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Cochrane reviewers have been skeptical about the efficacy of the neuraminidase inhibitors zanamivir (Relenza) and oseltamivir (Tamiflu) for treating patients with influenza (NEJM JW Gen Med Jan 5 2010). However, because much of the proprietary data on these drugs have been unavailable for public review, their conclusions have been tentative. Now, two new Cochrane reviews incorporate thousands of pages of previously unavailable data from the drugs' manufacturers.
In a review of 20 randomized, controlled studies of oseltamivir, investigators concluded that the drug reduced mean duration of influenza symptoms in adults by about 17 hours (from 7 days to 6.3 days) and in otherwise healthy children by about 29 hours; the drug had no significant effect on duration of symptoms in children with asthma. Oseltamivir slightly lowered rates of unverified pneumonia among adults (but not among children) but had no effect on hospital admission rates among either adults or children. Because virtually no influenza-related deaths occurred among study participants, the drug's effect on mortality could not be addressed. In prophylaxis studies, the drug lowered the incidence of symptomatic influenza by 55% during 42 days of follow-up. Adverse effects included nausea and vomiting.
In a review of 26 studies of the inhaled medication zanamivir, researchers concluded that the drug reduced mean duration of symptoms by about 14 hours in adults (from 6.6 days to 6 days) and had no significant effect on duration of symptoms in children. Zanamivir did not prevent pneumonia, otitis media, or sinusitis among either adults or children. The studies did not report hospital admission rates. In prophylaxis studies, zanamivir lowered risk for symptomatic influenza in adults and children by about 60% during roughly 1 month of follow-up. No adverse effects were associated with the drug.
Jefferson T et al. Oseltamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ 2014 Apr 9; 348:g2545. (http://dx.doi.org/10.1136/bmj.g2545)
Heneghan CJ et al. Zanamivir for influenza in adults and children: Systematic review of clinical study reports and summary of regulatory comments. BMJ 2014 Apr 9; 348:g2547. (http://dx.doi.org/10.1136/bmj.g2547)
Comment
These two long, meticulously documented analyses deliver a consistent message: The neuraminidase inhibitors oseltamivir and zanamivir are modestly effective in preventing symptomatic influenza and minimally effective in treating it. Data regarding the much-hyped oseltamivir are particularly damning. In the words of the researchers, “these findings provide reason to question the stockpiling of oseltamivir, its inclusion on the WHO list of essential drugs, and its use in clinical practice as an anti-influenza drug.”