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Influenza Antiviral Medications: Summary for Clinicians

The information on this page should be considered current for the 2017-2018 influenza season for clinical practice regarding the use of influenza antiviral medications.

This page contains excerpts from Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP). PDF Version [1 MB, 28 Pages]

Antiviral medications with activity against influenza viruses are an important adjunct to influenza vaccine in the control of influenza.

  • Influenza antiviral prescription drugs can be used to treat influenza or to prevent influenza.
  • Five licensed prescription influenza antiviral agents are available in the United States.
    • Three influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2017-2018 influenza season: oral oseltamivir (available as a generic version or under the trade name Tamiflu®), inhaled zanamivir (trade name Relenza®), and intravenous peramivir (trade name Rapivab®). These drugs are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses. Generic oseltamivir was approved by the FDA in August 2016 and became available in December of 2016.
    • Amantadine and rimantadine are antiviral drugs in a class of medications known as adamantanes. These medications are active against influenza A viruses, but not influenza B viruses. As in recent past seasons, there continues to be high levels of resistance (>99%) to adamantanes among circulating influenza A(H3N2) and influenza A(H1N1)pdm09 (“2009 H1N1”) viruses. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses.
  • Antiviral resistance to oseltamivir, zanamivir, and peramivir among circulating influenza viruses is currently low, but this can change. Also, antiviral resistance can emerge during or after treatment in some patients (e.g., immunocompromised).

Table 1. Antiviral Medications Recommended for Treatment and Chemoprophylaxis of Influenza

Antiviral Agent Activity Against Use Recommended For Not Recommended for Use in Adverse Events
Oral
Oseltamivir
Influenza A and B Treatment Any age1 N/A Adverse events: nausea, vomiting, headache. Post marketing reports of serious skin reactions and sporadic, transient neuropsychiatric events2
Chemo- prophylaxis 3 months and older1 N/A
Inhaled
Zanamivir
Influenza A and B Treatment 7 yrs and older3 people with underlying respiratory disease (e.g., asthma, COPD)3 Allergic reactions: oropharyngeal or facial edema, skin rash. Adverse events: risk of bronchospasm, especially in the setting of underlying airways disease; sinusitis, dizziness, and ear, nose and throat infections. Post marketing reports of sporadic, transient neuropsychiatric events2
Chemo- prophylaxis 5 yrs and older3 people with underlying respiratory disease (e.g., asthma, COPD)3
Intravenous
Peramivir
Influenza A and B4 Treatment 2 yrs and older4 N/A Adverse events: diarrhea. Post marketing reports of serious skin reactions and sporadic, transient neuropsychiatric events2
Chemo- prophylaxis N/A N/A

Abbreviations: N/A = not applicable, COPD = chronic obstructive pulmonary disease.

1 Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in persons 14 days and older, and for chemoprophylaxis in persons 1 year and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less 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.

2 Self-injury or delirium; mainly reported among Japanese adolescents and adults.

3 Inhaled zanamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in persons aged 7 years and older, and for chemoprophylaxis of influenza in persons aged 5 years and older. Inhaled zanamivir is contraindicated in patients with history of allergy to milk protein.

4 Intravenous peramivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in persons aged 2 years and older. Peramivir efficacy is based on clinical trials in which the predominant influenza virus type was influenza A; a limited number of subjects infected with influenza B virus were enrolled.

Summary of 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 adult influenza patients has been reported to reduce death.
    • In hospitalized children, early antiviral treatment has been reported 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.
  • Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.

Persons at higher risk for influenza complications recommended for antiviral treatment include:

  • children aged younger than 2 years;1
  • 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, 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 extremely obese (i.e., body mass index is equal to or greater than 40); and
  • residents of nursing homes and other chronic care facilities.

(Adapted from Fiore, 2011, Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza – Recommendations of the Advisory Committee on Immunization Practices (ACIP)PDF Version [1 MB, 29 Pages])

1 Although all children aged younger than 5 years are considered at higher risk for complications from influenza, the highest risk is for those aged younger than 2 years, with the highest hospitalization and death rates among infants aged younger than 6 months. Because many children with mild febrile respiratory illness might have other viral infections (e.g., respiratory syncytial virus, rhinovirus, parainfluenza virus, or human metapneumovirus), knowledge of other respiratory viruses as well as influenza virus strains circulating in the community is important for treatment decisions.

