Interim Guidance for Clinicians to Prioritize Antiviral Treatment of Influenza in the Setting of Reduced Availability of Oseltamivir

Seasonal influenza activity is high across the United States and currently very high in Idaho. Four FDA approved prescription antiviral medications (oseltamivir, baloxavir, zanamivir, and peramivir) are available for use for early treatment of outpatients with influenza. The clinical benefit of antiviral treatment of influenza is greatest when treatment is started early (within 2 days of illness onset) in people with mild, uncomplicated illness.

While the Food and Drug Administration (FDA) has not indicated shortages of oseltamivir (generic or Tamiflu) in any of its forms (capsules, oral suspension), CDC has received numerous anecdotal reports of availability issues for generic oseltamivir. Clinicians should be prepared to prioritize oseltamivir for treatment and be aware of other influenza antivirals recommended for treating influenza in areas where oseltamivir is temporarily unavailable. Available information suggests that current local antiviral availability issues are due to limited availability of generic oseltamivir, specifically.

General Recommendations for the Prioritization of Antiviral Treatment of Influenza

• 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.
• Antiviral treatment of outpatients should be prioritized for people who test positive for influenza within 2 days of illness onset.
• 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. 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

Use of influenza testing, particularly rapid molecular assays, can inform antiviral treatment decisions, especially when other respiratory viruses are co-circulating in the community. CDC has testing guidance for clinicians when SARS-CoV-2 and influenza viruses are co-circulating.

• 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 suspected influenza, or patients highly suspected to have influenza (e.g., an ill patient who has a household member with laboratory-confirmed influenza).

When Antiviral Supplies are Limited

For hospitalized patients, prioritize oseltamivir treatment as soon as possible for patients with suspected or laboratory-confirmed influenza.

• Oseltamivir is the only antiviral that is recommended for treating influenza in hospitalized patients. Oseltamivir treatment is recommended to be started as soon as possible without waiting for results of influenza testing, such as in the emergency department or in admitted patients with high suspicion for influenza.
• There are limited data for using inhaled zanamivir, intravenous peramivir, or baloxavir for treating influenza in hospitalized patients.
• In a recent clinical trial, the addition of baloxavir to a neuraminidase inhibitor (primarily oseltamivir) did not show clinical benefit compared to neuraminidase inhibitor treatment alone in hospitalized patients with influenza aged 12 years and older.
• 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.

For 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.
• 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.

o  Baloxavir is not recommended for pregnant people or those less than 2 weeks postpartum.

o  Baloxavir is not recommended for treating influenza in immunocompromised people.

o  Treatment with a neuraminidase inhibitor (oseltamivir, zanamivir, or peramivir) is recommended for immunocompromised people with influenza.

For children aged 5 years and older, if generic oseltamivir is unavailable, baloxavir can be used for early treatment of influenza in otherwise healthy children aged 5 years and older, and for children aged 12 years and older with underlying conditions that increase their risk of influenza complications. 

For children less than 5 years of age, oseltamivir is the only recommended oral antiviral for treatment.

• If oseltamivir suspension is unavailable for treating influenza in young children, clinicians can request that pharmacists compound a suspension from oseltamivir capsules. For children who are not able to swallow prescribed oseltamivir capsules, the prescribed capsules may be opened and mixed with a thick sweetened liquid, such as chocolate syrup, prior to administration.

In Institutional Settings when an influenza outbreak is not occurring, prioritize oseltamivir for early treatment of influenza in residents of congregate settings who test positive for influenza.

In Institutional Settings during a laboratory confirmed influenza outbreaks, 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.
• Although baloxavir may be used for treatment, there are no available data on using baloxavir in LTCFs for treatment or post-exposure chemoprophylaxis.

When local generic oseltamivir availability issues are resolved, CDC recommends reverting back to original antiviral recommendations that include clinical diagnosis and empiric antiviral treatment of influenza in outpatients.

Contact Eastern Idaho Public Health at 208-533-3152 with questions or to report influenza clusters or outbreaks.

For More Information

·     CDC. Information for Clinicians on Influenza Virus Testing.

·     CDC. Influenza Antiviral Medications: Summary for Clinicians.

·     CDC. Interim Guidance for Influenza Outbreak Management in Long-Term Care and Post-Acute Care Facilities.

·     CDC. Testing and Management Considerations for Nursing Home Residents with Acute Respiratory Illness Symptoms when SARS-CoV-2 and Influenza Viruses are Co-circulating.