Spotlight on zanamivir in influenza

Abstract

Zanamivir is a potent competitive inhibitor of the neuraminidase glycoprotein, which is essential in the infective cycle of influenza A and B viruses. Zanamivir (10 mg by inhalation via the Diskhaler twice daily, or 10 mg inhaled plus 6.4 mg intranasally 2 or 4 times daily, for 5 days) reduced the median time to alleviation of major influenza symptoms by up to 2.5 days compared with placebo. Significant reductions of 1 to 2.5 days versus placebo were observed with inhaled zanamivir in phase III trials involving otherwise healthy adults, high-risk patients or children aged 5 to 12 years. Accelerated return to normal activities, and reduced interference with sleep, consumption of relief medication and incidence of complications leading to antibacterial use were also observed with zanamivir. When used for prophylaxis, inhaled zanamivir 10 to 20 mg/day for 10 days to 4 weeks (plus 6.4 mg/day intranasally in one trial) prevented influenza A in 67% of recipients in a university community, significantly reduced the number of families with new cases of influenza compared with placebo or prevented new cases of influenza in long-term care facilities. The tolerability of inhaled or intranasal zanamivir was similar to that of placebo in otherwise healthy adults, high-risk and elderly patients, and children. Recommended dosages of zanamivir did not adversely affect pulmonary function in patients with respiratory disorders in a well-controlled trial, although there have been rare reports of bronchospasm and/or a decline in respiratory function. In conclusion, zanamivir (used within 48 hours of symptom development) reduces the duration of symptomatic illness, causes accelerated return to normal activities or reduces complications requiring antibacterial use in adults, high-risk individuals and children with influenza. Vaccination remains the intervention of choice for prophylaxis in selected populations. However, the efficacy, good tolerability profile and lack of resistance with zanamivir make it a useful option, particularly in those not covered or inadequately protected by vaccination, who are able to use the inhalation device. The use of zanamivir in patients with respiratory disorders remains unclear because of concerns regarding its potential for bronchospasm. Prospective cost-effectiveness analyses and investigations of efficacy in preventing serious complications of influenza, particularly in high-risk patients, are required. Zanamivir shows potential for prophylaxis in persons for whom vaccination is contraindicated or ineffective, in elderly or high-risk patients in long-term care facilities and in households.