What is the efficacy of amantadine (Adamantane) in treating influenza in humans?

Amantadine Is Not Effective for Treating Influenza in Humans

Amantadine should not be used as a first-line treatment for influenza due to widespread viral resistance and lack of efficacy against current circulating strains. 1

Evidence Against Amantadine Efficacy

Resistance Patterns

• Adamantane resistance among influenza A viruses has increased dramatically worldwide:
  • From 0.4% during 1994-1995 to 12.3% during 2003-2004 1
  • By 2005-2006,92% of influenza A (H3N2) viruses demonstrated resistance 1
  • By 2007-2008, approximately 99% of tested influenza A (H3N2) and 10% of influenza A (H1N1) isolates were resistant to adamantanes 1
  • Resistance continues to evolve with viral mutations, particularly in the M2 protein 2

Treatment Recommendations

• The WHO Rapid Advice Guidelines (2007) explicitly state: "If neuraminidase inhibitors are available, clinicians should not administer amantadine alone as a first-line treatment to patients with confirmed or strongly suspected human infection with avian influenza" 1
• This recommendation is based on the high value placed on avoiding resistance development and adverse effects 1
• ACIP (Advisory Committee on Immunization Practices) has recommended against using amantadine for influenza prevention or treatment unless part of a combination regimen with a neuraminidase inhibitor 1

Limited Efficacy Data

• No high-quality evidence exists for amantadine's efficacy in preventing complications of influenza A among high-risk persons 1
• A 2014 Cochrane review concluded that the quality of evidence combined with limited benefits of amantadine and rimantadine do not indicate usefulness in preventing, treating, or shortening the duration of influenza A in children and the elderly 3
• The FDA label notes: "There is no clinical evidence indicating that amantadine hydrochloride is effective in the prophylaxis or treatment of viral respiratory tract illnesses other than those caused by influenza A virus strains" 4

When Amantadine Might Be Considered

In very limited circumstances, amantadine might be considered:

1. When neuraminidase inhibitors (oseltamivir, zanamivir) are not available 1
2. When the virus is known or likely to be susceptible to amantadine 1
3. As part of a combination therapy with a neuraminidase inhibitor when oseltamivir resistance is suspected 1

Side Effects and Limitations

• Central nervous system side effects occur in 5-10% of patients receiving standard doses:
  • Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness 4
  • More serious CNS effects (seizures, confusion) can occur, especially in elderly, those with renal disease, or seizure disorders 4
• Gastrointestinal side effects include anorexia and nausea 4
• Rapid development of viral resistance is a major concern 5
• Complete cross-resistance occurs between amantadine and rimantadine 5
• Resistant variants are transmissible and fully pathogenic 5

Preferred Alternatives

Neuraminidase inhibitors (oseltamivir and zanamivir) are preferred for influenza treatment because:

• They are effective against both influenza A and B 1
• They have lower rates of resistance development 5
• They demonstrate better efficacy in reducing the duration of illness 1
• They have more favorable side effect profiles 5

In conclusion, the evidence clearly shows that amantadine is no longer effective for treating most circulating influenza strains due to widespread resistance, and its use should be limited to specific circumstances where susceptibility is known and better alternatives are unavailable.