EFFICACY AND SAFETY OF THE NEURAMINIDASE INHIBITOR ZANAMIVIR IN THE TREATMENT OF INFLUENZA-VIRUS INFECTIONS

Background The sialic acid analogue zanamivir (GG167) is a selective i nhibitor of influenza A and B virus neuraminidases. These viral enzyme s are essential for the release of virus from infected cells, and they may also reduce the inactivation of virus by respiratory secretions. When administered experimentally directly to the respiratory tract, za namivir has potent antiviral effects. We assessed the therapeutic acti vity of zanamivir in adults with acute influenza. Methods We conducted separate randomized, double-blind studies in 38 centers in North Amer ica and 32 centers in Europe during the influenza season of 1994-1995. A total of 417 adults with influenza-like illness of less than or equ al to 48 hours' duration were randomly assigned to one of three treatm ents: 6.4 mg of zanamivir by intranasal spray plus 10 mg by inhalation , 10 mg of zanamivir by inhalation plus placebo spray, or placebo by b oth routes. Treatments were self-administered twice daily for five day s. Results Of 262 patients with confirmed influenzavirus infection (63 percent of all patients), the median length of time to the alleviatio n of all major symptoms was one day shorter (four days vs. five days) in the 88 patients given inhaled and intranasal zanamivir (P=0.02) and the 85 patients given inhaled zanamivir alone (P=0.05) than in the 89 patients given placebo. Among the infected patients who were febrile at enrollment and among those who began treatment within 30 hours afte r the onset of symptoms, the median time to the alleviation of major s ymptoms was four days in both zanamivir groups and seven days in the p lacebo group (P less than or equal to 0.01). Viral titers of nasal was hings in the group given inhaled and intranasal zanamivir were signifi cantly lower than those in the placebo group. The topically administer ed zanamivir was well tolerated. Conclusions In adults with influenza A or B virus infections, direct administration of a selective neuramin idase inhibitor, zanamivir, to the respiratory tract is safe and reduc es symptoms if begun early. (C) 1997, Massachusetts Medical Society.