1. Influenza chemoprophylaxis Foroud Shahbazi, Pharm.D

2. 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

3. 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.

6. 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

7. Signs and Symptoms

8. 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: CD001269 2.PLoS One. 2013;8(4):e60348

9. 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)

10. Chemoprophylaxis Lower response tare Lower response tare Higher complications Higher complications

11. Currently available agents ADAMANTANES )M2 proton channel inhibitors (amantadine and rimantadine) //( Resistance / Adverse effects) Neuraminidase inhibitors Clin Microbiol Infect 2015; 21: 222–225

12. 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: 3-6 2.Emerging infectious diseases 2008; 14(11): 1819-21.

13. 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])

14. Efficacy Effective in: Healthy individuals At Higher risk of flu complications Nursing home residents BMT, MM, HIV Prophylaxis should be individualized

15. 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

16. 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

17. 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.

18. 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

19. Dosing

20. 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: 1–14 2.MMWR 2010;59[No. RR-8]) 3.Clinical Infectious Diseases 2009; 48:1003–32

21. 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/m 2 and higher ) Individuals with chronic medical conditions

22. 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

23. Ann Pharmacother 2012;46:255-64.

27. Special Population Pregnant Women Persons with Impaired Renal Function Persons with Liver Disease Persons with Seizure Disorders Persons with Immunosuppression

28. Adverse effects

29. 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

30. 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