COMMENTARY

What's New for Treating Flu? CDC 2019 Antiviral Drug Recommendations

Angela J. Campbell, MD, MPH

Disclosures

January 22, 2019

Editorial Collaboration

Medscape &

An Escalating Flu Burden

The 2018-2019 influenza season is well underway. Laboratory data suggest that influenza A(H1N1)pdm09 viruses are predominating nationwide during this flu season, with the exception of the Southeastern part of the country, which is seeing mostly influenza A(H3N2) viruses. While current severity is lower than it was during the 2017-2018 flu season at this time, flu is still taking a serious toll.

Unfortunately, every season we know that flu can cause such serious complications as pneumonia and inflammation of nonrespiratory organs (heart, brain) and muscle. An extreme inflammatory response can lead to sepsis, multiorgan failure, and even death. These complications can occur from influenza virus infection alone or from co-infection with bacteria. Flu can also exacerbate chronic medical problems such as heart or lung disease.

The Centers for Disease Control and Prevention (CDC) estimates that so far this season (as of January 12, 2019), between approximately 8.2 million and 9.6 million people have been sick with flu, up to half of those people have sought medical care for their illness, and between 95,000 and 114,000 people have been hospitalized with flu. Between October 1, 2018, and January 12, 2019, nineteen flu-related deaths in children were reported to CDC. Given that significant influenza activity is likely to continue to occur, all of these severity indicators are expected to rise. (Influenza indicators are updated weekly at CDC's Weekly US Influenza Surveillance Report.)

Influenza Vaccination

Yearly flu vaccination for everyone aged 6 months and older is the best way to prevent seasonal flu. While most adults believe that vaccines are important, they need reminders to get vaccinated. Research indicates that adults are more likely to get a flu vaccine if their doctor or healthcare provider recommends it to them. Vaccination should continue as long as influenza activity is elevated, even into January or later. Influenza vaccination can reduce influenza illnesses, doctor visits, and missed work and school due to influenza, as well as prevent influenza-related hospitalizations and deaths.

Influenza Antiviral Medications: Who and When to Treat?

Influenza antiviral medications are an important adjunct to vaccination. Certain people are at greater risk of developing serious influenza-related complications. CDC recommends initiation of antiviral therapy as early as possible for any patient with suspected or confirmed influenza who is hospitalized, has complicated or progressive illness, or is at higher risk for influenza complications. High-risk groups for whom antiviral treatment is recommended include:

  • Children younger than age 2 years (although all children younger than age 5 years are considered at higher risk for complications from influenza, the highest risk is for those younger than age 2 years, with the highest hospitalization and death rates among infants younger than age 6 months)

  • Adults aged 65 years and older

  • People with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), and metabolic (including diabetes mellitus) disorders, or neurologic and neurodevelopment conditions (including disorders of the brain, spinal cord, peripheral nerve, and muscle, such as cerebral palsy, epilepsy, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury)

  • People with immunosuppression, including that caused by medications or by HIV infection

  • Women who are pregnant or postpartum (within 2 weeks after delivery)

  • People younger than age 19 years who are receiving long-term aspirin- or salicylate-containing medications

  • American Indians/Alaska Natives

  • People who are extremely obese (ie, body mass index ≥ 40 kg/m2)

  • Residents of nursing homes and other chronic care facilities

Clinical judgment, based on 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. While antiviral medications work best when given within 2 days of symptom onset, treatment can be given to symptomatic patients with suspected or confirmed flu who are at high risk for flu complications and to hospitalized patients with suspected or confirmed flu, even if they have been sick for more than 2 days. Clinical benefit has been shown in observational studies of hospitalized patients when antiviral treatment was started as late as 4 and 5 days after symptom onset.

Because clinical benefit is greatest when antiviral treatment is started as close to illness onset as possible, decisions about starting antiviral treatment should not wait for laboratory confirmation of influenza.

