# Presentation: 110138

## Antiviral Medications for Influenza

- Tim Uyeki MD, MPH
- Influenza Branch
- Division of Viral and Rickettsial Diseases
- National Center for Infectious Diseases

## Antiviral medications

- 2 Classes of Medications Available
- Adamantanes
- Amantadine, Rimantadine
- Activity only against influenza A viruses
- Neuraminidase inhibitors
- Oseltamivir, Zanamivir
- Activity against influenza A and influenza B viruses

## Antiviral treatment

- 4 approved prescription drugs
- Different approved age groups
- Amantadine: ≥1 year; Rimantadine: adults
- Oseltamivir:  ≥1 year; Zanamivir: ≥7 years
- Dosage varies by age and weight
- Early treatment of influenza
- Begin within 48 hours of illness onset
- Duration:  5 days

## Antiviral treatment

- All 4 antiviral medications are equally efficacious when used for early treatment
- Decrease the duration and symptoms of uncomplicated influenza by approximately 1 day
- Decrease viral shedding
- Early treatment with neuraminidase inhibitors can reduce some complications
- Otitis media, lower respiratory tract complications, antibiotic use, hospitalizations

*continued*

## Antiviral chemoprophylaxis

- 3 approved prescription drugs
- Different approved age groups
- Amantadine, Rimantadine: ≥1 year
- Oseltamivir: ≥13 years
- Dosage varies by age and weight
- Approximately 70-90% effective in preventing influenza illness
- Does not interfere with immune response to inactivated influenza vaccine

## Amantadine, Rimantadine

- Chemically related, tablet and syrup
- Mechanism of action
- Interfere with M2 ion channel of influenza A viruses
- Interfere with virus assembly during replication of influenza A viruses
- Decrease the release of influenza A viral particles into the host cell
- Decrease influenza A viral shedding
- No activity against influenza B viruses

## Amantadine adverse effects

- Primarily excreted unchanged in urine
- Adverse effects
- Gastrointestinal:  nausea, vomiting
- Central nervous system:  difficulty concentrating, nervousness, insomnia, exacerbation of seizures
- Dosage reduction
- Kidney disease; Persons 65 years
- Any adverse effects (convulsions)
- Avoid in persons with psychiatric disorders

## Rimantadine adverse effects

- Metabolized in the liver
- Adverse effects
- Gastrointestinal:  nausea, vomiting
- Central nervous system: less than amantadine
- Dosage reduction
- Kidney disease, Liver disease
- Persons 65 years
- Any adverse effects
- Avoid in persons with psychiatric disorders

## Amantadine, RimantadineAntiviral Resistance:

- Rapid development of resistance in 10-30% of treated (can develop in 2-5 days)
- Resistant viruses
- Cross-resistance
- Not more easily transmitted or cause more serious illness than non resistant strains
- Transmission in households, institutions
- No evidence of community circulation
- Susceptible to neuraminidase inhibitors

## Oseltamivir, Zanamivir 

- Chemically related
- Different routes of administration
- Oseltamivir: tablet, suspension
- Zanamivir:   orally inhaled powder
- Mechanism of action:
- Block active site of neuraminidase
- Reduce the amount of viral particles released from infected cells
- Decrease shedding of influenza A and influenza B viruses

## Oseltamivir adverse effects

- Metabolized by liver, excreted in urine
- Adverse effects
- Gastrointestinal (nausea, vomiting)
- Dosage reduction:
- Kidney disease

## Zanamivir adverse effects

- Not metabolized, excreted unchanged
- Adverse effects
- Gastrointestinal (nausea, diarrhea)
- Headache
- Cough (bronchospasm in persons with pulmonary disease: not recommended for persons with underlying pulmonary disease)

## Neuraminidase Inhibitor Resistance

- Cross-resistance
- Frequency
- 5.5% in oseltamivir pediatric treatment study (U.S.)
- 18% in oseltamivir pediatric treatment study (Japan)
- Global Neuraminidase Inhibitor Susceptibility Network

## CDC interim recommendations*

- These interim recommendations are provided, in conjunction with previously issued recommendations on use of vaccine, to reduce the impact of influenza on persons at high risk for developing severe complications secondary to infection (including PLWHA).
- The recommendations are not intended to guide the use of these medications in other situations, such as outbreaks of avian influenza.

- *Posted Oct. 19, 2004

## CDC interim recommendations* 

***CDC encourages:***
- “the use of amantadine or rimantadine for chemoprophylaxis and use of oseltamivir or zanamivir for treatment as supplies allow, in part to minimize the development of adamantane resistance among circulating influenza viruses.”

*continued*

- *Posted Oct. 19, 2004

## CDC interim recommendations*

***Priority groups for treatment:***
- Any person experiencing a potentially life-threatening influenza-related illness
- Any person at high risk for serious complications of influenza (including PLWHA) and who is within the first 2 days of illness onset

- *Posted Oct. 19, 2004

*continued*

## CDC interim recommendations*

***Priority Groups for Chemoprophylaxis:***
- Outbreaks in institutions caring for high risk persons (including PLWHA) -- for patients, residents and unvaccinated staff (e.g. nursing homes, hospitals)
- Continue for 1 week following end of outbreak
- Includes vaccinated, unvaccinated residents
- Recently vaccinated persons (post-vaccination)
- Implementation of additional control measures
- High risk persons likely to be exposed to persons with influenza (e.g., family/household setting)

- *Posted Oct. 19, 2004

*continued*

## CDC interim recommendations*

***Antivirals can be considered:***
- Chemoprophylaxis of persons in communities where influenza viruses are circulating
- High risk persons unable to be vaccinated
- Vaccinated high risk persons in post-vaccination period while awaiting full immune response
- Immunosuppressed persons (e.g. PLWHA) who might not mount adequate immune response to vaccine
- Health care workers with direct patient care responsibilities unable to obtain vaccine
- Treatment of persons without high risk conditions

- *Posted Oct. 19, 2004

*continued*

## CDC interim recommendations*

***Antivirals are not recommended:***
- Where the supplies of both influenza vaccine and influenza antiviral medications may not be sufficient to meet demand, CDC does not recommend the use of influenza antiviral medications for chemoprophylaxis of non-high risk persons in the community.

- *Posted Oct. 19, 2004

*continued*

## CDC interim recommendations*

***Strategic National Stockpile ***
- Resource when unavailable through private sector sources
- Rimantadine tablets and syrup
- May be available for use in outbreak settings
- May be requested only by State/Territory Health Departments -- urgent priority need, unable to procure meds from private distributors

- *Posted Oct. 19, 2004

*continued*

## Antiviral supply

- CDC and FDA are monitoring supplies of antiviral medications
- Antiviral supplies are estimated to be adequate at the current time