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Review says oseltamivir and zanamivir should be kept for epidemics of flu

BMJ 2006; 332 doi: (Published 26 January 2006) Cite this as: BMJ 2006;332:196
  1. Susan Mayor
  1. London

    The neuraminidase inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) may be effective in serious epidemic or pandemic influenza but must be used together with infection control procedures, says a Cochrane review published last week. The review said that these drugs should not be used for seasonal flu but should be kept for serious epidemics and that other antivirals should not be used at all for flu.

    The review, which was published online ahead of print publication on 19 January in the Lancet (, doi: 10.1016/S0140-6736(06)67970-1), analysed data from randomised controlled trials of both classes of antivirals currently used to prevent or treat flu: the M2 ion channel inhibitors, amantadine and rimantadine, and two of the newer neuraminidase inhibitors, zanamivir and oseltamivir. The researchers identified trials by searching databases and contacting manufacturers of antivirals for all data available up to October 2005 from trials that used the drugs to prevent or treat symptomatic or asymptomatic flu in healthy adults. Fifty three trials were included in the review: 19 looked at neuraminidase inhibitors and 34 at the M2 ion channel inhibitors.

    The review showed that the neuraminidase inhibitors reduced flu symptoms and interrupted transmission of seasonal flu, in addition to reducing nasal shedding. However, they did not prevent asymptomatic infection.

    When used in prophylaxis, oral oseltamivir (75 mg daily) prevented 61% (95% confidence interval 15% to 82%) of cases of symptomatic flu, increasing to 73% (33% to 89%) at a higher dose (150 mg daily). Inhaled zanamivir (10 mg daily) prevented 62% of cases (15% to 83%).

    When used as prophylaxis after exposure to people with flu, oseltamivir prevented infection in 59% (16% to 80%) of people undergoing household exposure and protected 68% (35% to 84%) to 89% (67% to 97%) of contacts of index cases.

    When used to treat flu, oseltamivir alleviated symptoms significantly more quickly than placebo, as long as treatment was started within 48 hours of the onset of symptoms. Oseltamivir at a dose of 150 mg daily was also effective in preventing complications in the lower respiratory tract in flu cases (odds ratio 0·32 (0·18 to 0·57). The neuraminidase inhibitors reduced viral nasal titres by around two thirds (weighted mean difference - 0·62 (- 0·82 to - 0·41)).

    M2 ion channel inhibitors reduced symptoms of the type A influenza but failed to prevent infection or viral shedding. Amantadine shortened the duration of fever, when compared with placebo (by 0·99 (1.26 to 0.71) days) but had no effect on nasal shedding of type A viruses (relative risk 0·93 (0·71 to 1·21)). The data showed similar effects for rimantadine.

    Amantadine was associated with a relatively high rate of side effects, including nausea (odds ratio 2·6 (1·4 to 4·8) and insomnia and hallucinations (2·5 (1·5 to 4·3)). Withdrawal from treatment because of adverse events were also common (odds ratio 2·5 (1·6 to 4·1)). Oseltamivir was associated with nausea (odds ratio 1·8 (1·1 to 2·9)), especially at higher prophylactic doses (odds ratio 2·3 (1·3 to 3·9).

    Tom Jefferson, lead author of the study and coordinator of the Cochrane Vaccines Field, which is based in Rome, concluded, “The use of amantadine and rimantadine should be discouraged. Because of their low effectiveness against influenza-like illness, neuraminidase inhibitors should not be used in seasonal influenza control and should only be used in a serious epidemic or pandemic alongside other public health measures, including hand washing and avoiding contact with other people.”

    He said that even though neuraminidase inhibitors reduced viral shedding, they did not completely stop it, so people treated with the drugs could still be infectious and should take steps to avoid transmitting the virus.

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