  • 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.
  • When indicated, antiviral treatment should be started as soon as possible after illness onset, ideally within 48 hours of symptom onset. However, antiviral treatment might have some benefits in patients with severe, complicated or progressive illness, and in hospitalized patients when started after 48 hours of illness onset.
    • Observational studies in hospitalized patients with influenza have reported that clinical benefit is greatest when oseltamivir is started within 48 hours of illness onset (Hsu, 2012; Louie, 2013; Muthuri, 2013; Muthuri, 2014). However, some studies suggest that antiviral treatment might still be beneficial in hospitalized patients when started up to 4 or 5 days after illness onset (Louie, 2012; Yu, 2011). Antiviral treatment of pregnant women (of any trimester) with influenza A(H1N1)pdm09 virus infection has been shown to be most beneficial in preventing respiratory failure and death when started within less than 3 days of illness onset, but still provided benefit when started 3–4 days after onset compared to 5 or more days (Siston, 2010).
  • Decisions about starting antiviral treatment should not wait for laboratory confirmation of influenza (see resources regarding Clinical Description and Lab Diagnosis of Influenza for more information on influenza diagnostic testing).
    • Clinical benefit is greatest when antiviral treatment is started as close to illness onset as possible.
  • While influenza vaccination is the best way to prevent influenza illness, a history of influenza vaccination does not rule out the possibility of influenza virus infection in an ill patient with clinical signs and symptoms compatible with influenza.
  • Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk with confirmed or suspected influenza on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset. Multiple randomized controlled clinical trials (RCTs) and meta-analyses of RCTs have demonstrated efficacy of early initiation of treatment (started within 48 hours of illness onset) with neuraminidase inhibitors in reducing duration of fever and illness symptoms compared with placebo in otherwise healthy children and adults with uncomplicated influenza (Hayden, 1997; Monto, 1999; Monto, 1999; Nicholson, 2000; Hedrick, 2000; Treanor, 2000; Whitley, 2001; Heinonen, 2010; Fry, 2014; Whitley, 2015; Kohno, 2010; Hsu, 2012; Jefferson, 2014; Whitley, 2015;, Dobson, 2015; Malosh, 2017).
    • One randomized clinical trial in children with uncomplicated influenza demonstrated a modest reduction in duration of symptoms and influenza virus shedding in patients initiating treatment after 48 hours; post hoc analysis suggested that treatment initiated 72 hours after illness onset reduced symptoms by one day compared with placebo (Fry, 2014).
  • For outpatients with acute uncomplicated influenza, oral oseltamivir, inhaled zanamivir, or intravenous peramivir may be used for treatment.
    • The recommended treatment course for uncomplicated influenza is two doses per day of oral oseltamivir or inhaled zanamivir for 5 days, or one dose of intravenous peramivir for 1 day.
  • For patients with severe or complicated illness with suspected or confirmed influenza who are not hospitalized, antiviral treatment with oral or enterically-administered oseltamivir is recommended as soon as possible. Inhaled zanamivir is not recommended because of the lack of data for use in patients with severe influenza disease.
  • Oral oseltamivir is preferred for treatment of pregnant women (Rasmussen, 2009; 2011). Pregnant women are recommended to receive the same antiviral dosing as non-pregnant persons. Multiple recent studies have reported safe use of neuraminidase inhibitors during pregnancy (Dunstan, 2014; Xie, 2013; Saito, 2013; Wollenhaupt, 2014; Beau, 2014; Svensson, 2011; Greer, 2010; Graner, 2017). See Recommendations for Obstetric Health Care Providers Related to Use of Antiviral Medications in the Treatment and Prevention of Influenza for additional information.

