COMMENTARY

What to Do About the Flu: CDC 2014-2015 Influenza Antiviral Recommendations

Angela J.P. Campbell, MD, MPH

Disclosures

December 30, 2014

Editorial Collaboration

Medscape &

Editor's Note: January 5, 2015 - This CDC commentary was written before the FDA approval of the influenza antiviral medication peramivir. See FDA Approves Peramivir (Rapivab) for Influenza. CDC is in the process of updating its antiviral guidance to reflect this change.

Drift, Vaccination, and Prevention

Influenza activity is increasing in the United States. CDC is receiving reports of flu-associated illnesses, hospitalizations, and deaths. Influenza A (H3N2) viruses are the most common viruses circulating in the United States. Seasons during which H3N2 have been predominant are often more severe, with more flu hospitalizations and deaths occurring, especially in older people and young children, than during H1N1- or B-predominant seasons. If H3N2 viruses continue to circulate prominently, the 2014-2015 influenza season could be severe.

In addition, most of the H3N2 viruses that have been antigenically or genetically characterized at CDC are different or "drifted" from the H3N2 vaccine virus. During past flu seasons when the predominant circulating influenza viruses have been antigenically drifted, the vaccine's ability to protect against influenza viruses has been reduced. It's possible that reduced vaccine effectiveness may occur this season if these drifted viruses continue to circulate.

Even during seasons when drifted viruses circulate, vaccination remains the first and most important step to prevent flu. Although vaccine effectiveness against the drifted viruses might be reduced, vaccination may reduce severe outcomes such as hospitalization and death. CDC recommends that clinicians continue vaccinating any unvaccinated persons for the remainder of the 2014-2015 season.

Who and When to Treat

However, during seasons when drifted viruses predominate, the appropriate use of influenza antiviral drugs as an adjunct to vaccination becomes even more important. This season, CDC is reminding healthcare professionals about the benefits of antiviral treatment of influenza illness.

The two prescription antiviral medications recommended for treatment or prevention of influenza are oseltamivir (Tamiflu®) and zanamivir (Relenza®). Clinical trials and observational data show that early antiviral treatment can:

Shorten the duration of fever and illness symptoms;

Reduce the risk for complications from influenza, including otitis media in young children and pneumonia requiring antibiotics in adults); and

Reduce the risk for death among hospitalized patients.

Clinical benefit is greatest when antiviral drugs are administered early. When indicated, antiviral treatment should be started as soon as possible after influenza-like illness begins, ideally within 48 hours of symptom onset. However, antiviral treatment might still provide some benefit in patients with severe, complicated, or progressive illness, and in hospitalized patients when started after 48 hours of illness onset.

Antiviral treatment with oral oseltamivir or inhaled zanamivir is recommended as early as possible for any patient with confirmed or suspected influenza who is (1) hospitalized, (2) has severe, complicated, or progressive illness, or (3) is at higher risk for influenza complications, including the following:

Children aged younger than 2 years;

Adults aged 65 years and older;

Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), and metabolic disorders (including diabetes mellitus), 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);

Persons with immunosuppression, including that caused by medications or by HIV infection;

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

Persons aged younger than 19 years who are receiving long-term aspirin therapy;

American Indians/Alaska Natives;

Persons who are morbidly obese (ie, body mass index is equal to or greater than 40); and

Residents of nursing homes and other chronic-care facilities.

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 high-risk outpatients. Decisions about starting antiviral treatment should not wait for test results or laboratory confirmation of influenza.

Choosing an Antiviral

Oseltamivir is approved by the US Food and Drug Administration (FDA) for the treatment of influenza in persons aged 2 weeks and older, and for chemoprophylaxis to prevent influenza in people aged 1 year and older, whereas zanamivir is approved for treatment of persons aged 7 years and older and for prevention of influenza in persons aged 5 years and older.

Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less than 2 weeks old, and for chemoprophylaxis in infants 3 months to 1 year of age, is recommended by the CDC and the American Academy of Pediatrics Committee on Infections Diseases in 2014.

Oral oseltamivir is preferred for the treatment of pregnant women. Pregnant women are recommended to receive the same antiviral dosing as nonpregnant persons.

Clinicians can use their clinical judgment and consider antiviral treatment for previously healthy outpatients with confirmed or suspected influenza who are not in one of the high-risk groups, if treatment can be initiated within 48 hours of illness onset. Clinicians should also consider that a history of influenza vaccination does not rule out the possibility of influenza virus infection in an ill patient with clinical signs and symptoms that are compatible with influenza.

Antiviral resistance to the neuraminidase inhibitor class of antiviral drugs (oseltamivir and zanamivir) among circulating influenza viruses is currently low. So far this season, all influenza viruses tested in the United States have been susceptible to oseltamivir and zanamivir, but sporadic cases of antiviral resistance can occur. Although uncommon, it is possible that some influenza viruses may become resistant to oseltamivir during or after antiviral treatment but remain susceptible to zanamivir. However, severely immunosuppressed persons are at highest risk for the emergence of oseltamivir-resistant influenza virus infection during or following oseltamivir treatment. Treatment with inhaled or intravenous zanamivir may be considered in these cases.

The CDC Influenza Division is available for consultation as needed with respect to the antiviral treatment of severely compromised patients. Resistance of influenza viruses to antiviral drugs can also occur spontaneously, with no known exposure to antiviral medications.

Because high levels of resistance to adamantine antiviral medications continue to be observed among circulating influenza A viruses, adamantines (rimantadine and amantadine) are not recommended for treatment or prevention of influenza.

CDC does not recommend widespread or routine use of antiviral medications for chemoprophylaxis. Indiscriminate use of antivirals for chemoprophylaxis may promote resistance to antiviral medications or reduce antiviral medication availability for treatment of persons at higher risk for influenza complications or those who are severely ill.

Web Resources

A summary of CDC's current influenza antiviral recommendations for clinicians

CDC Health Advisory Regarding the Potential for Circulation of Drifted Influenza A (H3N2) Viruses

Angela J.P. Campbell, MD, MPH, is a Medical Officer for the Epidemiology and Prevention Branch in the Influenza Division in CDC's National Center for Immunization and Respiratory Diseases. Dr Campbell earned her doctor of medicine degree at Vanderbilt University in 1999 and completed training in pediatrics and pediatric infectious diseases at the University of Washington. She also completed the Epidemic Intelligence Service training at CDC and obtained a master of public health in epidemiology degree from the University of Washington School of Public Health. Board certified in pediatrics and pediatric infectious diseases, Dr Campbell was in Seattle for 9 years as a fellow and faculty member in the Department of Pediatrics at the University of Washington before rejoining CDC in March 2013.

Dr Campbell's clinical and research interests over the past decade have focused on factors that influence the acquisition of respiratory virus infection and disease progression among immunocompromised children and adults, with the goal of facilitating new diagnostic, preventive, and treatment strategies for respiratory virus infections. Her current primary research focuses on studies of influenza antiviral treatment and antiviral effectiveness, and she is responsible for developing and revising the CDC clinical guidance related to treatment and prevention of seasonal and novel influenza viruses.

Dr. Campbell is an Affiliate Investigator in the Vaccine and Infectious Disease Division at the Fred Hutchinson Cancer Research Center in Seattle. She is also an Adjunct Assistant Professor of Pediatrics at Emory University School of Medicine, and has an active professional staff appointment at Children's Healthcare of Atlanta.

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