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arznei-telegramm 2006; 37: 22

 


Influenza: Are antiviral agents overrated? A systematic review of the benefit of antiviral agents in prevention and treatment of influenza in healthy adults has recently caused a stir; the authors, members of a COCHRANE working group, came to the conclusion that the neuraminidase inhibitor oseltamivir (TAMIFLU) and zanamivir (RELENZA) should not be used at all because of their small benefit in controlling conventional seasonal influenza. In a serious epidemic or pandemic they should only be used together with further protective measures such as wearing gloves or face masks. The authors advise fully against the older virostatics amantadine (e.g. AMANTADIN-CT; see also page 23) and rimantadine (not on the market in Germany), which are effective only against influenza A. The meta-analysis included a total of 53 randomised studies, 19 with neuraminidase inhibitors and 34 with amantadine or rimantadine. Apart from rimantadine, for which there are comparatively few data, no major differences were found between the other drugs: as prophylactic agents they prevent about 60% of influenza A infections. Asymptomatic infections, on the other hand, are not influenced. A certain protection against flu-like illness is only proven for amantadine (protection rate 25%, 95% confidence interval 13-36). Used therapeutically in influenza amantadine and rimantadine shorten the duration of fever by one day. This corresponds roughly to the known effect of neuraminidase inhibitors (cf. a-t 2005; 36: 62-3, 2002; 33: 98-9). However, the benefit of the two substance groups cannot be compared directly in this analysis as the results for neuraminidase inhibitors are represented as the hazard ratio (HR) for not spezified method-related reasons (HR 1.30 [oseltamivir] and 1.28 [zanamivir] respectively).* A crucial point for the authors is the influence on the nasal virus concentration: No effect could be detected after five days of use with either amantadine or rimantadine on virus shedding with the nasal secretion and persistence of the pathogens in the airways. On the other hand neuraminidase inhibitors reduce the average nasal virus titres measured 24 hours and 48 hours after randomisation. In addition, nausea and other gastrointestinal side effects, sleep disturbances, hallucinations and therapy discontinuations because of unwanted effects occur markedly more often with amantadine than in the control groups, especially with prophylactic use. Nausea is observed significantly more often when oseltamivir is taken prophylactically (JEFFERSON, T. et al.: Lancet 2006, 367: 303-13/ati d). The systematic review has some method-related deficiencies. For instance, studies are included where it is unclear whether they were actual randomised. Different dosages, some not licensed, are also evaluated in one group. Whether the difference emphasised by the authors in the effect on nasal virus concentrations, which were measured at different times, are actually present and clinically relevant in the sense of diminished infectivity, remains open. The supposed better tolerability of oseltamivir can be reliably assessed only when it is used more widely, as the recently published reports of suspected neuropsychiatric effects and suicidal tendencies show (a-t 2005; 36: 113-4), -ed.


*

The time to alleviation of symptoms is shown. HR > 1 means an advantage for the treatment group.



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