Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza

Background Safe and effective antiviral agents are needed to prevent infect ion with influenza A and B viruses. Oseltamivir (GS4104), which can be admi nistered orally, is the prodrug of GS4071, a potent and selective inhibitor of influenzavirus neuraminidases. We studied the use of oseltamivir for lo ngterm prophylaxis against influenza in two placebo-controlled, double-blin d trials at different U.S. sites during the winter of 1997-1998. Methods We randomly assigned 1559 healthy, nonimmunized adults 18 to 65 yea rs old to receive either oral oseltamivir (75 mg given once or twice daily, for a total daily dose of 75 or 150 mg) or placebo for six weeks during a peak period of local influenzavirus activity. The primary end point with re spect to efficacy was laboratory-confirmed influenza-like illness (defined as a temperature of at least 37.2 degrees C accompanied by at least one res piratory and at least one systemic symptom). Results In the two studies combined, the risk of influenza among subjects a ssigned to either once-daily or twice-daily oseltamivir (1.2 percent and 1. 3 percent, respectively) was lower than that among subjects assigned to pla cebo (4.8 percent; P<0.001 and P=0.001 for the comparison with once-daily a nd twice-daily oseltamivir, respectively). The protective efficacy of oselt amivir in the two active-treatment groups combined was 74 percent (95 perce nt confidence interval, 53 to 88 percent) at all the sites combined and 82 percent (95 percent confidence interval, 60 to 93 percent) at sites in Virg inia, where the rate of influenza infection was higher than the overall rat e. For culture-proved influenza, the rate of protective efficacy in the two oseltamivir groups combined was 87 percent (95 percent confidence interval , 65 to 96 percent). The rate of laboratory-confirmed influenza infection w as lower with oseltamivir than with placebo (5.3 percent vs. 10.6 percent, P<0.001). Oseltamivir was well tolerated but was associated with a greater frequency of nausea (12.1 percent and 14.6 percent in the once-daily and tw ice-daily groups, 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 discontinuation of drug or placebo wa s similar among the three groups (3.1 to 4.0 percent). Conclusions Oseltamivir administered daily for six weeks by the oral route is safe and effective for the prevention of influenza. (N Engl J Med 1999;3 41: 1336-43.) (C) 1999, Massachusetts Medical Society.