COMMENTARY

Treating Flu: CDC 2015-2016 Influenza Antiviral Recommendations

Angela Campbell, MD, MPH

Disclosures

January 25, 2016

Editorial Collaboration

Medscape &

Vaccination and Prevention

Influenza activity is increasing in the United States. Influenza activity most often peaks in February and can last into May. Vaccination remains the first and most important step to prevent influenza. Influenza vaccines for the 2015-2016 season have been updated to better match circulating influenza viruses, and CDC recommends that clinicians continue vaccinating any unvaccinated persons during the remainder of the 2015-2016 season.

Who and When to Treat

An important adjunct to vaccination is the use of antiviral medications for the treatment of influenza. Rapid treatment is especially important for people with confirmed influenza or with influenza symptoms who are very sick or who are at high risk for influenza complications.

The three prescription antiviral medications recommended for treatment of influenza are Tamiflu® (oral oseltamivir), Relenza® (inhaled zanamivir), and Rapivab® (intravenous peramivir). These drugs are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses.

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 illness begins, ideally within 48 hours of symptom onset. However, antiviral treatment might still provide some benefit in hospitalized patients when started after 48 hours of illness onset.

Antiviral treatment with a neuraminidase inhibitor 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 ≥ 40 kg/m2); 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

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

Inhaled zanamivir is approved for treatment of persons aged 7 years and older and for prevention of influenza in persons aged 5 years and older. Intravenous peramivir was approved in December 2014, for the treatment of influenza in persons aged 18 years and older. Oral oseltamivir is preferred for the treatment of pregnant women. Pregnant women are recommended to receive the same antiviral dosing as nonpregnant persons.

Antiviral treatment can be considered on the basis of clinical judgment for previously healthy symptomatic outpatients with confirmed or suspected influenza who are not at high risk for influenza complications, if treatment can be initiated within 48 hours of illness onset. Clinicians also should keep in mind 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.

For all patients hospitalized with suspected or confirmed influenza, treatment with oral or enterically administered oseltamivir is recommended. Limited data suggest that oseltamivir administered orally or by orogastric/nasogastric tube is well absorbed in critically ill influenza patients. However, for patients who cannot tolerate or absorb oral or enterically administered oseltamivir because of suspected or known gastric stasis, malabsorption, or gastrointestinal bleeding, the use of intravenous peramivir or investigational intravenous zanamivir should be considered.

Antiviral resistance to any of the neuraminidase inhibitor antiviral drugs (oseltamivir, zanamivir, and peramivir) among circulating influenza viruses is currently low. So far this season, the vast majority of influenza viruses tested in the United States have been susceptible to oseltamivir, zanamivir, and peramivir, but rare, sporadic cases of antiviral resistance can occur. CDC publishes weekly surveillance data on antiviral resistance in the FluView US Influenza Surveillance Report.

Although uncommon, it is possible that some influenza viruses may become resistant to oseltamivir and peramivir during or after treatment with oseltamivir or peramivir but remain susceptible to zanamivir. Resistance of influenza viruses to antiviral drugs also can occur spontaneously, with no known exposure to antiviral medications. In view of the limited alternatives, CDC recommends that investigational use of intravenous zanamivir should be considered for treatment of severely ill patients with suspected or confirmed oseltamivir/peramivir-resistant virus infection. Molecular assays can detect genetic changes in influenza viruses that have been associated with oseltamivir and peramivir resistance. The CDC Influenza Division is available for consultation as needed.

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

Web Resources

Influenza Antiviral Medications: Summary for Clinicians

FluView US Influenza Surveillance Report

FluView Interactive

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