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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.
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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