Managing influenza: amantadine, rimantadine and beyond.

Amantadine and rimantadine are effective in the treatment and prophylaxis of influenza A. Neither drug, however, has achieved widespread acceptance because of the rapid development of viral resistance, their lack of activity against influenza B and, in the case of amantadine, adverse events. Complete cross-resistance occurs with these compounds and is associated with a single nucleotide change in the M2 protein. Resistant variants are transmissible and fully pathogenic. Zanamivir is the first widely approved neuraminidase inhibitor for the treatment of influenza. It is delivered directly to the primary site of viral replication, the respiratory tract, and is well tolerated and effective in the treatment of both influenza A and B. Data in prophylaxis are also encouraging. During the extensive clinical programme no evidence for the emergence of drug-resistant strains with acute therapy was found. Zanamivir represents a significant advance over older agents in the management of influenza A and B.