utilization of antiviral medications for influenza

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Utilization of Antiviral Utilization of Antiviral Medications for InfluenzaMedications for Influenza

City of Milwaukee Health City of Milwaukee Health Department Department Division of Disease Control Division of Disease Control and Environmental Health and Environmental Health June 27, 2008June 27, 2008



Learning Objectives Learning Objectives

• To increase healthcare provider knowledge and To increase healthcare provider knowledge and use of antiviral medications for influenza use of antiviral medications for influenza

• To facilitate collaboration among healthcare To facilitate collaboration among healthcare providers to reduce morbidity and mortality via providers to reduce morbidity and mortality via seasonal influenza seasonal influenza

• To increase awareness of the role of antiviral To increase awareness of the role of antiviral medications in the event of pandemic influenzamedications in the event of pandemic influenza


Antiviral Medications - OverviewAntiviral Medications - Overview

• Antiviral medications help decrease the reproduction of Antiviral medications help decrease the reproduction of influenza viruses influenza viruses

• Antiviral medications are 70% to 90% effective in Antiviral medications are 70% to 90% effective in preventing influenza and are useful second line of preventing influenza and are useful second line of defense to routine vaccinationdefense to routine vaccination

• Antiviral medications do not interfere with immune Antiviral medications do not interfere with immune response from injected influenza vaccination response from injected influenza vaccination (inactivated) (inactivated)

• Since FluMist is a live-virus vaccine, its efficacy may be Since FluMist is a live-virus vaccine, its efficacy may be reduced or blocked altogether if antivirals are reduced or blocked altogether if antivirals are administered less than 48 hours before, or less than 2 administered less than 48 hours before, or less than 2 weeks after, administration of FluMist weeks after, administration of FluMist


• The viral enzyme Neuraminidase aids in the The viral enzyme Neuraminidase aids in the efficiency of virus progeny released from efficiency of virus progeny released from infected host cells infected host cells

• Neuraminidase inhibitors work by blocking the Neuraminidase inhibitors work by blocking the function of this enzyme. function of this enzyme.

• By preventing release of progeny from infected By preventing release of progeny from infected host cells, neuraminidase inhibitors prevent host cells, neuraminidase inhibitors prevent infection and halt the spread of infection with the infection and halt the spread of infection with the respiratory tract. respiratory tract.

• Neuraminidase inhibitors are effective against all Neuraminidase inhibitors are effective against all strains of influenza. strains of influenza.

Mechanism of Action – Mechanism of Action – Neuraminidase InhibitorsNeuraminidase Inhibitors


• Adamantanes appear to disrupt the viral Adamantanes appear to disrupt the viral replicative cycle. replicative cycle.

• Amantadine prevents release of infectious Amantadine prevents release of infectious viral nucleic acid into the host cellviral nucleic acid into the host cell

• Rimantadine inhibits the uncoating of the Rimantadine inhibits the uncoating of the influenza virus. influenza virus.

Mechanism of Action – Mechanism of Action – AdamantanesAdamantanes


Benefits of Antiviral MedicationsBenefits of Antiviral Medications

• Antiviral medications, when properly Antiviral medications, when properly administered for influenza:administered for influenza:

• Reduce the duration of symptoms by one to two Reduce the duration of symptoms by one to two daysdays

• May reduce the number of clinical cases by May reduce the number of clinical cases by reducing the spread of influenza via viral reducing the spread of influenza via viral sheddingshedding

• May reduce hospitalizations and related May reduce hospitalizations and related complications from influenzacomplications from influenza


Types of Antiviral MedicationsTypes of Antiviral Medications

• Neuraminidase Neuraminidase Inhibitors: Inhibitors:

– Oseltamivir (Tamiflu)Oseltamivir (Tamiflu)

– Zanamivir (Relenza) Zanamivir (Relenza)

• Adamantanes: Adamantanes:

– Amantadine Amantadine (Symmetrel) (Symmetrel)

– Rimantadine Rimantadine (Flumandine)(Flumandine)


Oseltamivir (Tamiflu)Oseltamivir (Tamiflu)

• Efficacy: 82% Efficacy: 82%

• A neuraminidase inhibitor that possesses A neuraminidase inhibitor that possesses activity against both influenza A and B activity against both influenza A and B virusesviruses

• Approved for ages 1 year and older Approved for ages 1 year and older

• Recommended for use during the 2007-Recommended for use during the 2007-2008 influenza season2008 influenza season


Zanamivir (Relenza)Zanamivir (Relenza)

• Efficacy: 84%Efficacy: 84%

• A neuraminidase inhibitor that possesses activity A neuraminidase inhibitor that possesses activity against both influenza A and B virusesagainst both influenza A and B viruses

• Approved for ages 7 years and older (for Approved for ages 7 years and older (for treatment) or 5 years and older (for prophylaxis)treatment) or 5 years and older (for prophylaxis)

