Utilization of Antiviral Medications for Influenza

1. Utilization of Antiviral Medications for Influenza City of Milwaukee Health Department Division of Disease Control and Environmental Health June 27, 2008 Think Health. Act Now! . CITY OF MILWAUKEE HEALTH DEPARTMENT . www.milwaukee.gov/Health Content in this presentation may not be duplicated, copied, or reproduced outside the purview of MHD without permission.

2. Learning Objectives • To increase healthcare provider knowledge and use of antiviral medications for influenza • To facilitate collaboration among healthcare providers to reduce morbidity and mortality via seasonal influenza • To increase awareness of the role of antiviral medications in the event of pandemic influenza

3. Antiviral Medications - Overview • Antiviral medications help decrease the reproduction of influenza viruses • Antiviral medications are 70% to 90% effective in preventing influenza and are useful second line of defense to routine vaccination • Antiviral medications do not interfere with immune response from injected influenza vaccination (inactivated) • Since FluMist is a live-virus vaccine, its efficacy may be reduced or blocked altogether if antivirals are administered less than 48 hours before, or less than 2 weeks after, administration of FluMist

4. Mechanism of Action – Neuraminidase Inhibitors • The viral enzyme Neuraminidase aids in the efficiency of virus progeny released from infected host cells • Neuraminidase inhibitors work by blocking the function of this enzyme. • By preventing release of progeny from infected host cells, neuraminidase inhibitors prevent infection and halt the spread of infection with the respiratory tract. • Neuraminidase inhibitors are effective against all strains of influenza.

5. Mechanism of Action – Adamantanes • Adamantanes appear to disrupt the viral replicative cycle. • Amantadine prevents release of infectious viral nucleic acid into the host cell • Rimantadine inhibits the uncoating of the influenza virus.

6. Benefits of Antiviral Medications • Antiviral medications, when properly administered for influenza: • Reduce the duration of symptoms by one to two days • May reduce the number of clinical cases by reducing the spread of influenza via viral shedding • May reduce hospitalizations and related complications from influenza

7. Types of Antiviral Medications • Neuraminidase Inhibitors: • Oseltamivir (Tamiflu) • Zanamivir (Relenza) • Adamantanes: • Amantadine (Symmetrel) • Rimantadine (Flumandine)

8. Oseltamivir (Tamiflu) • Efficacy: 82% • A neuraminidase inhibitor that possesses activity against both influenza A and B viruses • Approved for ages 1 year and older • Recommended for use during the 2007-2008 influenza season

9. Zanamivir (Relenza) • Efficacy: 84% • A neuraminidase inhibitor that possesses activity against both influenza A and B viruses • Approved for ages 7 years and older (for treatment) or 5 years and older (for prophylaxis) • Not recommended for persons with underlying airways disease (e.g., asthma or chronic obstructive pulmonary diseases) • Recommended for use during the 2007-2008 influenza season

10. Amantadine and Rimantadine • For Influenza A viruses only • Approved for ages 1 year and older • In recent years, a high proportion of influenza A viruses in the U.S. developed resistance to these antiviral medications • Therefore, the CDC recommended against amantadine and rimantadine for treatment or chemoprophylaxis of influenza in the United States during the 2005–2006 influenza season

11. Treatment with Antivirals • Start within 48 hours of onset of influenza-like illness • Use only with a positive diagnosis • Laboratory diagnosis (non-rapid-test) required if influenza not prevalent in the community • Rapid test result or clinical diagnosis sufficient if influenza highly prevalent in community • Duration of treatment: • Neuraminidase inhibitors: 5 days • Adamantanes: 7-10 days (but 2-4 weeks when used with influenza vaccine (killed, injectable) prophylaxis

12. Side Effects • Oseltamivir: nausea, vomiting, diarrhea, bronchitis, abdominal pain, dizziness, headache, cough, insomnia, vertigo, fatigue • Zanamivir: headache, diarrhea, nausea, vomiting, nasal signs and symptoms, bronchitis, cough, sinusitis, ear, nose, and throat infections, dizziness

13. Side Effects-continued • Amantadine: nausea, vomiting, dizziness, and insomnia most common; less common include depression, anxiety, irritability, confusion, anorexia, dry mouth, constipation, ataxia, orthostatic hypotension, headache, somnolence, nervousness, agitation, diarrhea and fatigue • Rimantadine: nausea, vomiting, insomnia, dizziness, headache, anorexia, dry mouth, nervousness, fatigue, abdominal pain, asthenia

14. Prophylactic Use of Antivirals • Can be used to control influenza outbreaks in other closed (e.g., military barracks or college dorm room) or semi-closed settings (e.g., college residential hall) • May encourage development of resistant strains • Antiviral medications must be taken each day for the duration of potential exposure to influenza or 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 status)

15. Pandemic Influenza & Antivirals • Laboratory diagnosis is important to monitor the emergence of antiviral resistance and pandemic influenza • The H5N1 virus is expected to be susceptible to neuraminidase inhibitors such as oseltamivir or zanamivir • Supply of neuraminidase inhibitors is limited for pandemic influenza • The CDC and your state and local health department will provide guidance as to when prophylactic use of antivirals should be considered

16. Pandemic: Priority Groups for Antiviral Prophylaxis • Symptomatic patients admitted to the hospital for influenza • Symptomatic health care workers (HCWs) and EMS providers with direct patient contact • Symptomatic highest risk outpatients (immunocompromised persons, pregnant women) • Symptomatic pandemic health responders, public safety and government decision makers • Symptomatic moderate-risk outpatients (children 12-23 mos., persons ≥65 years old, and persons with underlying health conditions)

17. Pandemic: Priority Groups for Antiviral Prophylaxis 6. Outbreak response in nursing homes and other residential settings 7. HCWs in emergency departments, intensive care units, dialysis centers, and EMS providers 8. Symptomatic pandemic social responders and HCW without direct patient care 9. Symptomatic other outpatients 10. Highest risk asymptomatic outpatients 11. Other HCWs with direct patient contact

18. Special Considerations • Patient’s age • Weight • Renal function • Pre-existing medical conditions • Interaction with other medications • Purpose of prescribing (treatment vs. prophylaxis)

19. References • Centers for Disease Control and Prevention. (2007). Antiviral Agents for Seasonal Influenza: Information for Health Professionals. Retrieved May 20,2008 from http://www.cdc.gov/flu/professionals/antivirals/index.htm • Centers for Disease Control and Prevention. (2006). CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season. Retrieved May 29,2008 from http://www.cdc.gov/flu/han011406.htm • Department of Health and Human Services. (2007). Antiviral Questions. Retrieved May 29,2008 from http://www.pandemicflu.gov/faq/antivirals/ • Centers for Disease Control and Prevention. (2006). Interim Guidance for Influenza Diagnostic Testing During the 2006-2007 Influenza Season. Retrieved June 19, 2008 from http://www.cdc.gov/flu/professionals/diagnosis/0607testingguide.htm • Mascona, Anne. “Neuraminidase Inhibitors for Influenza.” The New England Journal of Medicine 353.13 (2005): 1363-1373. • Physicians Desk Reference. Montvale: Thomson, 2007.

20. City of Milwaukee Health Department Division of Disease Control and Environmental Health 414-286-8034 Think Health. Act Now! . CITY OF MILWAUKEE HEALTH DEPARTMENT . www.milwaukee.gov/Health Content in this presentation may not be duplicated, copied, or reproduced outside the purview of MHD without permission.