivir) and investigate for other potential causes (eg secondary bacterial infection with Streptococcus pneumoniae or Staphylococcus aureus).
Influenza-associated pulmonary aspergillosis is a rare but severe complication of severe influenza; it can occur in patients without typical risk factors for aspergillosisSarda, 2019Lamoth, 2021Verweij, 2020. For management, see Invasive pulmonary aspergillosis.