Influenza chemoprophylaxis

Foroud Shahbazi, Pharm.D

Outline

1. Post-exposure Chemoprophylaxis Effectiveness

2. Pre-exposure Chemoprophylaxis

• Duration of Chemoprophylaxis

• Considerations for Antiviral Use When Antiviral Supplies Are Limited

• Control of Influenza Outbreaks in Institutions

• Dosing

Introduction

• Influenza is always serious – each year in the United States, seasonal

influenza results, on average, in an estimated 36,000 deaths and more

than 200,000 hospitalizations from flu-related causes.

Spread

• Primarily through respiratory droplets

• Coughing

• Sneezing

• Touching respiratory droplets on

yourself, another person, or an object,

then touching mucus membranes

(e.g., mouth, nose, eyes) without

washing hands

Signs and Symptoms

Natural history Flu vaccination prevention• Healthy individuals usually self limited

• Vaccination efficacy: 70-90%

• Influenza vaccination is the best prevention method and first choice Even

vaccination is not 100% efficacious.

• Efficacy reaches only 40% in the elderly

• Influenza related complications, such as pneumonia, hospitalization and influenza

specific and overall mortality

1. Cochrane Database of Systematic Reviews: CD0012692. PLoS One. 2013;8(4):e60348

High risk groups (Response, Complications)

• Cardiac or pulmonary disorders

• DM and other metabolic diseases

• Active cancer, Immunosuppressive agents, HIV (CD4 < 200 cells/microL)

• Renal and hepatic disease

• Hemoglobinopathy

• Neurologic conditions (seizure, cognitive dysfunction, NM)

• Children <2 years, Adults ≥65 years of age

• Nursing home residents

• Long term aspirin users (<19 y/o)

• Morbid obese (BMI] ≥40)

Chemoprophylaxis

• Lower response tare

• Higher complications

•Post-exposure•Pre-exposure

Currently available agents

• ADAMANTANES )M2 proton channel inhibitors (amantadine and rimantadine) //( Resistance / Adverse effects)

• Neuraminidase inhibitors

Clin Microbiol Infect 2015; 21: 222–225

Definition of Close Contacts

A. As persons within approximately 6 feet (2 meters) or within the room or care area of a

confirmed or probable novel influenza A case patient for a prolonged period of time

or

B. Direct contact with infectious secretions while the case patient was likely to be infectious

(beginning 1 day prior to illness onset and continuing until resolution of illness)

1. MMWR Morbidity and mortality weekly report 2006; 55 Suppl 1: 3-62. Emerging infectious diseases 2008; 14(11): 1819-21.

Post exposure chemoprophylaxis

• Has been effective in the prevention of influenza illness among persons administered

chemoprophylaxis after a household member or other close contact had laboratory-

confirmed influenza (zanamivir: 72%–82%; oseltamivir: 68%–89%)

• In pediatric: oseltamivir was started within 24 hours of illness onset, the median time to

illness resolution was shortened by 3.5 days compared with placebo

Advisory Committee on Immunization Practices [ACIP], 2010. MMWR 2010;59[No. RR-8])

Efficacy

• Effective in:

• Healthy individuals

• At Higher risk of flu complications

• Nursing home residents

• BMT, MM, HIV

• Prophylaxis should be individualized

Recommendations PEP

1. During influenza outbreaks in long-term care facilities in elderly and chronically ill

residents regardless of prior influenza vaccination

2. Unvaccinated individuals with close contact

3. Vaccinated Individuals at high risk of influenza complication /poor match between

the vaccine and circulating viruses

4. Poor vaccine responders (rituximab, transplantation,

5. Pregnancy

6. Other groups should be individualized

• Should be started within 48 hours

Novel influenza risk stratification

• Highest-risk exposure groups: Household or close family member

contacts of a confirmed or probable case

• Moderate-risk exposure groups: Health care personnel with

unprotected close contact with a confirmed or probable case

• Low-risk exposure groups : Others who have had social contact of a

short duration with a confirmed or probable case in a non-hospital

setting (e.g., in a community or workplace environment)

http://www.cdc.gov/flu/avianflu/novel-av-chemoprophylaxis-guidance.htm

Chemoprophylaxis

1. In highest-risk exposure groups, chemoprophylaxis should be

administered.

2. In moderate-risk exposure groups, chemoprophylaxis could be considered.

3. In low-risk exposure groups, chemoprophylaxis is not routinely

recommended.

Duration of prophylaxis

• Recommended duration is

• Ten days when administered after a household exposure

• Seven days after the most recent known exposure in other situations.

• For control of outbreaks in long term care facilities and hospitals

• for a minimum of 2 weeks and up to 1 week after the most recent known

case was identified

Dosing

Preexposure Chemoprophylaxis

• Similar efficacy were noted with both agents in preventing febrile,

laboratory-confirmed influenza illness (zanamivir: 84%; oseltamivir:

82%)

• Similar results were seen in nursing home residents

• Effective in immunocompromised patients

1. Transplant Infectious Disease 2013: 0: 1–142. MMWR 2010;59[No. RR-8])3. Clinical Infectious Diseases 2009; 48:1003–32

High risk

• Residents of nursing homes and chronic care facilities

• Adults ≥65 years of age

• Pregnant women and women up to two weeks postpartum

• Individuals who are morbidly obese (body mass index of 40 kg/m2 and higher )

• Individuals with chronic medical conditions

Recommendation pre-exposure

• Who are unable to mount an immune response to the vaccine, may be given throughout the

period of peak influenza activity (usuall6 to8 weeks) (1)

• Considered for high-risk persons with frequent exposures (health care workers, public

health workers, or first responders) to 2009 H1N1 after consultation with local public health

authorities (2)

1. MMWR 2010;59[No. RR-8]2. Mayo Clin Proc. 2010;85:64-76

Ann Pharmacother 2012;46:255-64.

Number of Oseltamivir 75 mg Capsules and Amount of Vehicle (cherry syrup, simple syrup, or Ora-Sweet(R) SF) Needed to Prepare the Total

Volume of a Compounded Oral Suspension (6 mg/mL)

Total Volume Needed 75 mL 100 mL 125 mL 150 mL

Number of 75 mg Capsules Required

6 caps (450 mg)

8 caps (600 mg)

10 caps (750 mg)

12 caps (900 mg)

Amount of Water 5 mL 7 mL 8 mL 10 mL

Required Volume of Vehicle (cherry syrup, simple syrup, or

Ora-Sweet(R) SF) 69 mL 91 mL 115 mL 137 mL

KEY: mg = milligrams; mL = milliliters; caps = capsules

Special Population

• Pregnant Women

• Persons with Impaired Renal Function

• Persons with Liver Disease

• Persons with Seizure Disorders

• Persons with Immunosuppression

Adverse effects

Education

• Chemoprophylaxis lowers but does not eliminate the risk for

influenza, that susceptibility to influenza returns once the antiviral

medication is stopped, and that influenza vaccination is recommended

if available

• Seek medical evaluation as soon as they develop a febrile respiratory

illness

Conclusion

• Preexposure prophylaxis has a very limited role because of concerns about

the supply of antivirals, need for long-term use, and the potential for

adverse effects and promotion of antiviral resistance .

• Preexposure prophylaxis should be used only in individuals at very high

risk for influenza complications (e.g. severely immunocompromised hosts)

who cannot be protected by other means and have a high risk of exposure