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Guideline Summary
Guideline Title
Antiviral agents for the treatment and chemoprophylaxis of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP).
Bibliographic Source(s)
Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM, Centers for Disease Control and Prevention (CDC). Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Surveill Summ. 2011 Jan 21;60(1):1-24. [234 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NS, Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep 2008 Aug 8;57(RR-7):1-60.

Further updates, if needed, will be posted at Center for Disease Control and Prevention's (CDC's) influenza website (http://www.cdc.gov/flu External Web Site Policy).

Scope

Disease/Condition(s)

Influenza

Guideline Category
Diagnosis
Management
Prevention
Risk Assessment
Treatment
Clinical Specialty
Allergy and Immunology
Family Practice
Geriatrics
Infectious Diseases
Internal Medicine
Obstetrics and Gynecology
Pediatrics
Pharmacology
Preventive Medicine
Intended Users
Advanced Practice Nurses
Allied Health Personnel
Emergency Medical Technicians/Paramedics
Health Care Providers
Hospitals
Nurses
Physician Assistants
Physicians
Public Health Departments
Guideline Objective(s)

To update previous recommendations by the Centers for Disease Prevention and Control (CDC) Advisory Committee on Immunization Practices (ACIP) regarding the use of antiviral agents for the prevention and treatment of influenza

Target Population

All persons, with emphasis placed on the following:

  • Persons at higher risk for influenza complications, include:
    • Children aged <5 years (especially those aged <2 years)
    • Adults aged ≥65 years
    • Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematologic (including sickle cell disease), 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 human immunodeficiency virus (HIV) infection
    • Women who are pregnant or postpartum (within 2 weeks after delivery)
    • Persons aged ≤18 years who are receiving long-term aspirin therapy
    • American Indians/Alaska Natives
    • Persons who are morbidly obese (i.e., body mass index [BMI] ≥40)
    • Residents of nursing homes and other chronic-care facilities
Interventions and Practices Considered

Antiviral agents for influenza:

  • Zanamivir
  • Oseltamivir
  • Amantadine
  • Rimantadine

Note: Amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A virus strains.

Major Outcomes Considered
  • Influenza-related morbidity and mortality rates
  • Influenza-related hospitalization rates
  • Antiviral drug resistance rates
  • Side effects and adverse events of antiviral agents

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Searches of Unpublished Data
Description of Methods Used to Collect/Select the Evidence

Not stated

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Not stated
Rating Scheme for the Strength of the Evidence

Not applicable

Methods Used to Analyze the Evidence
Review
Description of the Methods Used to Analyze the Evidence

Not stated

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The Centers for Disease Prevention and Control (CDC) Advisory Committee on Immunization Practices (ACIP) provides annual recommendations for the prevention and control of influenza. The ACIP Influenza Work Group meets monthly throughout the year to discuss newly published studies, review current guidelines, and consider potential revisions to the recommendations. As they review the annual recommendations for consideration of the full ACIP, members of the Work Group consider a variety of issues, including burden of influenza illness, vaccine efficacy and effectiveness, safety and coverage in groups recommended for vaccination, feasibility, cost-effectiveness, and anticipated vaccine supply. Work group members also request periodic updates on antiviral production, supply, safety, efficacy, and effectiveness from clinician researchers, regulatory agencies, public health epidemiologists, and manufacturers and review influenza surveillance and antiviral resistance data obtained from CDC's Influenza Division.

Published, peer-reviewed studies are the primary source of data used by ACIP in making recommendations for the prevention and control of influenza, but unpublished data that are relevant to issues under discussion also are considered. The best evidence for antiviral efficacy comes from randomized, controlled trials that assess laboratory-confirmed influenza virus infection as an outcome measure. However, randomized, placebo-controlled trials might be difficult to perform in populations for which antiviral treatment already is recommended. Observational studies that assess outcomes associated with laboratory-confirmed influenza virus infection can provide important antiviral effectiveness data but are more subject to biases and confounding that can affect validity and the size of effects measured. Randomized, placebo-controlled clinical trials are the best source of antiviral safety data for common adverse events; however, such studies do not have the power to identify rare but potentially serious adverse events. In cited studies that included statistical comparisons, a difference was considered to be statistically significant if the p-value was <0.05 or the 95% confidence interval around an estimate of effect allowed rejection of the null hypothesis (i.e., no effect).

