Role of combination antiviral therapy in pandemic influenza and stockpiling implications

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Sotirios Tsiodras, lecturer in infectious diseases1,
John D Mooney, public health specialist trainee2,
Angelos Hatzakis, professor3

¹Fourth Academic Department of Internal Medicine, University of Athens Medical School, Athens 12462, Greece
²South West Public Health Training Programme, Dorset
³Department of Hygiene and Epidemiology, University of Athens Medical School

Correspondence to: S Tsiodras tsiodras{at}med.uoa.gr

Accepted 16 January 2007

It is impossible to predict which drugs will be effective against a new pandemic strain of influenza. Sotirios Tsiodras and colleagues argue that failure to stockpile both major classes of antiviral drugs could prove costly

We currently have two classes of drugs that are effective against influenza viruses: the M2 ion channel inhibitors (amantadine and rimantadine) and the neuraminidase inhibitors (oseltamivir, zanamivir).1 Although ion channel inhibitors are effective against several subtypes of influenza A viruses,2 they are not being widely stockpiled for a future influenza pandemic.3 This is because they cause unacceptable side effects1 and their use is associated with a rapid emergence of resistance1 4 5 without any demonstrable reduction in transmissibility or pathogenicity.6 Resistance of influenza A viruses to amantadine is increasing worldwide,7 and the US Centers for Disease Control and Prevention recommended against the use of ion channel inhibitors for treatment or prophylaxis during the 2005-6 influenza season.8 Policy makers and some medical experts thus consider ion channel inhibitors inappropriate as first line treatment or prophylaxis for pandemic influenza. We believe their role should be reconsidered for three reasons: firstly, the unpredictability of antiviral susceptibility in …