#176 Stockpile, use during outbreaks, re-stock and repeat
CLINICAL QUESTION
How effective are oseltamivir and zanamivir at decreasing post-exposure transmission of influenza?
BOTTOM LINE
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 households given post-exposure prophylaxis (PEP), one household will avoid anyone developing influenza.
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EVIDENCE
Mostly unpublished, industry-sponsored, Randomized Controlled Trials (RCTs)1 (from 1990s) and two systematic reviews.2,3 Results all lab confirmed, symptomatic influenza.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:
- Zanamivir: PEP 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.
- Influenza at 15 days:
- 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.
- Oseltamivir: Six weeks of oseltamivir 75 mg/day or placebo in 548 (69% vaccinated) patients when influenza “noted in the community.”
- Influenza at eight weeks: 0.3% versus 4.4% (placebo), NNT=25.
- Zanamivir: PEP during influenza outbreak (ten cases or 10% with influenza):
- Households:
- Three clustered (by household) placebo-controlled RCTs when household member diagnosed with influenza-like illness. Contacts’ 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% versus 14.6% (placebo), NNT=8.
- Zanamivir: Ten days of zanamivir or placebo; households with ≥1 new influenza case at 11 days (pooled): 1,4
- Three clustered (by household) placebo-controlled RCTs when household member diagnosed with influenza-like illness. Contacts’ mean ages 24-33 years (children excluded), <15% vaccinated:
- 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 definitions, selective reporting.2
- 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
- Closed facility outbreaks:
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