Rating Scheme for the Strength of the Recommendations

Not applicable

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation

These recommendations were presented to the full Advisory Committee on Immunization Practices (ACIP) and approved in June 2009. Modifications were made to the ACIP statement during the subsequent review process at the Centers of Disease Prevention and Control (CDC) to update and clarify wording in the document.

Recommendations

Major Recommendations

Primary Changes and Updates in the Recommendations

These recommendations include six principal changes or updates from previous recommendations for use of antivirals for the prevention and control of influenza:

  • Antiviral treatment is recommended as soon as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness or who require hospitalization.
  • Antiviral treatment is recommended as soon as possible for outpatients with confirmed or suspected influenza who are at higher risk for influenza complications on the basis of their age or underlying medical conditions; clinical judgment should be an important component of outpatient treatment decisions.
  • Recommended antiviral medications include oseltamivir and zanamivir, on the basis of recent viral surveillance and resistance data indicating that >99% of currently circulating influenza virus strains are sensitive to these medications. Amantadine and rimantadine should not be used because of the high levels of resistance to these drugs among circulating influenza A viruses, but information about these drugs is provided for use if current recommendations change because of the reemergence of adamantane-susceptible strains.
  • Oseltamivir may be used for treatment or chemoprophylaxis of influenza among infants aged <1 year when indicated.
  • Antiviral treatment also may be considered on the basis of clinical judgment for any outpatient with confirmed or suspected influenza who does not have known risk factors for severe illness if treatment can be initiated within 48 hours of illness onset.
  • Because antiviral resistance patterns can change over time, clinicians should monitor local antiviral resistance surveillance data.

Antiviral Agents for Influenza

Four licensed prescription influenza antiviral agents are available in the United States: amantadine, rimantadine, zanamivir, and oseltamivir. Zanamivir and oseltamivir are related antiviral medications in a class of medications known as neuraminidase inhibitors. These two medications are active against both influenza A and B viruses. They differ in pharmacokinetics, safety profiles, routes of administration, approved age groups, and recommended dosages (see Table 1 in the original guideline document).

Amantadine and rimantadine are related antiviral drugs in a class of medications known as adamantanes. These medications are active against influenza A viruses but not influenza B viruses. In recent years, widespread adamantane resistance among influenza A (H3N2) virus strains has made this class of medications less useful clinically. In addition, circulating 2009 H1N1 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.

Use of Antivirals

Treatment Indications

Clinical judgment based on underlying conditions, disease severity, and time since symptom onset are also important factors in treatment decisions. Antiviral treatment is recommended as soon as possible for all persons with suspected or confirmed influenza requiring hospitalization or who have progressive, severe or complicated illness regardless of previous health or vaccination status. In observational studies conducted among severely ill patients, both early initiation of antiviral treatment (<2 days from illness onset) and treatment up to <5 days after onset were associated with reduced morbidity and mortality, with greater benefit associated with earlier initiation of treatment. Additional research is needed to better assess the impact of treatment, but on the basis of these limited data, treatment of severely ill patients as soon as possible is strongly recommended. Treatment should not be delayed while the results of diagnostic testing are awaited (see Box below). Empiric antiviral treatment is often necessary, and providers should not delay initiation of treatment while awaiting confirmatory diagnostic tests results or if specimens are not obtained. Patients with suspected influenza should complete antiviral treatment for a full treatment course regardless of negative initial test results unless an alternative diagnosis can be established and clinical judgment suggests that influenza is unlikely.

BOX. Summary of Influenza Antiviral Treatment Recommendations
  • Early antiviral treatment can reduce the risk of complications from influenza (e.g., pneumonia, respiratory failure, and death). 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
    • Is at higher risk for influenza complications.
  • Persons at higher risk for influenza complications recommended for antiviral treatment include:
    • Children aged <2 years*
    • Adults aged ≥65 years
    • Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), 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 human immunodeficiency virus (HIV) infection
    • Women who are pregnant or postpartum (within 2 weeks after delivery)
    • Persons aged <19 years who are receiving long-term aspirin therapy
    • American Indians/Alaska Natives
    • Persons who are morbidly obese (i.e., body-mass index ≥40)
    • 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 to consider when making antiviral treatment decisions for high-risk outpatients. When indicated, antiviral treatment should be started as soon as possible after illness onset.
  • The greatest benefit is when antiviral treatment is started within 48 hours of influenza illness onset. However, antiviral treatment might still be beneficial in patients with severe, complicated, or progressive illness and in hospitalized patients when administered >48 hours from illness onset.
  • 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.†

* Although all children aged <5 years are considered at higher risk for complications from influenza, the highest risk is for those aged <2 years, with the highest hospitalization and death rates among infants aged <6 months. Because many children with mild febrile respiratory illness might have other viral infections (e.g., respiratory syncytial virus, rhinovirus, or parainfluenza virus, or human metapneumovirus), knowledge about other respiratory viruses as well as influenza virus strains circulating in the community is important for treatment decisions. The likelihood of influenza virus infection in a patient depends on the prevalence of influenza activity in the local community and on the patient's signs and symptoms. Information about influenza activity in the United States during the influenza season is available at http://www.cdc.gov/flu/weekly External Web Site Policy For information on local community influenza activity, clinicians should contact their local and state health departments.