Treatment Considerations for Patients Hospitalized with Suspected or Confirmed Influenza

Treatment of patients with severe influenza (e.g., those requiring hospitalization) presents multiple challenges. The effect of specific antiviral strategies in serious or life-threatening influenza is not established from clinical trials conducted to support licensure of oral oseltamivir, inhaled zanamivir, or intravenous peramivir, as those studies were conducted primarily among previously healthy outpatients with uncomplicated illness. No randomized, placebo-controlled clinical trials have been conducted of neuraminidase inhibitors for treatment of influenza in hospitalized patients. However, a number of observational studies in hospitalized influenza patients have shown clinical benefit of neuraminidase inhibitor antiviral treatment compared with no treatment, particularly when started within two days of influenza illness, including reducing the duration of hospitalization or risk of death (Hiba, 2011; Coffin, 2011; Hsu, 2012; Louie, 2013; Muthuri, 2013; Muthuri, 2014).  In addition, some observational studies have reported that oral oseltamivir treatment started 4 and 5 days after illness onset in  patients hospitalized with suspected or confirmed influenza was  associated with lower risk for severe outcomes (EH Lee, 2010; N Lee, 2008; N Lee, 2010; Louie, 2012; McGeer, 2007; Siston, 2010), although one report found this benefit only in hospitalized adult patients in the ICU [Muthuri 2014]. A small number of observational studies and one meta-analysis of observational studies of hospitalized influenza patients reported that neuraminidase inhibitor treatment did not have survival benefit (Choi, 2017; Wolkewitz, 2016; Heneghan, 2016).

The following recommendations do not necessarily represent FDA-approved uses of antiviral products, but are based on published observational studies and expert opinion and are subject to change as the developmental status of investigational products and the epidemiologic and virologic features of influenza change over time.

