Use of Antiviral Medications for the Management of Influenza in Children and Adolescents for the 2009-2010 Season -- Pediatric Supplement for Health Care Providers

Use of Antiviral Medications for the Management of Influenza in Children and Adolescents for the 2009-2010 Season -- Pediatric Supplement for Health Care Providers

Objective
To provide supplemental recommendations for health care providers of children and adolescents on the use of antiviral medications for the treatment and chemoprophylaxis of influenza including 2009 H1N1 influenza infection and seasonal influenza, and assist clinicians in prioritizing use of antiviral medications for hospitalized patients and those at higher risk for influenza-related complications. These recommendations highlight issues specific to children and adolescents and are based on current recommendations for antiviral use (http://www.cdc.gov/h1n1flu/recommendations.htm) and influenza diagnostic testing recommendations (http://www.cdc.gov/h1n1flu/guidance/diagnostic_tests.htm). These recommendations can be adapted according to local epidemiologic data, antiviral susceptibility patterns, and antiviral supply considerations. These recommendations may be further revised if changes in the clinical presentation or antiviral susceptibility of 2009 H1N1 influenza are observed. Additional information about these recommendations can be found in Questions and Answers: Revised Recommendations for the Use of Influenza Antiviral Drugs at http://www.cdc.gov/h1n1flu/antiviral.htm

Background
Based on global experience to date, 2009 H1N1 influenza viruses will likely be the most common circulating influenza viruses this season, particularly among those causing influenza in younger age groups. However, circulation of seasonal influenza viruses during the 2009-10 season also is likely. Health care providers should consult their hospital or local, state, or national surveillance data regularly to determine the current pattern of circulating influenza viruses as well as co-circulation of other respiratory viruses, such as respiratory syncytial virus. Information on influenza activity and surveillance can be found at http://www.cdc.gov/flu/weekly/. These considerations, in addition to the ones below, should guide clinical decision-making and therapy.

Considerations for antiviral therapy
Influenza antiviral medications can reduce the severity and duration of influenza illness and can reduce the risk of influenza-related complications, including severe illness and death.

Most children and adolescents who develop a mild illness consistent with uncomplicated influenza, or appear to be recovering from influenza, do not need antiviral medications for treatment. However, clinical judgment is always an essential part of treatment decisions. Assessment of a child’s or adolescent’s clinical presentation and underlying risk factors for influenza-related complications and death should guide medical decisions regarding evaluation, follow-up, or treatment.

Prompt empiric antiviral therapy with oseltamivir (Tamiflu®) or zanamivir (Relenza®)1 is recommended for children and adolescents of any age presenting with suspected or confirmed influenza and
severe illness, or
evidence of clinical deterioration regardless of previous health, or
symptoms of lower respiratory tract involvement, or
illness requiring hospitalization.
Treatment should not wait for laboratory confirmation of influenza because waiting for laboratory testing results can delay treatment and because a negative rapid test for influenza does not rule out influenza.
Treatment, when indicated, should be initiated as early as possible because the benefits are greatest when started within the first 2 days of illness. However, some studies of hospitalized patients with seasonal and 2009 H1N1 influenza have suggested benefit of antiviral treatment even when treatment was started more than 48 hours after illness onset.
Infants have had higher rates of hospitalization and death from 2009 H1N1 influenza infections compared with other age groups. The FDA has authorized oseltamivir for the treatment of 2009 H1N1 influenza infections in children younger than 1 year old, under an Emergency Use Authorization (EUA) 2.
Early outpatient empiric treatment with oseltamivir or zanamivir should be considered for children and adolescents with suspected or confirmed influenza who are at higher risk for complications including:
Children younger than 2 years old (Please see below for special considerations for treatment or chemoprophylaxis of children younger than 1 year old);
Children and adolescents with certain chronic medical or immunosuppressive conditions including:
Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), or metabolic disorders (including diabetes mellitus);
Disorders that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration (e.g., cognitive dysfunction, spinal cord injuries; epilepsy, or other neuromuscular disorders);
Immunosuppression, including that caused by medications or by HIV;
Pregnant adolescents and adolescents up to 2 weeks postpartum (including following pregnancy loss);
Persons younger than 19 years old who are receiving long-term aspirin therapy, because of an increased risk for Reye syndrome.
Children 2-4 years old are more likely to require urgent medical evaluation or hospitalization due to influenza compared with older children, although the risk is lower than for children < 2 years old.
The American Academy of Pediatrics has developed a document that describes underlying medical conditions in children that appear to be the highest risk for mortality from 2009 H1N1 influenza infection. http://www.aap.org/new/AAP-Work-Group-CSHCN-H1N1-FINAL-10-1-09.pdf

