Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Influenza Antiviral Medications: Summary for Clinicians

The information on this page should be considered current for the 2018-2019 influenza season for clinical practice regarding the use of influenza antiviral medications.

In addition to current season updates, 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, and some can be used to prevent influenza.
  • Six licensed prescription influenza antiviral drugs are approved in the United States.
    • Four influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2018-2019 influenza season.
      • Three drugs are chemically related antiviral medications known as neuraminidase inhibitors that block the viral neuraminidase enzyme and have activity against both influenza A and B viruses:  oral oseltamivir phosphate (available as a generic version or under the trade name Tamiflu®), inhaled zanamivir (trade name Relenza®), and intravenous peramivir (trade name Rapivab®).
      • The fourth drug is oral baloxavir marboxil (trade name Xofluza®), which is active against both influenza A and B viruses, but has a different mechanism of action than neuraminidase inhibitors.  Baloxavir is a cap-dependent endonuclease inhibitor that interferes with viral RNA transcription and blocks virus replication.
      • More information regarding the four recommended antiviral medications is available: Table 1.
  • Amantadine and rimantadine are antiviral drugs in a class of medications known as adamantanes, which target the M2 ion channel protein of influenza A viruses. Therefore, 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 and reduced susceptibility to the neuraminidase inhibitors and to baloxavir among circulating influenza viruses is currently low, but this can change. Antiviral resistance and reduced susceptibility can occur sporadically, or emerge during or after antiviral treatment in some patients (e.g., immunocompromised). Following treatment with baloxavir, emergence of viruses with molecular markers associated with reduced susceptibility to baloxavir has been observed in clinical trials (Hayden, 2018; Omoto, 2018).
  • For weekly surveillance data on susceptibility of circulating viruses to antivirals this season, see the FluView U.S. Influenza Surveillance Report.

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 Adverse events: risk of bronchospasm, especially in the setting of underlying airways disease; sinusitis, and dizziness.. Post marketing reports of serious skin reactions and 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- prophylaxis5 Not recommended N/A
Oral
Baloxavir		 Influenza A and B6 Treatment 12 yrs and older6 N/A Adverse events: none more common than placebo in clinical trials
Chemo- prophylaxis5 Not recommended N/A

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

1 Oral oseltamivir phosphate is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in people 14 days and older, and for chemoprophylaxis in people 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, 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 pediatric patients.

3 Inhaled zanamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in people 7 years and older, and for chemoprophylaxis of influenza in people 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 people 2 years and older. Peramivir efficacy is based on clinical trials versus placebo in which the predominant influenza virus type was influenza A; in one trial, a very limited number of subjects infected with influenza B virus were enrolled.

5 There are no data for use of peramivir or baloxavir for chemoprophylaxis of influenza.

6 Oral baloxavir marboxil is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset in people 12 years and older. The safety and efficacy of baloxavir for the treatment of influenza have been established in pediatric patients 12 years and older weighing at least 40 kg. Safety and efficacy in patients less than 12 years of age or weighing less than 40 kg have not been established. Baloxavir efficacy is based on clinical trials in outpatients 12 to 64 years of age; people with underlying medical conditions and adults >65 years and older were not included in the initial published clinical trials (Hayden, 2018). There are no available data for baloxavir treatment of hospitalized patients with influenza.

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 some complications from influenza (e.g., otitis media in young children, pneumonia, and respiratory failure).
    • Early treatment of hospitalized adult influenza patients with oseltamivir has been reported to reduce death in some observational studies.
    • In hospitalized children, early antiviral treatment with oseltamivir has been reported to shorten the duration of hospitalization in observational studies.
    • Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of influenza illness onset in clinical trials and observational studies.
  • 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.
  • *Note: Oral oseltamivir is the recommended antiviral for patients with severe, complicated, or progressive illness who are not hospitalized, and for hospitalized influenza patients.
  • Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications, who is diagnosed with confirmed or suspected influenza, on the basis of clinical judgment, if treatment can be initiated within 48 hours of illness onset.

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

  • children younger than 2 years;1
  • adults 65 years and older;
  • people 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);
  • 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 19 years old who are receiving long-term aspirin- or salicylate-containing medications
  • American Indians/Alaska Natives;
  • people 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.

  • 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). One observational study reported that initiating neuraminidase inhibitor treatment within 6 hours after hospital admission was associated with shorter duration of hospitalization versus starting antiviral treatment later (Katzen, 2018).
  • 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 oseltamivir 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, intravenous peramivir, or oral baloxavir 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 or oral baloxavir for 1 day.
    • CDC does not recommend use of baloxavir for treatment of pregnant women or breastfeeding mothers. 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, the effects on the breastfed infant, or the effects on milk production.
    • There are no available data on the use of baloxavir for treatment of influenza more than 2 days after illness onset.
  • 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 people. 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); Ehrenstien, 2018). See Recommendations for Obstetric Health Care Providers Related to Use of Antiviral Medications in the Treatment and Prevention of Influenza for additional information. Baloxavir is not recommended for the treatment of pregnant women, as there are no available efficacy or safety data.
  • For patients with severe or complicated illness with suspected or confirmed influenza (e.g., pneumonia, or exacerbation of underlying chronic medical condition) who are not hospitalized, antiviral treatment with oral or enterically-administered oseltamivir is recommended as soon as possible. There are insufficient data for inhaled zanamivir and intravenous peramivir in patients with severe influenza disease. There are no available data on use of baloxavir in patients with severe influenza disease.

