Table 1.
Approved antiviral agents for influenza
| Characteristics | M2 Inhibitors | NA Inhibitors | ||
|---|---|---|---|---|
| Amantadine | Rimantadine | Zanamivir | Oseltamivir | |
| FDA approved |
1966 Symmetrel |
1993 Flumadine |
1999 Relenza |
1999 Tamiflu |
| Efficacy | Influenza A virus infection | Influenza A and B virus infection | ||
|
Treatment regimen (adults) |
100 mg orally bid × 5 days |
100 mg orally bid × 5 days |
2 inhaled doses (10 mg) bid × 5 days |
75 mg orally bid × 5 days |
|
Treatment regimen (children) |
5 mg/kg/d orally (max 150 mg/d) in 2 doses × 5 days | 5 mg/kg/d orally (max 150 mg/d) in 2 doses × 5 days |
>7 years 2 inhalaled doses (10 mg) bid × 5 days |
>1 year 12–75 mg orally bid × 5 days |
| Prophylaxis regimen (adults) |
100 mg orally bid |
100 mg orally bid |
2 inhalaled doses (10 mg) qd × 10 days |
75 mg orally qd × 10 days |
| Prophylaxis regimen (children) |
5 mg/kg/d orally (max 150 mg/d) in 2 doses |
5 mg/kg/d orally (max 150 mg/d) in 2 doses |
>5 years 2 inhalat. (10 mg) qd × 10 days |
>1 year 12–75 mg orally qd × 10 days |
|
Adverse effects |
Nausea, dizziness, insomnia, vomiting, nervousness, light headedness, impaired concentration, seizures | Nausea, dizziness, insomnia, vomiting, light headedness; less pronounced CNS adverse effects | Bronchospasm | Nasal congestion, nausea, vomiting, discomfort |
| Mechanism of action | Inhibit viral replication by blocking the ion channel at the stage of virus entry into cells; prevent virus release by altering the conformation of the HA protein | Block the activity of the NA enzyme and interrupt an established infection at a later stage of virus replication by inhibiting the release of virions from infected cells | ||
| Molecular markers of resistancea | Mutations in M2 protein at positions: L26F; V27A/T/S/G; A30V/T/S; S31N/G; G34E |
Mutations in NA: Q136K (N1and N2 subtypes); E119D/G/A (B virus) |
Mutations in NA: H275Y, N295S (N1 subtype); E119V, R292K (N2 subtype); R152K, D198N (B virus) | |
Note N1 and N2 numbering is used to designated NA mutations in corresponding NA subtypes of influenza A viruses; N2 numbering is used to designated NA mutations for influenza B viruses.aBased on sequence analysis of M gene (M2 inhibitors) or NA gene (NA inhibitors). Q136KNA mutation has been reported in MDCK-propagated clinical isolates of seasonal H1N1 and H3N2 viruses with the reduced susceptibility to zanamivir (Hurt et al. 2009; Dapat et al. 2010)