In October 2009, monovalent inactivated and live attenuated 2009 H1N1 influenza vaccines became available in the United States. These vaccines are prepared using methods similar to those used for seasonal influenza vaccines and are licensed for persons > 6 months old. Although these vaccines are expected to be highly effective, no vaccine is 100% efficacious. Therefore, a history of receipt of 2009 H1N1 or seasonal influenza vaccine does not rule out influenza infection. Early empiric treatment should be initiated for vaccinated persons with suspected influenza infection when indicated (e.g., persons requiring hospitalization, with severe infection, or at higher risk for influenza-related complications). Vaccination with 2009 H1N1 influenza vaccine is not expected to provide protection against infection with seasonal influenza A or B viruses. Similarly, vaccination with seasonal influenza vaccine is not expected to prevent infection with 2009 H1N1 influenza virus.

Ensuring early treatment

Treatment, when indicated, should be initiated as early as possible because the benefits are greatest when started within the first 2 days of illness. However, some studies of hospitalized patients with seasonal and 2009 H1N1 influenza have suggested benefit of antiviral treatment even when treatment was started more than 48 hours after illness onset.
Treatment should not wait for laboratory confirmation of influenza because waiting for laboratory testing results can delay treatment and because a negative rapid test for influenza does not rule out influenza. The sensitivity of rapid tests can range from 10% to 70%. Information on influenza diagnostic testing can be found at http://www.cdc.gov/h1n1flu/guidance/diagnostic_tests.htm.
Testing for 2009 H1N1 influenza infection with real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) should be prioritized for persons with suspected or confirmed influenza requiring hospitalization and based on guidelines from local and state health departments. Updated influenza diagnostic testing recommendations are available at http://www.cdc.gov/h1n1flu/guidance/diagnostic_tests.htm.
Because rapid access to antiviral medications is essential, health care providers who care for children and adolescents at higher risk for influenza complications should develop methods to ensure that treatment can be started quickly after symptom onset. Actions that should be taken to reduce delays in treatment initiation include:
Informing caretakers of children and adolescents at higher risk for influenza complications of influenza signs and symptoms3 and the need for early treatment after onset of symptoms.
Ensuring rapid access to telephone consultation and clinical evaluation for children and adolescents at higher risk for influenza complications or who report severe illness.
Based on telephone consultation, health care providers can recommend appropriate follow-up (e.g., immediate medical care or outpatient follow-up).

Pharmaceutical considerations
Antiviral dosage can be determined by age and weight (Table 1); for uncomplicated influenza infections, the duration of antiviral treatment is 5 days. Hospitalized patients with severe infections (such as those with prolonged infection or who require intensive care unit admission) might require longer treatment courses.
Oseltamivir (Tamiflu®) 75 mg capsules can be compounded at most retail pharmacies into a suspension when commercially manufactured Tamiflu® oral suspension is not available. Health care providers can suggest this compounding alternative when writing prescriptions for Tamiflu® oral suspension. Tamiflu® oral suspension concentration is 12 mg/mL; the compounded suspension concentration is 15 mg/mL. For more information, http://www.cdc.gov/H1N1flu/pharmacist/pharmacist_info.htm.
Health care providers should be aware that an oral dosing dispenser packaged with the Tamiflu® oral suspension is in milligram (mg) graduations rather than in milliliters (mL) or teaspoons (tsp). If the units of measure on the prescription dosing instructions (mL, tsp) do not match the units on the dosing device (mg), there is potential for confusion and dosing errors. For more information, http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm183649.htm
The U.S. Food and Drug Administration has issued an Emergency Use Authorizations (EUAs) to make available Tamiflu® (oseltamivir) and Relenza® (zanamivir) to respond to the flu virus under certain circumstances.
For general EUA information, please see http://www.cdc.gov/h1n1flu/eua/.
For additional fact sheets for health care providers for these products, please see http://www.cdc.gov/h1n1flu/eua/tamiflu.htm and http://www.cdc.gov/h1n1flu/eua/relenza.htmSupportive care

