Amantadine Should NOT Be Used for Influenza
Amantadine is no longer recommended for the treatment or prevention of influenza due to widespread viral resistance, and should not be used in clinical practice. 1
Current Status and Resistance
The adamantane class of antivirals (amantadine and rimantadine) has been rendered essentially obsolete by rapidly emerging resistance:
- Resistance rates reached approximately 99% among influenza A(H3N2) isolates and 10% among influenza A(H1N1) isolates by the 2007-08 season 1
- This represents a dramatic increase from only 0.4% resistance during 1994-1995 to 12.3% during 2003-2004, with 92% of H3N2 viruses showing resistance by 2005-06 1
- Amantadine has zero activity against influenza B virus 1, 2
Mechanism and Historical Efficacy
While amantadine works by blocking the M2 ion channel protein essential for viral replication 2, its historical efficacy is now clinically irrelevant:
- Previously prevented 61% of influenza A cases and 25% of influenza-like illness 3
- Reduced fever duration by approximately one day when used for treatment 3
- Required administration within 48 hours of symptom onset 2
Critical Limitations
Common pitfalls to avoid:
- Do not prescribe amantadine as monotherapy for influenza under any circumstances 1
- Resistance develops rapidly (within 2-3 days of treatment) in approximately 30% of treated patients 4
- Resistant viruses are fully transmissible and pathogenic 5
Adverse Effects
Amantadine causes significant side effects that further limit its utility:
- Gastrointestinal effects (nausea) with OR 2.56 6
- Central nervous system effects including insomnia and hallucinations (OR 2.54) 6
- Higher withdrawal rates due to adverse events compared to rimantadine 3
Extremely Limited Exception
The only scenario where amantadine might be considered is in combination with a neuraminidase inhibitor (never alone) when oseltamivir-resistant viruses are widespread AND zanamivir cannot be used (e.g., critically ill patients who cannot use inhaled medications, or young children outside zanamivir's licensed age range) 1. This requires:
- Consultation with local health authorities first 1
- Confirmation that local surveillance shows oseltamivir resistance
- Documentation that the resistant strain is susceptible to adamantanes 1
Current Recommendations
Use neuraminidase inhibitors (oseltamivir or zanamivir) instead - these remain the only recommended antivirals for influenza treatment and prophylaxis 1, 7. Amantadine should only be used when all other measures fail and only in the specific combination scenario described above 3.