† Recommended antiviral medications (neuraminidase inhibitors) are not licensed for treatment of children aged <1 year (oseltamivir) or those aged <7 years (zanamivir). Oseltamivir was used for treatment of 2009 pandemic influenza A (H1N1) virus infection in children aged <1 year under an Emergency Use Authorization, which expired on June 23, 2010. Limited information regarding use of oseltamivir for children from birth through age 1 year is available (see Table 4 in the original guideline document). Confirmation of influenza virus infection may be performed by different influenza testing methods. Information on influenza testing is available at http://www.cdc.gov/flu/professionals/diagnosis/index.htm External Web Site Policy. In areas with limited antiviral medication availability, local public health authorities might provide additional guidance about prioritizing treatment within groups at higher risk for complications. Current Centers for Disease Control and Prevention (CDC) guidance on treatment of influenza should be consulted; updated recommendations from CDC are available at http://www.cdc.gov/flu External Web Site Policy.

Among outpatients, antiviral treatment with a neuraminidase inhibitor is recommended for all persons with suspected or confirmed influenza who are at higher risk for influenza complications because of age or underlying medical conditions (see Box, above). Although all children aged <5 years are considered at higher risk for complications from influenza, the highest risk is for those aged <2 years, with the highest hospitalization and death rates among infants aged <6 months. On the basis of epidemiologic studies of patients with seasonal influenza or 2009 H1N1, persons at higher risk for influenza complications who are recommended for antiviral treatment for suspected or confirmed influenza include:

  • Children aged <2 years
  • Adults aged ≥65 years
  • Persons with chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), 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 <19 years who are receiving long-term aspirin therapy
  • American Indians/Alaska Natives
  • Persons who are morbidly obese (i.e., body mass index [BMI] ≥40)
  • Residents of nursing homes and other chronic-care facilities

Some treatment recommendations from other expert advisory groups are more definite about the need to treat all persons at higher risk for influenza complications who are suspected of having influenza, especially if the suspected cause is 2009 H1N1 virus infection. The World Health Organization (WHO) has recommended empiric neuraminidase inhibitor treatment for all persons with suspected or confirmed 2009 H1N1 virus infection who are at increased risk for influenza complications, and similar recommendations were made by the Centers for Disease Control and Prevention (CDC) during the 2009 H1N1 pandemic and the subsequent 2009 to 2010 influenza season. The Infectious Diseases Society of America (IDSA) recommends that all persons with laboratory-confirmed or highly suspected influenza virus infection who are at high risk for developing complications receive treatment, when treatment can begin within 48 hours after symptom onset. Clinicians who prefer not to treat empirically should discuss signs and symptoms of worsening illness with such patients and arrange for follow up by telephone or in the clinic. Options for close follow-up should be considered carefully.

Clinicians should monitor local, state, and national recommendations during the influenza season to determine the most appropriate treatment practices and receive updates on antiviral resistance profiles of the circulating viruses (see Table 3 in the original guideline document). Treatment options could become complicated if oseltamivir-resistant seasonal influenza A (H1N1) virus strains that circulated during 2007 to 2009 reappear or if neuraminidase inhibitor resistance becomes more common among circulating H3N2 or 2009 H1N1 virus strains. The lack of influenza A virus subtyping and antiviral resistance testing availability in most settings might present additional challenges in determining optimal antiviral therapy if oseltamivir resistance among circulating influenza virus strains becomes more prevalent.

