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.

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.

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.


CDC Antiviral Recommendations

CDC recommends antiviral medications for treatment of influenza as an important adjunct to annual influenza vaccination. Treatment with neuraminidase inhibitors has been shown to have clinical and public health benefit in reducing illness and severe outcomes of influenza, as evidenced from randomized controlled trials, meta-analyses of randomized controlled trials, and observational studies of oral oseltamivir, inhaled zanamivir, or parenteral peramivir treatment during past influenza seasons and during the 2009 H1N1 pandemic.

CDC Influenza Antiviral Treatment Recommendations

  • Clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of complications from influenza (e.g., otitis media in young children, pneumonia, and respiratory failure).
  • Early treatment of hospitalized patients can reduce death.
  • In hospitalized children, early antiviral treatment has been shown to shorten the duration of hospitalization.
  • Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of influenza illness onset.
  • Antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influenza who: is hospitalized; has severe, complicated, or progressive illness; or is at higher risk for influenza complications.

All Hospitalized, Severely ill, and High Risk Patients with Suspected Influenza Should Be Treated with Antivirals

Any patient with suspected or confirmed influenza in the following categories should be treated with a neuraminidase inhibitor:

1) Hospitalized – treatment is recommended for all hospitalized patients
2) Severe, complicated, or progressive illness – this may include outpatients with severe or prolonged     progressive symptoms or who develop complications such as pneumonia
3) High risk for influenza complications (hospitalized or outpatient) – patients in this group include:

    • children younger than 2 years (although all children younger than 5 years are considered at higher risk for complications from influenza, the highest risk is for those younger than 2 years);
    • adults aged 65 years and older;
    • persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (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 [seizure disorders], stroke, intellectual disability [mental retardation], 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 (i.e., body-mass index is equal to or greater than 40); and
    • residents of nursing homes and other chronic-care facilities.


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