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lies. The median duration of symptoms was 2.5 days shorter in the zanamivir group than in the placebo group (5.0 vs. 7.5 days) (Hayden 2000). A similar risk reduction was shown in a study where zanamivir was administered after close contact with an index case of influenza-like illness (Kaiser 2000).

In a study of inhaled zanamivir for the prevention of influenza in families, 4 % of zanamivir versus 19 % of placebo households had at least 1 contact who developed symptomatic, laboratory-confirmed influenza (81 % protective efficacy). The protective efficacy was similarly high for individuals (82 %) and against both influenza types A and B (78 % and 85 %, respectively, for households) (Monto 2002).

Children

In a trial on children aged five to twelve years, zanamivir reduced the median time to symptom alleviation by 1.25 days compared with placebo. Zanamivir-treated patients returned to normal activities significantly faster and took significantly fewer relief medications than placebo-treated patients (Hedrick 2000).

Zanamivir is therefore safe in children – if they can take it. Children, especially those under 8 years old, are usually unable to use the delivery system for inhaled zanamivir appropriately (not producing measurable inspiratory flow through the diskhaler or producing peak inspiratory flow rates below the 60 l/min considered optimal for the device). As a lack of measurable flow rate is related to inadequate or frankly undetectable serum concentrations, prescribers should carefully evaluate the ability of young children to use the delivery system when considering prescription of zanamivir. When zanamivir is prescribed for children, it should be used only under adult supervision and with attention to proper use of the delivery system (Relenza 2003).

Special Situations

Special settings in which zanamivir has been used include acute lymphoblastic leukemia (Maeda 2002) and allogeneic stem cell transplantation (Johny 2002). The second report found no toxicity attributable to zanamivir and rapid resolution of influenza symptoms. There was no mortality due to influenza in these patients.

Avian Influenza Strains

In a study performed on mice in 2000, zanamivir was shown to be efficacious in treating avian influenza viruses H9N2, H6N1, and H5N1 transmissible to mammals (Leneva 2001).

Resistance

Development of resistance is rare. To date, no virus resistant to zanamivir has been isolated from immunocompetent individuals after treatment. In addition, all zanamivir-resistant strains selected in vitro to date have diminished viability. Known resistance mutations are both influenza virus subtype and drug specific (McKimm-Breschkin 2003).

There is evidence for different patterns of susceptibility and cross-resistance between neuraminidase inhibitors (Mishin 2005, Yen 2005), but no studies have so far evaluated the risk of emergence of cross-resistance in clinical practice.