CDC Influenza Antiviral Medications

Neuraminidase Inhibitors

The majority of currently circulating influenza viruses are susceptible to the neuraminidase inhibitor antiviral medications—oseltamivir, zanamivir and peramivir; however, sporadic cases of oseltamivir and peramivir-resistant influenza viruses have been detected worldwide in recent years. Antiviral treatment with a neuraminidase inhibitor is recommended as early as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at greater risk for influenza-related complications.

• Oseltamivir (available as a generic or under the trade name Tamiflu®) is FDA-approved for treatment of influenza in people aged two weeks and older, and for chemoprophylaxis to prevent influenza in people one year of age and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants younger than 14 days old, and for chemoprophylaxis in infants 3 months to 1 year of age, is recommended by the CDC and the American Academy of Pediatrics. If a child is younger than 3 months old, use of oseltamivir for chemoprophylaxis is not recommended unless the situation is judged critical due to limited data in this age group. Generic oseltamivir was approved by the FDA in August 2016 and became available in December 2016.
• Zanamivir (trade name Relenza®) is FDA-approved to treat influenza in people 7 years and older and to prevent influenza in people 5 years and older. It is not recommended for use in people with underlying respiratory disease, including people with asthma.
• Peramivir (trade  name Rapivab®) is FDA-approved to treat flu in people 2 years and older.

Adamantanes

In recent years, widespread adamantane resistance among influenza A(H3N2) virus strains has made this class of medications less useful clinically. In addition, circulating influenza A(H1N1)pdm09 virus strains are resistant to adamantanes. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A virus strains. (These medications are active against influenza A viruses but not influenza B viruses.

• Amantadine (generic) is approved to treat and prevent only influenza A viruses in people older than 1 year.
• Rimantadine (generic or under the trade name Flumadine®) is approved to prevent only influenza A virus infection among people older than 1 year. It is approved to treat only influenza A virus infections in people 17 years and older.

Endonuclease inhibitor

The Food and Drug Administration (FDA) approved a new influenza antiviral drug, baloxavir marboxil (trade name Xofluza®), on October 24, 2018. This website is awaiting updated clinical guidance from the CDC.

FDA Label Information - baloxavir marboxil (Xofluza®)

Indications:  baloxavir marboxilis a polymerase acidic (PA) endonuclease inhibitor indicated for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours.

Limitations of Use: Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance, or changes in viral virulence could diminish the clinical benefit of antiviral drugs.

Mechanism of Action: Viral RNA lacks primer nucleotides necessary to initiate viral mRNA translation by host ribosomes. However, the influenza A virus comes equipped with an endonuclease enzyme that is able to clip and snatch the required primer units from host mRNA and then cap the viral mRNA. Capped viral mRNA is able to initiate translation by host ribosomes to synthesize the viral proteins necessary for viral replication. Baloxavir marboxil inhibits the clip, snatch and cap mechanism. Uncapped viral mRNA, is incapable of utilizing the host ribosomes to produce viral proteins.

Timing of Treatment and Implications for Patient Evaluation, Treatment and Testing

Clinical benefit is greatest when antiviral treatment is administered early in the illness course. When indicated, antiviral treatment should be started as soon as possible after illness onset and should not be delayed even for a few hours to wait for the results of testing. Ideally, treatment should be initiated within 48 hours of symptom onset. However, antiviral treatment initiated later than 48 hours after illness onset can still be beneficial for some patients. Observational studies of hospitalized patients suggest that while the greatest benefit occurs when antiviral treatment is initiated within 48 hours of illness onset, treatment might still be beneficial when initiated up to 4 or 5 days after symptom onset. Also, a randomized placebo controlled study suggested clinical benefit when oseltamivir was initiated 72 hours after illness onset among febrile children with uncomplicated influenza. Clinical judgment, on the basis of
the patient’s disease severity and progression, age, underlying medical conditions, likelihood of influenza, and time since onset of symptoms, is important when making antiviral treatment decisions for outpatients.

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