Clinician Outreach and Communication Activity COCA Conference Call

1. Clinician Outreach and Communication Activity (COCA) Conference Call 2009-2010 Pediatric Influenza Triage Tool Interim and Recommendations for the Use of Antiviral Medications for the 2009 � 2010 Influenza Season October 20, 2009

2. 2009-2010 Pediatric Influenza Triage Tool A.J. Kallen, MD, MPH Division of Healthcare Quality Promotion Centers for Disease Control and Prevention

11. Address: http://www.cdc.gov/h1n1flu/clinicians/pdf/childalgorithm.pdf

12. Thank You

13. Interim Recommendations for the Use of Antiviral Medications for the 2009 � 2010 Influenza SeasonClinician Outreach and Communication ActivityOct 20, 2009 Now lets turn to current antiviral treatment recommendations for influenza Now lets turn to current antiviral treatment recommendations for influenza

14. Pediatric Antiviral Recommendations http://www.cdc.gov/h1n1flu/recommendations_pediatric_supplement.htm

15. Neuraminidase Inhibitors Oseltamivir (Tamiflu) and Zanamivir (Relenza) Randomized clinical trials (RCT): Reduced duration of influenza by 1-1.5 days when administered in 48 hours Pooled RCT analysis: Reduced lower respiratory tract complications, pneumonia, and hospitalization Observational studies*: Oseltamivir reduced mortality among hospitalized adults with lab-confirmed seasonal influenza A virus infections The effectiveness of oseltamivir in treating human influenza A (H1) or (H3) has been studied and the following has been found: Effectiveness in seasonal human influenza: Reduces influenza symptoms by 1 day when administered within 2 days of illness onset May reduce lower respiratory tract complications and hospitalization due to seasonal influenza -Recall that the effectiveness of treatment for H5N1 virus infection is unknown, nonetheless, oseltamivir is currently recommended as first line therapy for H5N1 virus infections -Precautions should be taken when oseltamivir is administered to the following groups of patients: -For people with kidney disease, the dose should be reduced -Oseltamivir is normally not recommended for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown, however, if there is strong suspicion for H5N1 virus infection, the benefits may outweigh the risks -There have been some reports from Japan of self-injury and delirium with the use of oseltamivir in patients with seasonal influenza -The relationship of these reported events to oseltamivir is not known. -Antiviral resistance can develop with treatment, but the frequency of resistance to oseltamivir appears to be low The effectiveness of oseltamivir in treating human influenza A (H1) or (H3) has been studied and the following has been found: Effectiveness in seasonal human influenza: Reduces influenza symptoms by 1 day when administered within 2 days of illness onset May reduce lower respiratory tract complications and hospitalization due to seasonal influenza -Recall that the effectiveness of treatment for H5N1 virus infection is unknown, nonetheless, oseltamivir is currently recommended as first line therapy for H5N1 virus infections -Precautions should be taken when oseltamivir is administered to the following groups of patients: -For people with kidney disease, the dose should be reduced -Oseltamivir is normally not recommended for use during pregnancy or nursing, as the effects on the unborn child or nursing infant are unknown, however, if there is strong suspicion for H5N1 virus infection, the benefits may outweigh the risks -There have been some reports from Japan of self-injury and delirium with the use of oseltamivir in patients with seasonal influenza -The relationship of these reported events to oseltamivir is not known. -Antiviral resistance can develop with treatment, but the frequency of resistance to oseltamivir appears to be low

16. Oseltamivir (Tamiflu) Oral medication: capsule or suspension Capsule may also be compounded into an oral suspension Pediatric dosage depends on age and weight FDA approved in persons aged =1 year Emergency Use Authorization (EUA) approved for use in persons <1 year Side effects include nausea, vomiting Reports of neuropsychiatric events (Japan) Precautions People with kidney disease (reduce dose) Pregnant or nursing women (safety not well studied) Oseltamivir, the most widely available neuraminidase inhibitor drugs is: -Available as a capsule or suspension administered by mouth -Oseltamivir is approved in the U.S. for treatment of human influenza in children aged one year and older -For pediatric patients, the dosage depends on age and weight -For treatment of human influenza A (H1), A (H3), or B virus infection, oseltamivir is administered twice a day, for 5 days -Side effects are generally mild, and may include nausea, vomiting Oseltamivir, the most widely available neuraminidase inhibitor drugs is: -Available as a capsule or suspension administered by mouth -Oseltamivir is approved in the U.S. for treatment of human influenza in children aged one year and older -For pediatric patients, the dosage depends on age and weight -For treatment of human influenza A (H1), A (H3), or B virus infection, oseltamivir is administered twice a day, for 5 days -Side effects are generally mild, and may include nausea, vomiting