  • For hospitalized patients with suspected or confirmed influenza, initiation of antiviral treatment with oral or enterically-administered oseltamivir is recommended as soon as possible. Antiviral treatment might be effective in reducing morbidity and mortality in hospitalized influenza patients, especially adults, even if treatment is started more than 48 hours after onset of illness.
  • Inhaled zanamivir is not recommended because of the lack of data in hospitalized influenza patients. There is also insufficient data for treatment of hospitalized influenza patients with intravenous peramivir.
  • For patients with lower respiratory tract disease, lower respiratory tract specimens, such as bronchoalveolar lavage fluid or endotracheal aspirates, are preferred; an oropharyngeal (throat) swab may be collected if lower respiratory specimens are not available. Testing of lower respiratory tract specimens may detect influenza viruses when testing of upper respiratory tract specimens is negative. Multiple respiratory tract specimens collected on different days should be tested if influenza virus infection is suspected but a definitive diagnosis has not been made.
  • The optimal duration and dosing of antiviral treatment are uncertain for severe or complicated influenza. Treatment regimens might need to be altered to fit the clinical circumstances. For example, clinical judgment should be the guide regarding the need to extend daily treatment regimens longer than 5 days for patients whose illness is prolonged. Critically ill patients with respiratory failure can have prolonged influenza viral replication in the lower respiratory tract and might benefit from longer duration of treatment.
    • Clinical judgment and virologic testing of lower respiratory tract specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR) should guide decisions to consider treatment regimens longer than 5 days for hospitalized influenza patients with severe and prolonged illness.
    • Longer treatment regimens might be necessary in immunosuppressed persons who may have prolonged influenza viral replication. Such patients are at risk of developing antiviral-resistant virus during or after antiviral treatment.
    • A higher dose of oral or enterically-administered oseltamivir has been recommended by some experts (e.g., 150 mg twice daily in adults with normal renal function) for treatment of influenza in immunocompromised patients and in severely ill hospitalized patients. However, oral or enterically administered oseltamivir has been reported to be adequately absorbed in critically ill adults, with standard doses producing therapeutic blood levels (Ariano, 2010), and available data suggest that higher dosing may not provide additional clinical benefit (Abdel-Ghafar, 2008; Ariano, 2010; Kumar, 2010; Lee, 2013; South East Asia Infectious Disease Clinical Research Network, 2013). Studies indicate that the exposure to oseltamivir carboxylate (the active metabolite of oseltamivir) is similar between obese and non-obese subjects for both 75 mg and 150 mg doses given twice daily (Ariano, 2010; Jittamala, 2014; Pai, 2011; Thorne-Humphrey, 2011).
  • Limited data suggest that oseltamivir administered orally or by oro/naso gastric tube is well absorbed in critically ill influenza patients, including those receiving continuous renal replacement therapy, and/or on extracorporeal membrane oxygenation (Ariano, 2010; Eyler, 2012a; Eyler, 2012b; Giraud, 2011; Kromdijk, 2013; Lemaitre, 2012; Mulla, 2013; Taylor, 2008).
  • 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 should be considered.
    • In a randomized trial of treatment of influenza in hospitalized patients aged >6 years, a significant clinical benefit was not demonstrated for intravenous peramivir at a dosage of 600 mg once daily (10 mg/kg once daily in children) for five days plus standard of care compared with placebo plus standard of care; however, peramivir was generally safe and well tolerated (de Jong, 2014).
  • It is possible that some influenza viruses may become resistant to oseltamivir and peramivir during antiviral treatment with one of these agents and remain susceptible to zanamivir; this has been reported most often for influenza A(H1N1) viruses (Graitcer, 2011; Lackenby, 2011; Memoli, 2010; Nguyen, 2010; Nguyen, 2012). Resistance of influenza viruses to antiviral drugs can also occur spontaneously, with no known exposure to antiviral medications (Hurt, 2011; Takashita, 2013; Takashita, 2014).
  • If a hospitalized patient treated with oseltamivir or peramivir manifests progressive lower respiratory symptoms, resistant virus should be considered. However, clinicians should note that failure to improve or clinical deterioration during oseltamivir or peramivir treatment is more likely to be related to the natural history of acute lung injury and inflammatory damage or onset of other complications (e.g., renal failure, septic shock, ventilator-associated pneumonia) than to emergence of oseltamivir or peramivir resistance. Severely immunosuppressed persons (e.g., hematopoietic stem cell transplant recipients) are at highest risk for emergence of oseltamivir- and peramivir-resistant influenza virus infection during or following oseltamivir and/or peramivir treatment (Hurt, 2012; Memoli, 2010). Molecular analyses can detect genetic changes in influenza viruses associated with oseltamivir and peramivir resistance. The CDC Influenza Division is available for consultation regarding antiviral resistance testing as needed.
  • Intravenous zanamivir is an investigational parenterally administered neuraminidase inhibitor product that has been available in the past through enrollment in a clinical trial or under an emergency investigational new drug (EIND) request to the manufacturer. However, as of the 2017-18 season, intravenous zanamivir is no longer available in the United States.
  • Careful attention to ventilator and fluid management and to the prevention and treatment of secondary bacterial pneumonia (e.g., S. pneumoniae, S. pyogenes, and S. aureus, including MRSA) also is critical for severely ill patients (Bautista, 2010; Finelli, 2008; Hageman, 2006; Harper, 2009; Mandell, 2007; Mauad, 2010; Shieh, 2010).

Diagnostic Testing for Influenza

Information on Local Influenza Activity

  • Clinicians should contact their local or state health department for information about current influenza activity. For more information about influenza activity in the United States during the influenza season, visit the Weekly U.S. Influenza Surveillance Report (FluView).

Table 2. Recommended Dosage and Duration of Influenza Antiviral Medications for Treatment or Chemoprophylaxis