• Not recommended for persons with underlying Not recommended for persons with underlying airways disease (e.g., asthma or chronic airways disease (e.g., asthma or chronic obstructive pulmonary diseases)obstructive pulmonary diseases)

• Recommended for use during the 2007-2008 Recommended for use during the 2007-2008 influenza seasoninfluenza season


Amantadine and Rimantadine Amantadine and Rimantadine

• For Influenza A viruses onlyFor Influenza A viruses only

• Approved for ages 1 year and olderApproved for ages 1 year and older

• In recent years, a high proportion of influenza A In recent years, a high proportion of influenza A viruses in the U.S. developed resistance to viruses in the U.S. developed resistance to these antiviral medicationsthese antiviral medications

• Therefore, the CDC recommended against Therefore, the CDC recommended against amantadine and rimantadine for treatment or amantadine and rimantadine for treatment or chemoprophylaxis of influenza in the United chemoprophylaxis of influenza in the United States during the 2005–2006 influenza season States during the 2005–2006 influenza season


Treatment with Antivirals Treatment with Antivirals

• Start within 48 hours of onset of influenza-like illnessStart within 48 hours of onset of influenza-like illness

• Use only with a positive diagnosisUse only with a positive diagnosis

– Laboratory diagnosis (non-rapid-test) required if influenza not Laboratory diagnosis (non-rapid-test) required if influenza not prevalent in the communityprevalent in the community

– Rapid test result or clinical diagnosis sufficient if influenza highly Rapid test result or clinical diagnosis sufficient if influenza highly prevalent in communityprevalent in community

• Duration of treatment:Duration of treatment:

– Neuraminidase inhibitors: 5 daysNeuraminidase inhibitors: 5 days

– Adamantanes: 7-10 days (but 2-4 weeks when used with Adamantanes: 7-10 days (but 2-4 weeks when used with influenza vaccine (killed, injectable) prophylaxisinfluenza vaccine (killed, injectable) prophylaxis


Side EffectsSide Effects

• Oseltamivir: nausea, Oseltamivir: nausea, vomiting, diarrhea, vomiting, diarrhea, bronchitis, abdominal bronchitis, abdominal pain, dizziness, pain, dizziness, headache, cough, headache, cough, insomnia, vertigo, fatigue insomnia, vertigo, fatigue

• Zanamivir: headache, Zanamivir: headache, diarrhea, nausea, diarrhea, nausea, vomiting, nasal signs and vomiting, nasal signs and symptoms, bronchitis, symptoms, bronchitis, cough, sinusitis, ear, cough, sinusitis, ear, nose, and throat nose, and throat infections, dizzinessinfections, dizziness


Side Effects-continuedSide Effects-continued

• Amantadine: nausea, vomiting, dizziness, and Amantadine: nausea, vomiting, dizziness, and insomniainsomnia most common; less common include most common; less common include depressiondepression, , anxietyanxiety, irritability, confusion, , irritability, confusion, anorexiaanorexia, , dry mouthdry mouth, constipation, ataxia, , constipation, ataxia, orthostatic hypotension, headache, somnolence, orthostatic hypotension, headache, somnolence, nervousness, agitation, diarrhea and fatiguenervousness, agitation, diarrhea and fatigue

• Rimantadine: nausea, vomiting, insomnia, Rimantadine: nausea, vomiting, insomnia, dizziness, headache, anorexia, dry mouth, dizziness, headache, anorexia, dry mouth, nervousness, fatigue, abdominal pain, asthenianervousness, fatigue, abdominal pain, asthenia


Prophylactic Use of AntiviralsProphylactic Use of Antivirals

• Can be used to control influenza outbreaks in other Can be used to control influenza outbreaks in other closed (e.g., military barracks or college dorm room) or closed (e.g., military barracks or college dorm room) or semi-closed settings (e.g., college residential hall) semi-closed settings (e.g., college residential hall)

• May encourage development of resistant strainsMay encourage development of resistant strains

• Antiviral medications must be taken each day for the Antiviral medications must be taken each day for the duration of potential exposure to influenza or until duration of potential exposure to influenza or until immunity after vaccination develops immunity after vaccination develops

• Antibody development after vaccination takes about two Antibody development after vaccination takes about two weeks in adults and can take longer in children weeks in adults and can take longer in children depending on age and vaccination status) depending on age and vaccination status)


Pandemic Influenza & AntiviralsPandemic Influenza & Antivirals

• Laboratory diagnosis is important to monitor the Laboratory diagnosis is important to monitor the emergence of antiviral resistance and pandemic emergence of antiviral resistance and pandemic influenzainfluenza

• The H5N1 virus is expected to be susceptible to The H5N1 virus is expected to be susceptible to neuraminidase inhibitors such as oseltamivir or neuraminidase inhibitors such as oseltamivir or zanamivir zanamivir

