#131: Anti-virals for Flu: Looking for evidence for “Stockpile, store, expire, repeat”
CLINICAL QUESTION
Do neuramidase inhibitors (NIs) oseltamivir (Tamiflu®) and/or zanamivir (Relenza®) improve clinical outcomes in healthy patients with influenza or influenza-like illness?
BOTTOM LINE
Biased, poor quality, mostly unpublished evidence demonstrates that oseltamivir and zanamivir shorten the duration of influenza symptoms by ~1/2 a day. Objectively defined pneumonia or hospitalizations are not decreased.
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EVIDENCE
2014 systematic reviews (three publications) of randomized, placebo-controlled trials (RCTs) including >160,000 pages of previously unreleased clinical study reports.1-3
- Treating influenza-like illness or influenza in primarily healthy adults, oseltamivir (11 RCTs)1,2 and zanamivir (14 RCTs):1,3
- Time to symptom improvement 0.6-0.7 days (~10%) better.1-3
- Zanamivir benefit similar to “relief medications” (like acetaminophen/paracetamol).1,3
- Pneumonia (x-ray confirmed): No benefit.1-3
- Hospitalizations: No benefit1,2 or not reported.1,3
- Adverse events:
- Oseltamivir:1,2
- Number Need to Harm: Nausea=28, vomiting=22.
- Post-marketing surveillance reports (frequency unknown):
- Zanamivir: Bronchospasm.4
- Oseltamivir: Delirium and self-injury.5
- Oseltamivir:1,2
- Time to symptom improvement 0.6-0.7 days (~10%) better.1-3
- Used similar studies1,2 but conclusion based on subgroup of documented influenza.
- Review funded by, and two authors had pre-existing industry financial affiliations, with manufacturer of oseltamivir.
- Five times more likely to report benefits of NI use.
- This includes a systematic review of cohort studies from the 2009-10 pandemic suggesting that NIs decrease mortality in hospitalized patients.8
- Less likely to report on publication bias and quality of included studies.
- Since 1999, oseltamivir sales are >$18 billion, half from governments and company stockpiling. Most have never been used.9
- NIs: Not recommended if symptoms >48 hours.4,5
- Zanamivir: Contraindicated: Asthma or COPD.4
- Oseltamivir: Limited evidence: underlying cardiac or respiratory disease.5
- Limited data suggests NIs likely safe in pregnancy10 although makers of:
- Zanamivir don’t recommend in pregnancy.4
- Oseltamivir conclude insufficient data; only use when potential benefit justifies potential risk to fetus.5
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$ 18 billion – wow