The benefits of antiviral treatment are likely to be greatest if treatment is started as soon as possible after illness onset, and evidence for benefit is strongest in studies in which treatment was started within 48 hours of illness onset. However, treatment of any person with confirmed or suspected influenza who requires hospitalization is recommended, even if the patient presents >48 hours after illness onset. Patients with influenza are at high risk for such secondary bacterial complications as bacterial pneumonia. Antibacterial therapy plus antiviral treatment are recommended for patients with community-acquired pneumonia when influenza also is suspected. Antibiotic treatment should be directed at likely bacterial pathogens associated with influenza such as Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus, including methicillin-resistant (MRSA), especially for hospitalized patients. Clinicians should consider influenza virus infection as the possible cause of any febrile respiratory illness requiring hospitalization during influenza season and consider testing for influenza and starting empiric antiviral therapy.

Treatment also can be considered, on the basis of clinical judgment, for outpatients with uncomplicated, suspected, or confirmed influenza who are not known to be at increased risk for developing severe or complicated illness if antiviral treatment can be initiated within 48 hours of illness onset. Persons with influenza who present with an uncomplicated febrile illness typically do not require treatment unless they are at higher risk for influenza complications, but early empiric antiviral treatment of these patients also might provide benefit (e.g., a shortened duration of illness). Persons with influenza who are already beginning to recover do not need to start treatment. Treatment decisions, especially those involving empiric treatment, should be informed by knowledge of influenza activity in the community. Empiric treatment for febrile respiratory illness when influenza activity in the community is low is likely to result in a large proportion of persons without influenza receiving unnecessary influenza antivirals. In addition, patients not at increased risk for developing severe or complicated illness and who have mild, uncomplicated illness are less likely to benefit from treatment if initiated more than 48 hours after illness onset.

Postexposure Chemoprophylaxis Indications

Clinical judgment and advice from local authorities are important factors in making postexposure chemoprophylaxis decisions. Decisions on whether to administer antivirals for chemoprophylaxis should take into account the exposed person's risk for influenza complications, the type and duration of contact, recommendations from local or public health authorities, and clinical judgment. Generally, postexposure chemoprophylaxis for persons should be only used when antivirals can be started within 48 hours of the most recent exposure. In areas with limited antiviral medication availability, local public health authorities might provide additional guidance about prioritizing chemoprophylaxis within groups at higher risk for complications. In certain situations, CDC or local public health authorities might recommend that antiviral medication resources be primarily directed at treatment and that antiviral chemoprophylaxis be used only in certain limited situations.

Chemoprophylaxis with antiviral medications is not a substitute for influenza vaccination when influenza vaccine is available. Adverse events associated with antiviral medications are generally mild and self-limited but might result in morbidity resulting from medication side effects that outweigh the potential benefit of antiviral chemoprophylaxis. In addition, indiscriminate use of chemoprophylaxis might promote resistance to antiviral medications or reduce antiviral medication availability for treatment of persons at higher risk for influenza complications or who are severely ill.

Patients receiving postexposure antiviral chemoprophylaxis should be informed that chemoprophylaxis lowers but does not eliminate the risk for influenza, that susceptibility to influenza returns once the antiviral medication is stopped, and that influenza vaccination is recommended if available. Patients receiving chemoprophylaxis should be encouraged to seek medical evaluation as soon as they develop a febrile respiratory illness suggestive of influenza because influenza virus infection still can occur while a patient is on chemoprophylaxis and might indicate infection with a virus resistant to the antiviral medication used. Either oseltamivir or zanamivir is recommended for antiviral chemoprophylaxis of 2009 H1N1, influenza A (H3N2), or influenza B influenza virus infection (see Table 1 in the original guideline document).

An emphasis on early treatment is an alternative to chemoprophylaxis in managing certain persons who have had a suspected exposure to influenza virus. Persons with risk factors for influenza complications who are household or close contacts of persons with confirmed or suspected cases and health-care personnel who have occupational exposures can be counseled about the early signs and symptoms of influenza and advised to contact their health-care provider immediately for evaluation and possible early treatment if clinical signs or symptoms develop. Health-care providers should use clinical judgment regarding situations in which early recognition of illness and treatment might be an appropriate alternative. In some exposure circumstances (e.g., when the person exposed is at higher risk for complications of influenza virus infection), health-care providers might choose to give the exposed patient a prescription for an influenza antiviral. Providers may request that the patient contact the provider if signs or symptoms of influenza develop, obtain an antiviral medication as quickly as possible, and initiate treatment. These patients also should be counseled about influenza antiviral medication adverse events and informed that they remain susceptible to influenza virus infection after the antiviral medications are stopped.