Antiviral treatment can also be considered for any previously healthy, symptomatic outpatient not at high risk for complications with confirmed or suspected influenza, if treatment can be started within 48 hours of illness onset.

CDC's recommendations for using influenza antiviral medications are based on data from randomized clinical trials, as well as from observational studies of patients receiving treatment in medical practice. Early antiviral treatment in people with influenza can lessen illness severity and shorten the time of illness, and may reduce the risk for some serious flu-related complications such as outpatients with pneumonia requiring antibiotics, and death in hospitalized patients. CDC's influenza antiviral guidance is consistent with the 2018 Clinical Practice Guidelines on Seasonal Influenza, published by the Infectious Diseases Society of America (IDSA), and with the Recommendations for Prevention and Control of Influenza in Children, 2018-2019, published by the American Academy of Pediatrics (AAP). (For more information, see Antiviral References).

Antiviral Options: Which to Choose?

This flu season, four US Food and Drug Administration (FDA)-approved antiviral medications are recommended for the treatment of influenza. Three of these are chemically related antiviral medications known as neuraminidase inhibitors (oral oseltamivir, inhaled zanamivir, and intravenous [IV] peramivir) that have been available previously; the fourth drug is the newly approved oral baloxavir marboxil. Neuraminidase inhibitors are active against both influenza A and B viruses by blocking the viral neuraminidase enzyme. Oral baloxavir is also active against both influenza A and B viruses, but its mechanism of action differs from that of neuraminidase inhibitors. Baloxavir is a cap-dependent endonuclease inhibitor that interferes with viral RNA transcription and blocks virus replication.

Oral oseltamivir is the recommended antiviral for nonhospitalized patients with severe, complicated, or progressive illness, and for hospitalized influenza patients. Oral oseltamivir is also preferred for the treatment of pregnant women. For other outpatients with acute uncomplicated influenza, oral oseltamivir, inhaled zanamivir, IV peramivir, or oral baloxavir may be used for treatment (as age-appropriate).

The recommended treatment course for uncomplicated influenza is two doses per day of oral oseltamivir or inhaled zanamivir for 5 days, or a single infusion of IV peramivir or oral dose of baloxavir. CDC does not recommend use of baloxavir for treatment of pregnant or breastfeeding women because there are no available efficacy or safety data in pregnant women, and there are no available data on the presence of baloxavir in human milk, or the effects of baloxavir on breastfed infants or milk production. Zanamivir is administered using an inhaler device and is not recommended for people with breathing problems like asthma or chronic obstructive pulmonary disease.

Oseltamivir is recommended by CDC, IDSA, and the AAP for treatment of influenza in patients of all ages, including infants (although it's FDA-approved for infants aged 14 days and older). Peramivir is approved for treatment in people aged 2 years and older, zanamivir for treatment for those aged 7 years and older, and baloxavir for treatment for those aged 12 years and older. More information, including antiviral dosage information for different age groups, is available at CDC's Influenza Antiviral Medications: Summary for Clinicians.

Antiviral resistance among circulating influenza viruses to any of the neuraminidase inhibitor antiviral drugs is currently low, but rare, sporadic cases of reduced antiviral susceptibility and resistance can occur. In reaction to the drug's recent FDA approval, CDC has undertaken specific laboratory actions to incorporate baloxavir into routine virologic surveillance. Examples include next-generation sequencing and analysis to assess human seasonal and zoonotic influenza viruses for susceptibility to baloxavir, creation and validation of new assays to determine baloxavir susceptibility, and training of laboratorians to conduct baloxavir susceptibility testing. Reporting of baloxavir susceptibility testing will begin during the 2018-2019 season. CDC publishes weekly surveillance data, including information on reduced antiviral susceptibility and resistance, in the FluView US Influenza Surveillance Report. Information is available on flu antiviral drug reduced susceptibility and resistance.

While vaccination is the most important tool we have to prevent influenza, antiviral medications can be a useful second line of defense to treat influenza illness when indicated. Please see the CDC website for complete guidance on treatment of influenza.

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