17. Zanamivir (Relenza) Orally inhaled powder � via special device FDA approved for: treatment of seasonal influenza (> 7 years) prevention of seasonal influenza (> 5 years) EUA expands treatment indication to hospitalized patients and patients symptomatic for more than 2 days Treatment after 48 hours of symptom onset is still useful in hospitalized patients Side effects: wheezing, breathing problems Precautions Chronic respiratory disease (bronchospasm) Pregnant or nursing women (safety not well studied) Zanamivir is a neuraminidase inhibitor that is not widely available for the treatment of influenza: - It is an orally inhaled powder (shown here) � which is administered by mouth via a special inhaler device - It is approved in the U.S. for treatment of seasonal influenza in patients aged 7 years and older, and for the prevention of seasonal influenza in patients aged 5 years and older - Treatment dosage is one puff in the morning and one at night for 5 days -Side effects may include wheezing and breathing problems Zanamivir is a neuraminidase inhibitor that is not widely available for the treatment of influenza: - It is an orally inhaled powder (shown here) � which is administered by mouth via a special inhaler device - It is approved in the U.S. for treatment of seasonal influenza in patients aged 7 years and older, and for the prevention of seasonal influenza in patients aged 5 years and older - Treatment dosage is one puff in the morning and one at night for 5 days -Side effects may include wheezing and breathing problems

18. Clinical Considerations 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. 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.

19. Treatment Recommendation Early empiric treatment with oseltamivir or zanamivir should be considered for children with suspected or confirmed influenza who have: severe illness; evidence of clinical deterioration regardless of previous health; symptoms of lower respiratory tract involvement; illness requiring hospitalization.

20. Early empiric outpatient treatment for persons at higher risk for complications Children younger than 2 years old Children and adolescents with certain chronic medical or immunosuppressive conditions Pregnant adolescents and adolescents up to 2 weeks postpartum (including following pregnancy loss); Persons younger than 19 years of age who are receiving long-term aspirin therapy

21. Medical Risk Factors 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;

22. Considerations for Children 2 � 4 years old 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. Children aged 2 years to 4 years without high risk conditions (see page 3) and with mild illness do not necessarily require antiviral treatment.

23. Risk Factors for Pediatric Mortality 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�

24. Influenza Diagnosis Treatment, when indicated, should not wait for laboratory test results or confirmation of influenza A negative rapid influenza diagnostic tests (RIDTs) does not rule out influenza The sensitivity of RIDTs in detecting 2009 H1N1 ranges from 10 % to 70% False negative results can also occur with immunofluorescence assays

25. Limited availability of oseltamivir suspension Stocks gone in may states and cities Strategic National Stockpile (SNS) has released suspension to states Release has an extended shelf life based on FDA testing Infants (children less than 1 yr) and children weighing <33 lbs should be considered the highest priority for receiving commercially-prepared suspension

26. Alternatives to commercially-produced suspension For infants (children less than 1 yr) and children weighing <33 lbs, one alternative: Compounded suspension at retail pharmacy For older and heavier children, two alternatives: Compounded suspension at retail pharmacy 30 or 45 mg capsule mixed at home with 5-10 ml of sweet syrup such as applesauce, corn syrup, honey (for children >1 yr), pudding, or chocolate syrup

27. Influenza Diagnosis Treatment, when indicated, should be initiated as early as possible Treatment should not wait for laboratory confirmation of influenza A negative rapid influenza diagnostic tests (RIDTs) does not rule out influenza The sensitivity of RIDTs in detecting 2009 H1N1 has ranged from 10 % to 70%

28. Influenza Vaccination and Treatment In October 2009, monovalent inactivated and live attenuated 2009 H1N1 influenza vaccines became available in the United States.� 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.� Early recognition of illness and treatment when indicated is preferred to chemoprophylaxis for vaccinated children and adolescents after a suspected exposure.

29. Influenza Vaccination and Treatment Live attenuated monovalent 2009 H1N1 influenza vaccine and live attenuated seasonal influenza vaccine should not be administered at the same time. Inactivated monovalent 2009 H1N1 influenza vaccine and inactivated seasonal influenza vaccine can be given at the same time. An inactivated influenza vaccine can be given at the same time as a live attenuated influenza vaccine.

30. Summary of Interim Recommendations for the Use of Antiviral Medications Focus on treating severely ill patients (e.g. hospitalized) and patients with risk factors for severe illness Most treatment is empiric, should be started early, and should not wait for an influenza test result Healthy patients with mild illness don�t usually require treatment Limit use of chemoprophylaxis early treatment of high-risk groups is an alternative, especially among vaccinated children and adolescents