Adverse Events

Reporting of Adverse Events that Occur After Administering Antiviral Medications

Health-care professionals should report any serious adverse event after antiviral medication use promptly to MedWatch, the FDA's adverse event reporting program for medications. Serious adverse events are defined as medical events that involve hospitalization, death, life-threatening illness, disability, or certain other medically important conditions. Any serious adverse event that follows administration of medications should be reported to FDA at http://www.fda.gov/medwatch/report/hcp.htm External Web Site Policy.

Additional Recommendations

See the original guideline document for recommendations on the following:

  • Treatment issues for patients hospitalized with suspected or confirmed influenza
  • Preexposure chemoprophylaxis
  • Duration of chemoprophylaxis
  • Considerations for antiviral use if oseltamivir-resistant virus strains are circulating
  • Considerations for antiviral use when antiviral supplies are limited
  • Control of influenza outbreaks in institutions
  • Dosage information in populations including adults; children; persons aged ≥65 years; pregnant women; and persons with impaired renal function, liver disease, seizure disorders, or immunosuppression
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is not specifically stated for each recommendation.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate use of antiviral agents used for the treatment and chemoprophylaxis of influenza

Potential Harms

Antiviral Drug Resistance

Indiscriminate use of chemoprophylaxis might promote resistance to antiviral medications or reduce antiviral medication availability for treatment of persons at higher risk for influenza complications or who are severely ill.

Persons with Seizure Disorders

Zanamivir and Oseltamivir

Seizure events have been reported during postmarketing use of zanamivir and oseltamivir, although no epidemiologic studies have reported any increased risk for seizures with either zanamivir or oseltamivir use.

Adverse Events

The adverse events associated with long-term antiviral use are uncertain, and prolonged use of antivirals might select for resistance to antiviral medications.

When considering use of influenza antiviral medications (i.e., choice of antiviral drug, dosage, and duration of therapy), clinicians must consider the patient's age, weight, and renal function (see Table 1 in the original guideline document); presence of other medical conditions; indications for use (i.e., chemoprophylaxis or therapy); and the potential for interaction with other medications.

Zanamivir

Limited data are available about the safety or efficacy of zanamivir for persons with underlying respiratory disease or for persons with complications of acute influenza, and zanamivir is licensed only for use in persons without underlying respiratory or cardiac disease. In a study of zanamivir treatment of influenza-like illness (ILI) among persons with asthma or chronic obstructive pulmonary disease in which study medication was administered after use of a beta2-agonist, 13% of patients receiving zanamivir and 14% of patients who received inhaled placebo (powdered lactose vehicle alone) experienced a >20% decline in forced expiratory volume in 1 second (FEV1) after treatment. However, in a phase-I study of persons with mild or moderate asthma who did not have ILI, one of 13 patients experienced bronchospasm after administration of zanamivir. In addition, during postmarketing surveillance, cases of respiratory function deterioration after inhalation of zanamivir have been reported. Because of the risk for serious adverse events and because efficacy has not been demonstrated among this population, zanamivir is not recommended for treatment for patients with underlying pulmonary disease. Allergic reactions, including oropharyngeal or facial edema, also have been reported during postmarketing surveillance.

In clinical treatment studies of persons with uncomplicated influenza, the frequencies of adverse events were similar for persons receiving inhaled zanamivir and for those receiving inhaled placebo (i.e., powdered lactose vehicle alone). The most common adverse events reported by both groups were diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose, and throat infections. Each of these symptoms was reported by <5% of persons in the clinical treatment studies combined. Zanamivir does not impair the immunologic response to trivalent inactivated vaccine.

Oseltamivir

Nausea and vomiting were reported more frequently among adults receiving oseltamivir for treatment (nausea without vomiting: approximately 10%; vomiting: approximately 9%) than among persons receiving placebo (nausea without vomiting: approximately 6%; vomiting: approximately 3%). Among children treated with oseltamivir, 14% had vomiting, compared with 8.5% of placebo recipients. Overall, 1% discontinued the drug secondary to this side effect, and a limited number of adults who were enrolled in clinical treatment trials of oseltamivir discontinued treatment because of these symptoms. Similar types and rates of adverse events were reported in studies of oseltamivir chemoprophylaxis. Nausea and vomiting might be less severe if oseltamivir is taken with food. In several reports based on public health responses to school outbreaks of 2009 H1N1, self-reported nausea and vomiting have been more common than reported in clinical studies and might reduce compliance with recommended treatment or chemoprophylaxis regimens among children. No published studies have assessed whether oseltamivir impairs the immunologic response to trivalent inactivated influenza vaccine.