Antiviral Agent Use Children Adults
Oral
Oseltamivir
Treatment
(5 days)1
If younger than 1 yr old2:
3 mg/kg/dose twice daily3,4If 1 yr or older, dose varies by child’s weight: 15 kg or less, the dose is 30 mg twice a day
>15 to 23 kg, the dose is 45 mg twice a day
>23 to 40 kg, the dose is 60 mg twice a day
>40 kg, the dose is 75 mg twice a day
75 mg twice daily
Chemo-prophylaxis
(7 days)5
If child is younger than 3 months old, use of oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group. If child is 3 months or older and younger than 1 yr old2 3 mg/kg/dose once daily3If 1 yr or older, dose varies by child’s weight: 15 kg or less, the dose is 30 mg once a day
>15 to 23 kg, the dose is 45 mg once a day
>23 to 40 kg, the dose is 60 mg once a day
>40 kg, the dose is 75 mg once a day
75 mg once daily
Inhaled
Zanamivir6
Treatment
(5 days)
10 mg (two 5-mg inhalations) twice daily
(FDA approved and recommended for use in children 7 yrs or older)
10 mg (two 5-mg inhalations) twice daily
Chemo-prophylaxis
(7 days)5
10 mg (two 5-mg inhalations) once daily
(FDA approved for and recommended for use in children 5 yrs or older)
10 mg (two 5-mg inhalations) once daily
Intravenous
Peramivir7
Treatment
(1 day)1
(2 to 12 yrs of age) One 12 mg/kg dose, up to 600 mg maximum, via intravenous infusion for a minimum of 15 minutes
(FDA approved and recommended for use in children 2 yrs or older)
(13 yrs and older) One 600 mg dose, via intravenous infusion for a minimum of 15 minutes
Chemo-prophylaxis N/A N/A

Abbreviations: N/A = not applicable

Longer treatment duration may be needed for severely ill patients.

Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in persons 14 days and older, and for chemoprophylaxis with once-daily dosing in persons 1 year and older. Although not part of the FDA-approved indications, use of oral oseltamivir for treatment of influenza in infants less 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 (Committee on Infectious Diseases, 2017).

This is the FDA-approved oral oseltamivir treatment dose for infants 14 days and older and less than 1 year old, and provides oseltamivir exposure in children similar to that achieved by the approved dose of 75 mg orally twice daily for adults, as shown in two studies of oseltamivir pharmacokinetics in children (Kimberlin, 2013 [CASG 114], EU study WP22849, FDA Clinical Pharmacology Review). The American Academy of Pediatrics has recommended an oseltamivir treatment dose of 3.5 mg/kg orally twice daily for infants aged 9-11 months, on the basis of data which indicated that a higher dose of 3.5 mg/kg was needed to achieve the protocol-defined targeted exposure for this cohort as defined in the CASG 114 study (Kimberlin, 2013). It is unknown whether this higher dose will improve efficacy or prevent the development of antiviral resistance. However, there is no evidence that the 3.5 mg/kg dose is harmful or causes more adverse events to infants in this age group.

4 Current weight-based dosing recommendations are not appropriate for premature infants. Premature infants might have slower clearance of oral oseltamivir because of immature renal function, and doses recommended for full-term infants might lead to very high drug concentrations in this age group. CDC recommends dosing as also recommended by the American Academy of Pediatrics (Committee on Infectious Diseases, 2017): limited data from the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group provide the basis for dosing preterm infants using their postmenstrual age (gestational age + chronological age): 1.0 mg/kg/dose, orally, twice daily, for those <38 weeks postmenstrual age; 1.5 mg/kg/dose, orally, twice daily, for those 38 through 40 weeks postmenstrual age; 3.0 mg/kg/dose, orally, twice daily, for those >40 weeks postmenstrual age.

See Special Considerations for Institutional Settings section below for details regarding duration of chemoprophylaxis for outbreaks in institutional settings.

6 Inhaled zanamivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in persons aged 7 years and older, and for chemoprophylaxis with once-daily dosing in persons aged 5 years and older.

7 Intravenous peramivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with a single dose in persons aged 2 years and older. Daily dosing for a minimum of 5 days was used in clinical trials of hospitalized patients with influenza (de Jong, 2014, Ison, 2014).

Duration of Treatment or Chemoprophylaxis

Treatment: Recommended duration for antiviral treatment is 5 days for oral oseltamivir or inhaled zanamivir. For the treatment of uncomplicated influenza with intravenous peramivir, a single dose is recommended. Longer daily dosing (oral oseltamivir or intravenous peramivir) can be considered for patients who remain severely ill after 5 days of treatment.