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,  intravenous peramivir, or oral baloxavir, 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 and oral baloxavir are not recommended because of the lack of data in hospitalized influenza patients. There are 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 people who may have prolonged influenza viral replication. Such patients are at risk of emergence of influenza viruses with reduced susceptibility or antiviral resistance 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 (Lee, 2017; deJong, 2014; Ison, 2014; Ison, 2013).
      • In a randomized trial of treatment of influenza in hospitalized patients >6 years old, 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 less susceptible or resistant to oseltamivir and peramivir during antiviral treatment with one of these drugs and remain susceptible to zanamivir; this has been reported most often for influenza A(H1N1)pdm09 viruses (Graitcer, 2011; Lackenby, 2011; Memoli, 2010; Nguyen, 2010; Nguyen, 2012) Influenza A(H1N1)pdm09 viruses have also emerged that are resistant to all neuraminidase inhibitors, including zanamivir, in highly immunosuppressed patients on prolonged neuraminidase inhibitor treatment (Tamura, 2015; L’Huillier, 2015). Resistance and reduced susceptibility 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 people (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 resistance and reduced susceptibility to oseltamivir and peramivir. The CDC Influenza Division is available for consultation regarding antiviral susceptibility testing as needed. Information about neuraminidase inhibitor susceptibility testing and interpretation of results of neuraminidase inhibition assays is available on the WHO website.
  • 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, since 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 daily3,4 If 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 daily3 If 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-prophylaxis8 Not recommended N/A
Oral Baloxavir9 Treatment
(1 day)1 		FDA approved and recommended for use in children 12 yrs or older weighing at least 40 kg. See adult dosage. (12 yrs and older) 40 to <80 kg: One 40 mg dose;

>80 kg: One 80 mg dose9
Chemo-prophylaxis8 Not recommended N/A

Abbreviations: N/A = not applicable

1Longer treatment duration may be needed for severely ill patients.
2Oral oseltamivir is approved by the FDA for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in people 14 days and older, and for chemoprophylaxis with once-daily dosing in people 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, 2018).
3This 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 9-11 months old, 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.
4Current 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, 2018): 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.
5See Special Considerations for Institutional Settings section below for details regarding duration of chemoprophylaxis for outbreaks in institutional settings.
6Inhaled zanamivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with twice-daily dosing in people 7 years and older, and for chemoprophylaxis with once-daily dosing in people 5 years and older.
7Intravenous peramivir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with a single dose in people 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).
8There are no data for use of peramivir or baloxavir for chemoprophylaxis of influenza.
9Oral baloxavir is approved for treatment of acute uncomplicated influenza within 2 days of illness onset with a single dose in people 12 years and older who weigh more than 40 kg (Hayden, 2018). Safety and efficacy in patients less than 12 years old or weighing less than 40 kg have not been established. Balaxavir marboxil should not be administered with dairy products, calcium-fortified beverages, polyvalent cation-containing laxatives, antacids or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc); co-administration with polyvalent cation-containing products may decrease plasma concentrations of baloxavir which may reduce efficacy.

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 or oral baloxavir, 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 people 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.
  • Neuraminidase inhibitor antiviral medications are approximately 70% to 90% effective in preventing influenza against susceptible influenza viruses 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 people 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 people receiving immunosuppressive medications, after 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.
  • 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 people.
  • 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 people 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 people 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 site [259 KB, 30 Pages].

 Top of Page

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. The dose of intravenous peramivir should be reduced for patients with baseline creatinine clearance below 50 mL/min (see Table 3).

No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment. Pharmacokinetic analysis did not identify a clinically meaningful effect of renal function on the pharmacokinetics of baloxavir in patients with creatinine clearance 50 mL/min and above. The effects of severe renal impairment on the pharmacokinetics of baloxavir marboxil or its active metabolite, baloxavir, have not been evaluated.

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

1 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.

2 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.

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

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

5 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, intravenous peramivir, or oral baloxavir, visit Antiviral Drugs or consult the package inserts.

Drug Interactions

  • Co-administration of baloxavir with polyvalent cation-containing products may decrease plasma concentrations of baloxavir which may reduce efficacy. Avoid co-administration of baloxavir with polyvalent cation-containing laxatives, antacids, or oral supplements (e.g., calcium, iron, magnesium, selenium, or zinc).
  • Concurrent administration of antiviral drugs with intranasal live attenuated influenza vaccine (LAIV) may inhibit viral replication of LAIV and thereby decrease the effectiveness of LAIV vaccination. Use of LAIV should be avoided within 2 weeks before or 48 hours after administration of influenza antiviral drugs, unless medically indicated.

 

 

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).

 Top of Page

References

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

 Top of Page

Get Email Updates

To receive weekly email updates about Seasonal Flu, enter your email address:

Enter Email AddressWhat's this?Submit
Language:
TOP