Inhaled Zanamivir for the Prevention of Influenza in Families
Frederick G. Hayden, M.D., Larisa V. Gubareva, Ph.D., Arnold S. Monto, M.D., Thomas C. Klein, M.D., Michael J. Elliott, M.D., Janet M. Hammond, M.D., Ph.D., Stephen J. Sharp, M.A., Michael J. Ossi, M.D., for The Zanamivir Family Study Group
Background As prophylaxis against influenza in families, amantadineand rimantadine have had inconsistent effectiveness, partlybecause of the transmission of drug-resistant variants fromtreated index patients. We performed a double-blind, placebo-controlledstudy of inhaled zanamivir for the treatment and preventionof influenza in families.
Methods We enrolled families (with two to five members and atleast one child who was five years of age or older) before the1998–1999 influenza season. If an influenza-like illnessdeveloped in one member, the family was randomly assigned toreceive either inhaled zanamivir or placebo. The family memberwith the index illness was treated with either 10 mg of inhaledzanamivir (163 subjects) or placebo (158) twice a day for 5days, and the other family members received either 10 mg ofzanamivir (414 subjects) or placebo (423) once a day as prophylaxisfor 10 days. The primary end point was the proportion of familiesin which at least one household contact had symptomatic, laboratory-confirmedinfluenza.
Results The proportion of families with at least one initiallyhealthy household contact in whom influenza developed was smallerin the zanamivir group than in the placebo group (4 percentvs. 19 percent, P<0.001); the difference represented a 79percent reduction in the proportion of families with at leastone affected contact. Zanamivir provided protection againstboth influenza A and influenza B. A neuraminidase-inhibitionassay and sequencing of the neuraminidase and hemagglutiningenes revealed no zanamivir-resistant variants. Among the subjectswith index cases of laboratory-confirmed influenza, the medianduration of symptoms was 2.5 days shorter in the zanamivir groupthan in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivirwas well tolerated.
Conclusions When combined with the treatment of index cases,prophylactic treatment of family members with once-daily inhaledzanamivir is well tolerated and prevents the development ofinfluenza. In this study there was no evidence of the emergenceof resistant influenza variants.
Source Information
From the University of Virginia, Charlottesville (F.G.H., L.V.G.); the University of Michigan, Ann Arbor (A.S.M.); Heartland Research, Wichita, Kans. (T.C.K.); Glaxo Wellcome, Research Triangle Park, N.C. (M.J.E., J.M.H., M.J.O.); and Glaxo Wellcome Research and Development, Greenford, United Kingdom (S.J.S.).
Address reprint requests to Dr. Hayden at the University of Virginia, Health Sciences Center, Box 800473, Charlottesville, VA 22908.
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