Chemo prophylaxis: Recommended duration is 7 days (after last known exposure). For control of outbreaks in institutional settings (e.g. long-term care facilities for elderly persons and children) and hospitals, CDC recommends antiviral chemoprophylaxis for a minimum of 2 weeks, and continuing up to 1 week after the last known case was identified. Antiviral chemoprophylaxis is recommended for all residents, including those who have received influenza vaccination.

Chemoprophylaxis

  • Annual influenza vaccination is the best way to prevent influenza because vaccination can be given well before influenza virus exposures occur, and can provide safe and effective immunity throughout the influenza season.
  • Antiviral medications are approximately 70% to 90% effective in preventing influenza and are useful adjuncts to influenza vaccination.
  • CDC does not recommend widespread or routine use of antiviral medications for chemoprophylaxis except as one of multiple interventions to control institutional influenza outbreaks. Routine use of post-exposure chemoprophylaxis is not recommended; one reason for this is to avoid sub-therapeutic treatment dosing if infection is already established, although the possibility of whether antiviral resistant viruses could emerge is unknown.
  • In general, CDC does not recommend seasonal or pre-exposure antiviral chemoprophylaxis, but antiviral medications can be considered for chemoprophylaxis to prevent influenza in certain situations, such as the following examples:
    • Prevention of influenza in persons at high risk of influenza complications during the first two weeks following vaccination after exposure to a person with influenza.
    • Prevention for people at high risk for complications from influenza who cannot receive influenza vaccine due to a contraindication after exposure to a person with influenza.
    • Prevention for people with severe immune deficiencies or others who might not respond to influenza vaccination, such as persons receiving immunosuppressive medications, after exposure to a person with influenza.
  • An emphasis on close monitoring and early initiation of antiviral treatment if fever and/or respiratory symptoms develop is an alternative to chemoprophylaxis after a suspected exposure for some persons.
  • To be effective as chemoprophylaxis, an antiviral medication must be taken each day for the duration of potential exposure to a person with influenza and continued for 7 days after the last known exposure. For persons taking antiviral chemoprophylaxis after inactivated influenza vaccination, the recommended duration is until immunity after vaccination develops (antibody development after vaccination takes about two weeks in adults and can take longer in children depending on age and vaccination history).
  • Antiviral chemoprophylaxis generally is not recommended if more than 48 hours have elapsed since the first exposure to a person with influenza.
  • Patients receiving antiviral chemoprophylaxis should be encouraged to seek medical evaluation as soon as they develop a febrile respiratory illness that might indicate influenza.

Special Considerations for Institutional Settings

Use of antiviral chemoprophylaxis to control outbreaks among high risk persons in institutional settings, such as long term care facilities, is recommended.

  • An influenza outbreak is likely when at least two residents are ill within 72 hours, and at least one has laboratory confirmed influenza. When influenza viruses are circulating in the community, even one positive laboratory result in conjunction with other compatible illnesses on the unit indicates that an outbreak of influenza is likely occurring.
  • When influenza is identified as a cause of a respiratory disease outbreak among nursing home residents, use of antiviral medications for chemoprophylaxis is recommended for all non-ill residents (regardless of whether they have received influenza vaccination). Antiviral chemoprophylaxis is meant for residents who are not exhibiting influenza-like illness but who may be exposed or who may have been exposed to an ill person with influenza, to prevent transmission.
  • For unvaccinated health care personnel, antiviral chemoprophylaxis can be offered. For newly-vaccinated staff, antiviral chemoprophylaxis can be offered for up to two weeks (the time needed for antibody development) following influenza vaccination. Chemoprophylaxis can also be offered for all employees, regardless of their influenza vaccination status, if the outbreak is caused by a strain of influenza virus that is not well-matched by the vaccine. As noted above, an emphasis on close monitoring for signs and symptoms of influenza, and initiation of early antiviral treatment is an alternative to chemoprophylaxis for health care personnel.
  • For institutional outbreak management, antiviral chemoprophylaxis should be administered for a minimum of two weeks, and continue for at least seven days after the last known case was identified.

