Stockpile, use during outbreaks, restock, repeat

Clinical question

How effective are oseltamivir and zanamivir for decreasing postexposure transmission of influenza?

Bottom line

For institutionalized seniors, 6 weeks of oseltamivir or 14 days of zanamivir will prevent 1 additional influenza case in every 25 to 27 patients treated. For every 7 to 8 households given postexposure prophylaxis (PEP), 1 household will avoid anyone developing influenza.

Evidence

Best evidence is from mostly unpublished, industry sponsored RCTs¹ (1990s) and 2 systematic reviews.^2,3 Results are based on laboratory-confirmed, symptomatic influenza.

• Institutionalized seniors.

  • -Two RCTs examined zanamivir PEP during an influenza outbreak (10 cases or 10% with influenza) using 14 days of zanamivir (10 mg/d) versus rimantadine (N = 385, 98% vaccinated) or placebo (N = 489, 9% vaccinated).

    • —At 15 days 2.9% of those taking zanamivir had influenza versus 7.4% of those taking rimantadine (statistically significant); 6.3% of those taking zanamivir had influenza versus 9.2% for placebo (not significant).

    • —Pooled (by authors): 4.6% versus 8.3%; NNT = 27.

  • -A study of 6 weeks of oseltamivir (75 mg/d) or placebo in 548 (69% vaccinated) patients when influenza was “noted in the community” found influenza at 8 weeks in 0.3% of patients versus 4.4% for placebo; NNT = 25.

• For households, 3 clustered (by household) RCTs examined PEP when a household member was diagnosed with influenza-like illness (mean age of contacts 24 to 33 years; < 15% vaccinated; children excluded).

  • -Zanamivir or placebo for 10 days: 4.6% of households had 1 or more new influenza cases at 11 days (pooled)^1,4 versus 20.5% for placebo; NNT = 7.

  • -Oseltamivir (75 mg/d) or placebo for 7 days: 2.1% of households had 1 or more new influenza cases at 21 days^1,5 versus 14.6% for placebo; NNT = 8.

• There was no difference in hospitalizations.^2,3 Multiple analyses were performed for adverse effects.³ For oseltamivir: psychiatric events (NNH = 95), headache (NNH= 32), and nausea (NNH = 25).^2,3 For zanamivir: no difference in treatment trials.³ Limitations include inconsistent outcome definitions and selective reporting.²

Context

• Canada stockpiles about 60 million doses (primarily oseltamivir); about 50% expire before use.⁶

• In closed facility outbreaks, guidelines recommend treating the index case, vaccinating the unvaccinated,⁷ and PEP for the longer of 14 days or 7 days after the onset of symptoms in the last infected person.⁸ For households, PEP is recommended only if vaccination is contraindicated.⁷

Implementation

Antiviral PEP is not a substitute for influenza vaccination.⁸ Vaccine efficacy is determined by seasonal prevalence and vaccine matching. For every 13 long-term care residents vaccinated, 1 fewer will develop influenza.⁹ Evidence suggests vaccination of health care workers decreases long-term care residents’ mortality.^10,11 While 72% of FPs reported being vaccinated, overall health care worker vaccination rates are about 50%.¹² Institution outbreaks should be considered when 2 or more residents have influenza-like symptoms within 72 hours of one another.⁸