Interim guidance for clinicians to prioritize antiviral treatment of influenza in the setting of reduced availability of Oseltamivir

Actions requested

• Be aware of possible shortages of influenza antivirals including oseltamivir (Tamiflu) while influenza and other respiratory viral activity remains elevated.
  • Per the Centers for Disease Control and Prevention (CDC), available information suggests that current local antiviral availability issues are due to limited availability of generic, oseltamivir, specifically.
• Recommend influenza vaccination for all individuals aged 6 months or older as primary prevention against influenza virus infection.
• Review the general recommendations and prioritization guidance when antiviral supplies are limited:

General recommendations:

• If available, brand-name oseltamivir (Tamiflu®) can be used to treat outpatients and hospitalized patients with influenza.
  
• If oseltamivir is unavailable, oral baloxavir, inhaled zanamivir, or intravenous peramivir can be used for early treatment of outpatients at increased risk for complications who present with uncomplicated influenza, depending upon age and contraindications.
  
• When there is limited availability of oseltamivir or other antivirals, antiviral treatment should target patients with influenza who are at the highest risk of severe disease and those who are hospitalized.
  
• Antiviral treatment of outpatients should be prioritized for persons who test positive for influenza within 2 days of illness onset.
  
• When there is limited availability of oseltamivir or other antivirals, patients with clinically mild influenza who are otherwise healthy and not at increased risk of influenza complications can be managed with supportive care without antiviral treatment.

Influenza testing considerations

• When antivirals are available, a clinical diagnosis of influenza without influenza testing can be made to support prescribing empiric antiviral treatment in outpatients.
  
• However, in settings where oseltamivir is currently unavailable, influenza testing for patients with suspected influenza is highly recommended to guide antiviral treatment
  
• When there are limited supplies of antivirals, treatment of suspected influenza without a positive test result should be limited to those who are being hospitalized with influenza, or patients highly suspected to have influenza (e.g., an ill patient who has a household member with laboratory-confirmed influenza)

Guidance for prioritization when antiviral supplies are limited

Hospitalized patients

• Prioritize oseltamivir treatment as soon as possible for hospitalized patients with suspected or laboratory-confirmed influenza.
  • Oseltamivir is the only antiviral that is recommended for treating influenza in hospitalized patients.
    
  • There are limited data for using inhaled zanamivir, intravenous peramivir, or baloxavir for treating influenza in hospitalized patients.
    • Consideration of these influenza antiviral treatments may be done in coordination with an infectious disease consult where available.

Outpatients

Among outpatients, prioritize antiviral treatment for patients who test positive for influenza as follows:

• Patients at increased risk of influenza complications and who test positive for influenza within 2
  days of illness onset.
  
  • People with multiple conditions that place them at increased risk for complications from influenza (e.g., several co-morbidities, age <2 years, and 65 years and older) and those with severe uncontrolled chronic disease might be at highest risk of influenza complications.
    
• Patients who have progressive or severe influenza not requiring hospitalization, even if they test positive for influenza more than 2 days from illness onset.
  
• Patients who are pregnant, less than 2 weeks postpartum or immunocompromised.
  
  • Substantial data from observational studies indicate that oseltamivir treatment of influenza is safe in pregnancy.
    
  • There are no data on the safety or efficacy of baloxavir in pregnancy and baloxavir is not recommended for pregnant people or those less than 2 weeks postpartum.
    
  • Treatment with a neuraminidase inhibitor (oseltamivir, zanamivir, or peramivir) is recommended for immunocompromised people with influenza.
    
  • Baloxavir is not recommended for treating influenza in immunocompromised people because the optimal duration of treatment is unknown and there is concern for emergence of influenza viruses resistant to baloxavir during or after treatment.
    
• Children less than 5 years of age
  
  • Oseltamivir is the only recommended oral antiviral treatment of influenza in children less than 5 years of age.
    
  • If oseltamivir suspension is unavailable for treating influenza in young children, clinicians can request that pharmacist compound a suspension from oseltamivir capsules or consider opening capsules and mixing with a thick sweetened liquid. Attention should be paid to ensure appropriate weight-based dosing.

Institutional settings

• When an influenza outbreak is not occurring, prioritize oseltamivir for early treatment of influenza in residents of congregate settings such as long-term care facilities (LTCFs), who test positive for influenza
  
• In the setting of laboratory-confirmed influenza outbreaks in LTCFs:
  
  • Early empiric antiviral treatment of suspected influenza in residents is recommended. Once an influenza diagnosis is confirmed through testing, post-exposure antiviral chemoprophylaxis of exposed residents is recommended.
    
  • Because institutional outbreaks can be prolonged, consider using a limited duration treatment dosage (twice daily for 5 days) for post-exposure oseltamivir instead of extended use of oseltamivir chemoprophylaxis (once daily), with ongoing active daily monitoring and influenza testing for all residents with new illness signs and symptoms.
    
  • If oseltamivir is not available, baloxavir, zanamivir or peramivir may be used for treatment of influenza.
    
  • Although baloxavir may be used for treatment, there are no available data on using baloxavir in LTCFs for treatment or post-exposure chemoprophylaxis.

Other considerations

In hospitalized patients, oseltamivir can be administered orally or enterically via oro- or nasogastric tube. For hospitalized patients who cannot absorb enterically-administered oseltamivir (e.g., due to gastric stasis, malabsorption, or gastrointestinal bleeding), or when oseltamivir is not available, intravenous peramivir is an option.