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#176 Stockpile, use during outbreaks, re-stock and repeat


CLINICAL QUESTION
QUESTION CLINIQUE
How effective are oseltamivir and zanamivir at decreasing post-exposure transmission of influenza?


BOTTOM LINE
RÉSULTAT FINAL
For institutionalized seniors, six weeks of oseltamivir or 14 days of zanamivir or will prevent one additional influenza case in every 25-27 treated. For every 7-8 householdgiven post-exposure prophylaxis (PEP)one household will avoid anyone developing influenza.  



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EVIDENCE
DONNÉES PROBANTES
Mostly unpublished, industry-sponsored, Randomized Controlled Trials (RCTs)1 (from 1990s) and two systematic reviews.2,3 Results all lab confirmed, symptomatic influenza. 
  • Institutionalized seniors: 
    • ZanamivirPEP during influenza outbreak (ten cases or 10% with influenza): 
      • Two RCTs of 14 days of zanamivir 10 mg/day versus rimantadine (was standard of care) or placebo in 385 (98% vaccinated) and 489 (9% vaccinated) residents, respectively. 
        • Influenza at 15 days:  
          • 2.9% versus 7.4% (rimantidine); statistically significant. 
          • 6.3% versus 9.2% (placebo); not statistically different. 
            • Pooled (by authors): 4.6% versus 8.3%, Number Needed to Treat (NNT)=27.  
    • Oseltamivir: Six weeks of oseltamivir 75 mg/day or placebo in 548 (69% vaccinated) patients when influenza “noted in the community.”  
      • Influenza at eight weeks0.3% versus 4.4% (placebo), NNT=25. 
  • Households 
    • Three clustered (by household) placebo-controlled RCTs when household member diagnosed with influenza-like illnessContacts mean ages 24-33 years (children excluded)<15% vaccinated:   
      • Zanamivir: Ten days of zanamivir or placebo; households with ≥1 new influenza case at 11 days (pooled): 1,4 
        • 4.6% versus 20.5% (placebo), NNT=7. 
      • Oseltamivir: Seven days of oseltamivir 75 mg/day or placebo; households with ≥1 new influenza case at 21 days: 1,5    
        • 2.1% versu14.6% (placebo), NNT=8. 
  • Other outcomes:  
    • Hospitalizations: No difference.2,3  
    • Adverse effects: Multiple analyses performed.3 
      • Oseltamivir: Psychiatric events Number Needed to Harm (NNH)=95; headache NNH=32; nausea NNH=25.2,3 
      • Zanamivir: No difference in treatment trials3 
  • Limitations: Inconsistent outcome definitionsselective reporting.2 
CONTEXT:  
  • Canada stockpiles ~60 million doses of primarily oseltamivir, ~50% expire before use.6 
  • Guidelines recommend:  
    • Closed facility outbreaks:  
      • Treating index case and vaccinating the unvaccinated7  
      • PEP for 14 days or seven days after the onset of symptoms in the last infected person, whichever is longer.8 
    • Household contact: PEP only if vaccination contra-indicated.7 


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Author(s)
Auteur(s)
  • Michael R Kolber BSc MD CCFP MSc
  • Christina Korownyk MD CCFP

1. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Available at: http://dx.doi.org/10.5061/dryad.77471. Last Accessed: October 14, 2016. RCTs referenced: NAIA3003, NAIA3004, WV15825. NAI30031, NAI30010, WV15799.

2. Jefferson T, Jones MA, Doshi P, et al. Cochrane Database Syst Rev. 2014; 4:CD008965.

3. Heneghan CJ, Onakpoya I, Jones MA, et al. Health Technol Assess. 2016; 20(42):1-242.

4. Hayden FG, Gubareva LV, Monto AS, et al. N Engl J Med. 2000; 343:1282-9.

5. Welliver R, Monto AS, Carewicz O, et al. JAMA. 2001; 285:748-54.

6. Public Health Agency of Canada. Available at: http://www.phac-aspc.gc.ca/cpip-pclcpi/assets/pdf/annex_e-eng.pdf. Last Accessed: October 20, 2016.

7. Aoki FY, Allen UD, Stiver HG, et al. Can J Infect Dis Med Microbiol. 2013; 24:Suppl C:1C-15C.

8. Harper SA, Bradley JS, Englund JA, et al. Clin Infect Dis. 2009; 48:1003-32.

Authors have no conflicts of interest to declare. We wish to thank Dr. T. Jefferson for advising us of the location of the unpublished reports.