Inhaled zanamivir for the prevention of influenza in families.

Background: As prophylaxis against influenza in families, amantadine and ri mantadine have had inconsistent effectiveness, partly because of the transm ission of drug-resistant variants from treated index patients. We performed a double-blind, placebo-controlled study of inhaled zanamivir for the trea tment and prevention of influenza in families. Methods: We enrolled families (with two to five members and at least one ch ild who was five years of age or older) before the 1998-1999 influenza seas on. If an influenza-like illness developed in one member, the family was ra ndomly assigned to receive either inhaled zanamivir or placebo. The family member with the index illness was treated with either 10 mg of inhaled zana mivir (163 subjects) or placebo (158) twice a day for 5 days, and the other family members received either 10 mg of zanamivir (414 subjects) or placeb o (423) once a day as prophylaxis for 10 days. The primary end point was th e proportion of families in which at least one household contact had sympto matic, laboratory-confirmed influenza. Results: The proportion of families with at least one initially healthy hou sehold contact in whom influenza developed was smaller in the zanamivir gro up than in the placebo group (4 percent vs. 19 percent, P<0.001); the diffe rence represented a 79 percent reduction in the proportion of families with at least one affected contact. Zanamivir provided protection against both influenza A and influenza B. A neuraminidase-inhibition assay and sequencin g of the neuraminidase and hemagglutinin genes revealed no zanamivir-resist ant variants. Among the subjects with index cases of laboratory-confirmed i nfluenza, the median duration of symptoms was 2.5 days shorter in the zanam ivir group than in the placebo group (5.0 vs. 7.5 days, P=0.01). Zanamivir was well tolerated. Conclusions: When combined with the treatment of index cases, prophylactic treatment of family members with once-daily inhaled zanamivir is well toler ated and prevents the development of influenza. In this study there was no evidence of the emergence of resistant influenza variants. (N Engl J Med 20 00;343:1282-9.) (C) 2000, Massachusetts Medical Society.