Influenza is a highly contagious and debilitating disease that imposes an excess 
burden of complications and mortality. Antiviral therapy is the primary 
intervention for treatment and post-exposure prophylaxis (PEP) of influenza. 
Amantadine and rimantadine are members of the M2 class of antiviral agents and 
are moderately effective in influenza management. However, their utility is 
compromised by high levels of resistance, tolerability concerns and a lack of 
efficacy against influenza B. An alternative class of agents, the neuraminidase 
inhibitors (NIs), represent the most advanced form of antiviral therapy 
available, and act by specifically inhibiting the neuraminidase enzymes that are 
present on all influenza subtypes. Two NIs, oseltamivir and zanamivir, are 
currently available for clinical use. Oseltamivir, the most widely used NI, is 
administered orally as a prodrug (oseltamivir carboxylate) and systemically 
distributed to all potential infection sites. Zanamivir, a second NI, is 
administered by inhalation via a disk inhaler and deposited primarily in the 
respiratory tract. When administered within 48 hours of symptom onset, both 
agents significantly reduce illness duration and symptom severity, and decrease 
the rate of influenza-associated complications. With oseltamivir, greater 
benefits are detected with earlier treatment initiation (<12 hours). In PEP, 
both NIs effectively protect the close contacts of index cases from symptomatic 
influenza. Oseltamivir and zanamivir are generally well tolerated and associated 
with a low level of resistance. Emerging evidence supports the activity of both 
NIs against the H5N1avian influenza infection, which is a pandemic candidate. 
However, the WHO currently recommends the use of oseltamivir for the management 
of suspected cases, given the systemic nature of the H5N1 challenge. Ongoing 
studies are exploring the effectiveness of oseltamivir, zanamivir and other NIs 
for pandemic management.