Transient neuropsychiatric events (self-injury or delirium) have been reported postmarketing among persons taking oseltamivir; the majority of reports were among Japanese adolescents and adults. Several recent analyses and reviews have found that oseltamivir is not associated with an increased risk for neuropsychiatric events. The U.S. Food and Drug Administration (FDA) advises that persons receiving oseltamivir be monitored closely for abnormal behavior.

Limited safety data on oseltamivir treatment for seasonal influenza in children aged <1 year have not demonstrated any age-related safety concerns, but careful attention to dosing is essential. Health-care providers should be aware of the limited data on safety and dosing when considering oseltamivir use for infants, and carefully monitor infants for adverse events. Clinicians and pharmacists should pay careful attention to the potential for dosing errors in young children.

Contraindications

Contraindications

Because of the risk for serious adverse events and because efficacy has not been demonstrated among this population, zanamivir is not recommended for treatment for patients with underlying pulmonary disease.

Qualifying Statements

Qualifying Statements
  • Recommendations in this report do not necessarily represent U.S. Food and Drug Administration (FDA)-approved uses of antiviral products but are based on published expert opinion and observational studies and are subject to change as the developmental status of investigational products and the epidemiologic and virologic features of influenza change over time.
  • Recommended antiviral medications (neuraminidase inhibitors) are not licensed for treatment of children aged <1 year (oseltamivir) or those aged <7 years (zanamivir).
  • Treatment regimens for hospitalized patients might need to be altered to fit the clinical circumstances. For example, clinical judgment should be the guide regarding the need to extend treatment regimens longer than 5 days for patients whose illness is prolonged.
  • Oseltamivir, zanamivir, rimantadine, and amantadine are "Pregnancy Category C" medications, indicating that data from clinical studies are not adequate to assess the safety of these medications for pregnant women.
  • Use of trade names and commercial sources is for identification only and does not imply endorsement by the U.S. Department of Health and Human Services.
  • References to non-Centers for Disease Control and Prevention (CDC) sites on the Internet are provided as a service to Morbidity and Mortality Weekly Report (MMWR) readers and do not constitute or imply endorsement of these organizations or their programs by CDC or the U.S. Department of Health and Human Services. CDC is not responsible for the content of pages found at these sites. URL addresses listed in MMWR were current as of the date of publication.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Foreign Language Translations
Patient Resources
Quick Reference Guides/Physician Guides
Resources
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Staying Healthy
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM, Centers for Disease Control and Prevention (CDC). Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Surveill Summ. 2011 Jan 21;60(1):1-24. [234 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
1984 Apr (revised 2011 Jan 21)
Guideline Developer(s)
Centers for Disease Control and Prevention - Federal Government Agency [U.S.]
Source(s) of Funding

United States Government

Guideline Committee

Advisory Committee on Immunization Practices (ACIP)

Composition of Group That Authored the Guideline

Prepared By: Anthony E. Fiore, MD, Influenza Division, National Center for Immunization and Respiratory Diseases; Alicia Fry, MD, Influenza Division, National Center for Immunization and Respiratory Diseases; David Shay, MD, Influenza Division, National Center for Immunization and Respiratory Diseases; Larisa Gubareva, PhD, Influenza Division, National Center for Immunization and Respiratory Diseases; Joseph S. Bresee, MD, Influenza Division, National Center for Immunization and Respiratory Diseases; Timothy M. Uyeki, MD, Influenza Division, National Center for Immunization and Respiratory Diseases

Advisory Committee on Immunization Practices

Membership List, June 2010

Chair: Carol Baker, MD, Baylor College of Medicine, Houston, Texas

Executive Secretary: Larry Pickering, MD, National Center for Immunization and Respiratory Diseases, CDC, Atlanta, Georgia

Members: Lance Chilton, MD, University of New Mexico, Albuquerque, New Mexico; Paul Cieslak, MD, Oregon Public Health Division, Portland, Oregon; Kristen Ehresmann, MPH, Minnesota Department of Health, St. Paul, Minnesota; Janet Englund, MD, University of Washington and Children's Hospital and Regional Medical Center, Seattle, Washington; Franklyn Judson, MD, University of Colorado Health Sciences Center, Denver, Colorado; Wendy Keitel, MD, Baylor College of Medicine, Houston, Texas; Susan Lett, MD, Massachusetts Department of Public Health, Boston, Massachusetts; Michael Marcy, MD, UCLA Center for Vaccine Research, Torrance, California; Cody Meissner, MD, Tufts Medical Center, Boston, Massachusetts; Kathleen Neuzil, MD, University of Washington, Seattle, Washington; Sara Rosenbaum, JD, Georgetown University, District of Columbia; Mark Sawyer, MD, University of California-San Diego, California; Ciro Valent Sumaya, MD, Texas A&M Health Science Center, College Station, Texas; Jonathan Temte, MD, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin

Ex Officio Members: James E. Cheek, MD, Indian Health Service, Albuquerque, New Mexico; Wayne Hachey, DO, Department of Defense, Falls Church, Virginia; Ted Cieslak, MD, Department of Defense, Atlanta, Georgia; Geoffrey S. Evans, MD, Health Resources and Services Administration, Rockville, Maryland; Bruce Gellin, MD, National Vaccine Program Office, Washington, District of Columbia; Linda Murphy, Centers for Medicare and Medicaid Services, Baltimore, Maryland; George T. Curlin, MD, National Institutes of Health, Bethesda, Maryland; Norman Baylor, PhD, Food and Drug Administration, Bethesda, Maryland; Linda Kinsinger, MD, Department of Veterans Affairs, Durham, North Carolina

Liaison Representatives: American Academy of Family Physicians, Doug Campos-Outcalt, MD, Phoenix, Arizona; American Academy of Pediatrics, Joseph Bocchini, MD, Shreveport, Louisiana, David Kimberlin, MD, Birmingham, Alabama; American College Health Association, James C. Turner, MD, Charlottesville, Virginia; American College of Obstetricians and Gynecologists, Stanley Gall, MD, Louisville, Kentucky; American College of Physicians, Gregory Poland, MD, Rochester, Minnesota; American Geriatrics Society, Kenneth Schmader, MD, Durham, North Carolina; America's Health Insurance Plans, Mark Netoskie, MD, MBA, Houston, Texas; American Medical Association, Litjen Tan, PhD, Chicago, Illinois; American Osteopathic Association, Stanley Grogg, DO, Tulsa, Oklahoma; American Pharmacists Association, Stephan L. Foster, PharmD, Memphis, Tennessee; Association for Prevention Teaching and Research, W. Paul McKinney, MD, Louisville, Kentucky; Biotechnology Industry Organization, Clement Lewin, PhD, Cambridge, Massachusetts; Canadian National Advisory Committee on Immunization, Joanne Langley, MD, Halifax, Nova Scotia, Canada; Council of State and Territorial Epidemiologists, Christine Hahn, MD, Boise, Idaho; Department of Health, United Kingdom David M. Salisbury, MD, London, United Kingdom; Healthcare Infection Control Practices Advisory Committee, Alexis Elward, MD, St Louis, Missouri; Infectious Diseases Society of America, Samuel L. Katz, MD, Durham, North Carolina; National Association of County and City Health Officials, Jeff Duchin, MD, Seattle, Washington; National Association of Pediatric Nurse Practitioners, Patricia Stinchfield, MPH, St Paul, Minnesota; National Foundation for Infectious Diseases, William Schaffner, MD, Nashville, Tennessee; National Immunization Council and Child Health Program, Mexico, Vesta Richardson, MD, Mexico City, Mexico; National Medical Association, Patricia Whitley-Williams, MD, New Brunswick, New Jersey; National Vaccine Advisory Committee, Guthrie Birkhead, MD, Albany, New York; Pharmaceutical Research and Manufacturers of America, Damian A. Braga, Swiftwater, Pennsylvania, Peter Paradiso, PhD, Collegeville, Pennsylvania; Society for Adolescent Medicine, Amy Middleman, MD, Houston, Texas; Society for Healthcare Epidemiology of America, Harry Keyserling, MD, Atlanta, Georgia