• Supply of neuraminidase inhibitors is limited for Supply of neuraminidase inhibitors is limited for pandemic influenzapandemic influenza

• The CDC and your state and local health department will The CDC and your state and local health department will provide guidance as to when prophylactic use of provide guidance as to when prophylactic use of antivirals should be considered antivirals should be considered


Pandemic: Priority Groups Pandemic: Priority Groups for Antiviral Prophylaxis for Antiviral Prophylaxis

1.1. Symptomatic patients admitted to the hospital for Symptomatic patients admitted to the hospital for influenzainfluenza

2.2. Symptomatic health care workers (HCWs) and EMS Symptomatic health care workers (HCWs) and EMS providers with direct patient contactproviders with direct patient contact

3.3. Symptomatic highest risk outpatients Symptomatic highest risk outpatients (immunocompromised persons, pregnant women)(immunocompromised persons, pregnant women)

4.4. Symptomatic pandemic health responders, public Symptomatic pandemic health responders, public safety and government decision makerssafety and government decision makers

5.5. Symptomatic moderate-risk outpatients (children 12-23 Symptomatic moderate-risk outpatients (children 12-23 mos., persons ≥65 years old, and persons with mos., persons ≥65 years old, and persons with underlying health conditions)underlying health conditions)


Pandemic: Priority Groups Pandemic: Priority Groups for Antiviral Prophylaxisfor Antiviral Prophylaxis

6. Outbreak response in nursing homes and other 6. Outbreak response in nursing homes and other residential settingsresidential settings

7. HCWs in emergency departments, intensive 7. HCWs in emergency departments, intensive care units, dialysis centers, and EMS providerscare units, dialysis centers, and EMS providers

8. Symptomatic pandemic social responders and 8. Symptomatic pandemic social responders and HCW without direct patient careHCW without direct patient care

9. Symptomatic other outpatients9. Symptomatic other outpatients

10. Highest risk asymptomatic outpatients10. Highest risk asymptomatic outpatients

11. Other HCWs with direct patient contact11. Other HCWs with direct patient contact


Special ConsiderationsSpecial Considerations

• Patient’s agePatient’s age

• Weight Weight

• Renal functionRenal function

• Pre-existing medical conditionsPre-existing medical conditions

• Interaction with other medicationsInteraction with other medications

• Purpose of prescribing (treatment vs. Purpose of prescribing (treatment vs. prophylaxis)prophylaxis)


References References

• Centers for Disease Control and Prevention. (2007). Centers for Disease Control and Prevention. (2007). Antiviral Agents for Antiviral Agents for Seasonal Influenza: Information for Health Professionals. Seasonal Influenza: Information for Health Professionals. Retrieved May Retrieved May 20,2008 from 20,2008 from http://www.cdc.gov/flu/professionals/antivirals/index.htmhttp://www.cdc.gov/flu/professionals/antivirals/index.htm

• Centers for Disease Control and Prevention. (2006). Centers for Disease Control and Prevention. (2006). CDC Recommends CDC Recommends against the Use of Amantadine and Rimantadine for the Treatment or against the Use of Amantadine and Rimantadine for the Treatment or Prophylaxis of Influenza in the United States during the 2005–06 Influenza Prophylaxis of Influenza in the United States during the 2005–06 Influenza Season. Season. Retrieved May 29,2008 from Retrieved May 29,2008 from http://www.cdc.gov/flu/han011406.htmhttp://www.cdc.gov/flu/han011406.htm

• Department of Health and Human Services. (2007). Department of Health and Human Services. (2007). Antiviral Questions.Antiviral Questions. Retrieved May 29,2008 from Retrieved May 29,2008 from http://www.pandemicflu.gov/faq/antivirals/http://www.pandemicflu.gov/faq/antivirals/

• Centers for Disease Control and Prevention. (2006). Centers for Disease Control and Prevention. (2006). Interim Guidance for Interim Guidance for Influenza Diagnostic Testing During the 2006-2007 Influenza Season. Influenza Diagnostic Testing During the 2006-2007 Influenza Season. Retrieved June 19, 2008 from Retrieved June 19, 2008 from http://www.cdc.gov/flu/professionals/diagnosis/0607testingguide.htmhttp://www.cdc.gov/flu/professionals/diagnosis/0607testingguide.htm

• Mascona, Anne. “Neuraminidase Inhibitors for Influenza.” The Mascona, Anne. “Neuraminidase Inhibitors for Influenza.” The New New England Journal of Medicine 353.13 (2005): 1363-1373.England Journal of Medicine 353.13 (2005): 1363-1373.

• Physicians Desk Reference. Montvale: Thomson, 2007.Physicians Desk Reference. Montvale: Thomson, 2007.


City of Milwaukee Health Department City of Milwaukee Health Department Division of Disease Control and Division of Disease Control and Environmental Health Environmental Health 414-286-8034414-286-8034


utilization of antiviral medications for influenza

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