For more information on the control of institutional outbreaks, please see CDC’s Interim Guidance for Influenza Outbreak Management in Long-Term Care Facilities and the IDSA guidelines web sit [259 KB, 30 Pages].

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Dosing in Adult Patients with Renal Impairment

Dose adjustment of oseltamivir is recommended for patients with creatinine clearance between 10 and 60 mL/min and patients with end-stage renal disease (ESRD) undergoing hemodialysis or continuous peritoneal dialysis receiving oseltamivir for the treatment or chemoprophylaxis of influenza. Oseltamivir is not recommended for patients with ESRD not undergoing dialysis. The recommended doses are detailed in Table 3; duration of treatment and chemoprophylaxis is the same as recommended for patients with normal renal function. No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment. The dose of intravenous peramivir should be reduced for patients with baseline creatinine clearance below 50 mL/min (see Table 3).

Table 3. Recommended Oseltamivir and Peramivir Dose Adjustments for Treatment or Chemoprophylaxis of Influenza in Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis*

Creatinine Clearance Recommended Treatment Regimen Recommended Chemoprophylaxis Regimen
Oral oseltamivir1 Creatinine clearance 61 to 90 mL/min 75 mg twice a day 75 mg once daily
Creatinine clearance 31 to 60 mL/min 30 mg twice a day 30 mg once daily
Creatinine clearance 11 to 30 mL/min 30 mg once daily 30 mg every other day
ESRD Patients on Hemodialysis
Creatinine clearance ≤10 mL/min
30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days2 30 mg after alternate hemodialysis cycles3
ESRD Patients on Continuous Ambulatory Peritoneal Dialysis4 Creatinine clearance ≤10 mL/min A single 30 mg dose administered immediately after a dialysis exchange 30 mg once weekly immediately after dialysis exchange
Intravenous Peramivir (single dose)5 Creatinine clearance ≥50 mL/min 600 mg N/A
Creatinine clearance 30 to 49 mL/min 200 mg N/A
Creatinine clearance 10 to 29 mL/min 100 mg N/A
ESRD Patients on Hemodialysis Dose administered after dialysis at a dose adjusted based on creatinine clearance

* From package inserts for oseltamivir and peramivir; see FDA Influenza (Flu) Antiviral Drugs and Related Information.

Abbreviations: N/A = not applicable

Renal dosing of oseltamivir is not available in the package insert for pediatric patients. However, these tables may be useful for children who qualify for adult doses based on weight >40 kg.

Assuming 3 hemodialysis sessions are performed in the 5- day period. Treatment can be initiated immediately if influenza symptoms develop during the 48 hours between hemodialysis sessions; however, the post-hemodialysis dose should still be administered independently of time of administration of the initial dose.

An initial dose can be administered prior to the start of dialysis.

Data derived from studies in continuous ambulatory peritoneal dialysis (CAPD) patients.

Renal dosing from peramivir package insert is available for pediatric patients: Creatinine clearance ≥50 mL/min: 12 mg/kg (up to maximum dose of 600 mg); Creatinine clearance 30 to 49 mL/min: 4 mg/kg; Creatinine clearance 10 to 29 mL/min: 2 mg/kg.

Adverse Events

    • When considering use of influenza antiviral medications, clinicians must consider the patient’s age, weight and renal function; presence of other medical conditions; indications for use (i.e., chemoprophylaxis or therapy); and the potential for interaction with other medications.
    • RCTs and meta-analyses of RCTs have indicated that gastrointestinal symptoms such as nausea and vomiting are increased with oral oseltamivir compared with placebo; these adverse events may be less likely when taken with food (Aoki, 2003).
    • For more information on safety, effectiveness and dosing for oral oseltamivir, inhaled zanamivir, and intravenous peramivir, visit Antiviral Drugs or consult the package inserts.

For more information, visit the Seasonal Influenza (Flu) site, email CDC-INFO, or call CDC at 800-CDC-INFO (English and Spanish) or 888-232-6348 (TTY).

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References

For a more complete list of influenza antiviral references, please see Antiviral Guide References (Antiviral Guide References).

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