ACIP Influenza Vaccine Work Group

Chair: Wendy Keitel, MD, Houston, Texas

Members: William Atkinson, MD, Atlanta, Georgia; Carol Baker, MD, Houston, Texas; Beth Bell, MD, Atlanta, Georgia, Nancy Bennett, MD, Rochester, New York; Henry Bernstein, DO, Lebanon, New Hampshire; Joseph Bresee, MD, Atlanta, Georgia; Carolyn Bridges, MD, Atlanta, Georgia; Karen Broder, MD, Atlanta, Georgia; Doug Campos-Outcalt, MD, Phoenix, Arizona; Fred Cassels, MD, Rockville, Maryland; Lance Chilton, MD, Albuquerque, New Mexico; David Cho, MD, District of Columbia; Nancy Cox, PhD, Atlanta, Georgia; Therese Cvetkovich, MD, Rockville, Maryland; Sandra Dos Santos Chaves, MD, Atlanta, GA; Jeff Duchin, MD, Seattle, Washington; Janet Englund, MD, Seattle, Washington; Anthony Fiore, MD, Atlanta, Georgia; Sandra Fryhofer, MD, Atlanta, Georgia; Stanley Gall, MD, Louisville, Kentucky; Paul Gargiullo, PhD, Atlanta, Georgia; Steven Gordon, MD, Cleveland, Ohio; Wayne Hachey, DO, Falls Church, Virginia; John Iskander, MD, Atlanta Georgia; Wendy Keitel, MD, Houston, Texas; Elyse Olshen Kharbanda, MD, New York, NY; David Lakey, MD, Austin, Texas; Susan Lett, MD, Boston, Massachusetts; Tamara Lewis, MD, Salt Lake City, Utah; Cynthia Nolletti, MD, Rockville, Maryland; Gregory Poland, MD, Rochester, Minnesota; William Schaffner, MD, Nashville, Tennessee; Robert Schechter, MD, Sacramento, California; Kenneth Schmader, MD, Durham, North Carolina; David Shay, MD, Atlanta, Georgia; Nadine Sicard, MD, Ottawa, Canada; Patricia Stinchfield, St. Paul, Minnesota; Ray Strikas, MD, District of Columbia; Litjen Tan, PhD, Chicago, Illinois; Mary Vernon-Smiley, MD, Atlanta, Georgia; Timothy Uyeki, MD, Atlanta, Georgia; Amanda Zongrone, Atlanta, Georgia

Financial Disclosures/Conflicts of Interest

Not stated

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Fiore AE, Shay DK, Broder K, Iskander JK, Uyeki TM, Mootrey G, Bresee JS, Cox NS, Centers for Disease Control and Prevention (CDC), Advisory Committee on Immunization Practices (ACIP). Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR Recomm Rep 2008 Aug 8;57(RR-7):1-60.

Further updates, if needed, will be posted at Center for Disease Control and Prevention's (CDC's) influenza website (http://www.cdc.gov/flu External Web Site Policy).

Guideline Availability

Electronic copies: Available from the Centers for Disease Control and Prevention (CDC) Web site External Web Site Policy.

Print copies: Available by contacting Timothy Uyeki, MD, Influenza Division, National Center for Immunization and Respiratory Diseases, CDC, 1600 Clifton Road, N.E., MS A-20, Atlanta, GA 30333. Telephone: 404-639-3747; Fax: 404-639-3866; E-mail: tuyeki@cdc.gov.

Availability of Companion Documents

The following are available:

Additional information on antiviral medications is available from the CDC Web site External Web Site Policy.

Patient Resources

The following are available:

Additionally, there are other general information resources on antivirals available from the CDC Web site External Web Site Policy.

Please note: This patient information is intended to provide health professionals with information to share with their patients to help them better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether or not it accurately reflects the original guideline's content.

NGC Status

The original summary was completed by ECRI on July 17, 2000, and updated on October 20, 2000. The original summary was verified by the guideline developer as of January 18, 2001. The summary was updated by ECRI on August 6, 2001, June 12, 2002, May 14, 2003, December 18, 2003, June 15, 2004, October 6, 2004, October 30, 2004, and on December 29, 2004 in response to interim recommendations published by the CDC on December 24, 2004. This NGC summary was updated by ECRI on July 21, 2005. This NGC summary was updated on September 23, 2005, in response to the update issued on September 16, 2005 for the 2005-2006 influenza season. It was updated on January 19, 2006, in response to updated guidelines for the use of antivirals. This NGC summary was updated on July 6, 2006, in response to the recommendations issued on June 28, 2006 for the 2006-2007 influenza season. This summary was updated by ECRI on November 21, 2006 following the FDA advisory on Tamiflu. This NGC summary was updated by ECRI Institute most recently on July 5, 2007. This summary was updated by ECRI Institute on March 10, 2008 following the U.S. Food and Drug Administration (FDA) advisory on Tamiflu (oseltamivir phosphate). This summary was updated by ECRI Institute on April 9, 2008 following the U.S. Food and Drug Administration (FDA) advisory on Relenza (zanamivir). This summary was updated by ECRI Institute on August 25, 2008. This NGC summary was updated by ECRI Institute on April 8, 2011. This summary was updated by ECRI Institute on July 15, 2011 following the U.S. Food and Drug Administration advisory on Tamiflu (oseltamivir phosphate).

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