Use of the Selective Oral Neuraminidase Inhibitor Oseltamivir to Prevent Influenza
Frederick G. Hayden, M.D., Robert L. Atmar, M.D., Margo Schilling, M.D., Casey Johnson, D.O., Donald Poretz, M.D., David Paar, M.D., Les Huson, Ph.D., Penelope Ward, M.D., Roger G. Mills, M.D., for The Oseltamivir Study Group
Background Safe and effective antiviral agents are needed toprevent infection with influenza A and B viruses. Oseltamivir(GS4104), which can be administered orally, is the prodrug ofGS4071, a potent and selective inhibitor of influenzavirus neuraminidases.We studied the use of oseltamivir for long-term prophylaxisagainst influenza in two placebo-controlled, double-blind trialsat different U.S. sites during the winter of 1997–1998.
Methods We randomly assigned 1559 healthy, nonimmunized adults18 to 65 years old to receive either oral oseltamivir (75 mggiven once or twice daily, for a total daily dose of 75 or 150mg) or placebo for six weeks during a peak period of local influenzavirusactivity. The primary end point with respect to efficacy waslaboratory-confirmed influenza-like illness (defined as a temperatureof at least 37.2°C accompanied by at least one respiratoryand at least one systemic symptom).
Results In the two studies combined, the risk of influenza amongsubjects assigned to either once-daily or twice-daily oseltamivir(1.2 percent and 1.3 percent, respectively) was lower than thatamong subjects assigned to placebo (4.8 percent; P<0.001and P=0.001 for the comparison with once-daily and twice-dailyoseltamivir, respectively). The protective efficacy of oseltamivirin the two active-treatment groups combined was 74 percent (95percent confidence interval, 53 to 88 percent) at all the sitescombined and 82 percent (95 percent confidence interval, 60to 93 percent) at sites in Virginia, where the rate of influenzainfection was higher than the overall rate. For culture-provedinfluenza, the rate of protective efficacy in the two oseltamivirgroups combined was 87 percent (95 percent confidence interval,65 to 96 percent). The rate of laboratory-confirmed influenzainfection was lower with oseltamivir than with placebo (5.3percent vs. 10.6 percent, P<0.001). Oseltamivir was welltolerated but was associated with a greater frequency of nausea(12.1 percent and 14.6 percent in the once-daily and twice-dailygroups, respectively) and vomiting (2.5 percent and 2.7 percent,respectively) than was placebo (nausea, 7.1 percent; vomiting,0.8 percent). However, the frequency of premature discontinuationof drug or placebo was similar among the three groups (3.1 to4.0 percent).
Conclusions Oseltamivir administered daily for six weeks bythe oral route is safe and effective for the prevention of influenza.
Source Information
From the University of Virginia, Charlottesville (F.G.H.); Baylor College of Medicine, Houston (R.L.A.); Eastern Virginia Medical School, Norfolk (M.S.); Pharmaceutical Research Associates, Lenexa, Kans. (C.J.); Infectious Diseases Physicians, Fairfax, Va. (D. Poretz); University of Texas, Galveston (D. Paar); Roche Global Development, Welwyn, United Kingdom (L.H., P.W.); and Gilead Sciences, Foster City, Calif. (R.G.M.).
Address reprint requests to Dr. Hayden at the Department of Medicine, Box 473, University of Virginia Health Sciences Center, Charlottesville, VA 22908.
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