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Choice of antiviral therapy for children with suspected or confirmed influenza[1]

Choice of antiviral therapy for children with suspected or confirmed influenza[1]
Choice of agent according to clinical characteristics
Patient group Preferred agent(s) Alternative agent
Children with severe illness
Any of the following:
  • Hospitalization
  • Serious complications (eg, lower respiratory tract complications, myocarditis, encephalitis)
  • Progressive clinical deterioration
  • Oral oseltamivir*
  • IV peramivir (for those ≥6 months of age)
Children with nonsevere illness
  • Age 2 weeks through 4 years
  • Oral oseltamivir*
  • IV peramivir (for those ≥6 months)
  • Age 5 through 6 years
  • Oral oseltamivir*
  • Oral baloxavir
  • IV peramivir (for those ≥6 months)
  • Age ≥7 years
  • Oral oseltamivir*
  • Inhaled zanamivir
  • Oral baloxavir
  • IV peramivir
  
Considerations in choice of agent in children with nonsevere illness
Agent Advantages Disadvantages
  • Oral oseltamivir*
  • Best-studied agent in children and agent with most clinical experience
  • Greater experience with this agent in patients with severe illness
  • Requires twice per day administration for 5 days
  • Emergence of escape mutants, particularly in immunocompromised patients
  • Adverse effects: Nausea, vomiting, diarrhea, headache
  • Inhaled zanamivir
  • May have shorter time to alleviation of symptoms than other agentsΔ
  • Requires twice per day administration for 5 days
  • Requires inspiratory flow sufficient to mobilize and aerosolize the medication
  • Should be avoided in people with a history of:
    • Underlying lung disease (eg, asthma)
    • Allergy to lactose or milk protein
  • Adverse effects: Sinusitis, dizziness
  • Oral baloxavir
  • Given as a single one-time dose
  • Compared with other agents, may reduce risk of influenza complicationsΔ
  • Compared with oseltamivir, may result in shorter duration of symptomsΔ
  • Appears to reduce duration and amount of viral shedding
  • Emergence of escape mutants◊
  • Adverse effects: Vomiting, diarrhea
  • IV peramivir
  • Given as a single one-time dose
  • Requires IV administration
  • Uncertain efficacy for treating infections due to influenza B virus
  • Adverse effects: Diarrhea, vomiting
Antiviral therapy for influenza should be initiated as soon as possible. It should not be delayed pending results of viral testing, including testing for SARS-CoV-2 virus. The agents listed above are active against influenza A and B. However, clinical trials of peramivir included a limited number of subjects with influenza B virus. Refer to related UpToDate content for dosing information.

IV: intravenous; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; OG: orogastric; NG: nasogastric.

* May be administered via OG or NG tube, although pharmacokinetics may differ from oral administration, resulting in decreased concentrations.

¶ Oseltamivir resistance has been reported among children and immunocompromised patients during treatment with oseltamivir, predominantly among immunocompromised patients with influenza A(H1N1)pdm09 virus infection.

Δ Clinical trials directly comparing the antiviral agents listed above with 1 another in children are generally lacking (with the exception of 2 trials comparing oseltamivir and baloxavir[2,3]). However, in a network meta-analysis that estimated the relative efficacy of different antiviral agents (oseltamivir, zanamivir, peramivir, and baloxavir) based upon indirect comparisons from placebo-controlled and oseltamivir-controlled trials (most trials involved adult patients managed in the outpatient setting), zanamivir therapy was associated with the shortest duration of symptoms and baloxavir therapy was associated with the lowest risk of complications[4]. The certainty of these findings is low. The network meta-analysis did not include one of the trials that compared baloxavir and oseltamivir[3].

◊ Baloxavir has been associated with treatment-emergent resistance, particularly when influenza A(H3N2) viruses were circulating. In clinical trials, escape mutants (virus with mutations with decreased susceptibility to baloxavir) were detected in approximately 15 to 20% of young patients (ie, <12 years old) treated with baloxavir and approximately 5 to 10% of older baloxavir recipients.
References:
  1. Centers for Disease Control and Prevention. Influenza antiviral medications: Summary for clinicians. Available at: https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm (Accessed on October 14, 2021).
  2. Ison MG, Portsmouth S, Yoshida Y, et al. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): A randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis 2020; 20:1204.
  3. Baker J, Block SL, Matharu B, et al. Baloxavir marboxil single-dose treatment in influenza-infected children: A randomized, double-blind, active controlled phase 3 safety and efficacy trial (miniSTONE-2). Pediatr Infect Dis J 2020; 39:700.
  4. Liu JW, Lin SH, Wang LC, et al. Comparison of antiviral agents for seasonal influenza outcomes in healthy adults and children: A systematic review and network meta-analysis. JAMA Netw Open 2021; 4:e2119151.
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