Aspirin or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) should not be administered to any confirmed or suspected ill case of influenza aged 18 years old and younger due to the risk of Reye syndrome. For relief of fever, other anti-pyretic medications such as acetaminophen or non-steroidal anti-inflammatory drugs are recommended.
Children younger than 4 years old should not be given over-the-counter cold medications without first speaking with a health care provider.
Antiviral resistance

As of October 2009, circulating 2009 H1N1 influenza viruses are susceptible to oseltamivir and zanamivir, but resistant to amantadine and rimantadine. Updated information on influenza antiviral resistance can be found at http://www.cdc.gov/flu/weekly/.
Bacterial coinfections

Clinicians are also reminded to consider the possibility of bacterial coinfections that can occur during or after an influenza illness.
Considerations for post-exposure chemoprophylaxis
Chemoprophylaxis generally should not be used for prevention of illness among healthy children and adolescents after exposures in community, school, camp, or other settings. When mass chemoprophylaxis has been used in healthy children and adolescents in these settings, sporadic cases of oseltamivir resistant 2009 H1N1 influenza viruses have developed (http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5835a1.htm).
Infected persons may shed influenza virus, and potentially be infectious to others, beginning one day before they develop symptoms to up to 7 days after they become ill. Children, especially younger children, and persons who are immune compromised can shed influenza virus for longer periods. However, the amount of virus shed generally correlates with magnitude of fever. For these recommendations, the infectious period for influenza is defined as one day before until 24 hours after fever ends (without the use of fever reducing medications).
Post-exposure chemoprophylaxis may be indicated in certain situations if contact occurred during the ill person’s infectious period and it has been less than 48 hours since the last contact with the infectious person.
Post-exposure antiviral chemoprophylaxis generally should be reserved for children and adolescents at higher risk for complications from influenza (see list above) who have had contact with someone likely to have been infectious with influenza.
Early evaluation and treatment is an emphasized alternative to chemoprophylaxis after a suspected exposure for children and adolescents at higher risk for complications from influenza. Caregivers of children or adolescents who are at higher risk for complications from influenza and who are household or close contacts of suspected or confirmed cases can be counseled about the early signs and symptoms of influenza, and advised to immediately contact the children’s or adolescents’ health care provider for evaluation and possible early treatment if clinical signs or symptoms develop in children or adolescents.
Early evaluation and treatment is preferred to chemoprophylaxis among healthy vaccinated children and adolescents after a suspected exposure.
Caregivers of children or adolescents should be informed that post-exposure chemoprophylaxis lowers but does not eliminate the risk for influenza and that protection stops when the medication course is stopped.
The duration of antiviral chemoprophylaxis post-exposure is 10 days after the last known exposure. See Table 1 for dosing information; note that zanamivir chemoprophylaxis can be used for children 5 years or older.
Oseltamivir chemoprophylaxis for influenza virus infection in children younger than 1 year old is age-based; however, chemoprophylaxis for asymptomatic infants less than 3 months old is not recommended due to lack of safety data.
If early signs and symptoms of influenza occur in children or adolescents receiving post-exposure chemoprophylaxis, the person should be clinically evaluated to determine if the dosage of antiviral chemoprophylaxis might need to be increased to the therapeutic dose and if evaluation for other respiratory pathogens is indicated.
Links to CDC recommendations regarding 2009 H1N1 influenza in children and adolescents:
Antiviral treatment: Antiviral Recommendations Sep 22
Influenza Diagnostic Testing: Interim Recommendations for Clinical Use of Influenza Diagnostic Tests During the 2009-10 Influenza Season Sep 29

Child Care settings: http://www.cdc.gov/h1n1flu/childcare/
K-12 Schools: http://www.cdc.gov/h1n1flu/schools/
Colleges and Universities: http://www.cdc.gov/h1n1flu/institutions/

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Use of Antiviral Medications for the Management of Influenza in Children and Adolescents for the 2009-2010 Season -- Pediatric Supplement for Health Care Providers