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Oseltamivir -- A Second Neuraminidase Inhibitor for Influenza

We still do not understand the pathogenesis of epidemic influenza, and our options for treatment and prevention remain limited. A newly developed class of agents, active against both influenza A and B, blocks neuraminidase, the viral enzyme essential to the release of viable viral particles from infected host cells. Zanamivir, the first agent of this class (recently approved for use in Australia, Europe, and the U.S.) is given as an aerosol. Two new manufacturer-sponsored studies detail the prophylactic and therapeutic efficacy of a second neuraminidase inhibitor, oseltamivir, which can be administered orally.

Hayden, Treanor, and coworkers performed 2 randomized, controlled trials to assess the efficacy of oseltamivir in preventing and treating experimental influenza A infection in young, healthy adult volunteers. In a prophylactic trial involving 37 subjects, 100 mg of oseltamivir given either daily or twice daily for 5 days, beginning 26 hours before experimental inoculation, significantly reduced the incidence of symptomatic influenza A. In a similarly designed therapeutic trial with 80 subjects, 4 dose regimens of oseltamivir (from 40 to 400 mg daily, begun 28 hours after inoculation) were compared with placebo. All oseltamivir regimens demonstrated comparable efficacy, and oseltamivir produced significant reductions in peak viral titers, median time to cessation of viral shedding, total symptom scores, nasal mucus production, and nasal lavage fluid cytokine concentrations.

Hayden, Atmar, and coworkers performed 2 identical multicenter, randomized, controlled trials during the 1997 to 1998 influenza season, using 75 mg of oseltamivir, given once or twice daily for 6 weeks, as prophylaxis against naturally occurring influenza. Overall, 1,562 healthy adults were enrolled, and because of an unexpectedly low overall incidence of influenza, data from the two trials were pooled before analysis. Recipients of either oseltmavir regimen had a significantly lower incidence of lab-confirmed influenza-like illness than placebo recipients (1.2% and 1.3% versus 4.8%). The protective efficacy was 74% (95% CI, 53% to 88%). Oseltamivir was generally well tolerated but, compared with placebo, was associated with a higher incidence of nausea (12.1% and 14.6% vs. 7.1%) and vomiting (2.5% and 2.7% vs. 0.8%), primarily in the first week of the study.

Comment: Zanamivir may produce bronchospasm in patients with asthma or COPD. Thus, although the relative efficacy of zanamivir and oseltamivir has not been directly compared, it appears that oseltamivir will be an attractive alternative for preventing influenza. The use of either agent should complement but not supplant the use of influenza vaccine as a preventive measure.

— R Ellison

Published in Journal Watch Infectious Diseases December 1, 1999

Citation(s):

Hayden FG, Treanor JJ, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza. Randomized controlled trials for prevention and treatment. JAMA 1999 Oct 06 282 1240 -1246.

• Original article (Subscription may be required)
• Medline abstract (Free)

Hayden FG, Atmar RL, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med 1999 Oct 28 341 1336 -1343.

• Original article (Subscription may be required)
• Medline abstract (Free)

Cox NH and Hughes JM. New options for the prevention of influenza. N Engl J Med 1999 Oct 28 282 1387 -1388.