What is the use of Amantadine (antiviral medication) in pediatric patients with influenza A virus infections?

Use of Amantadine in Children with Influenza A

Amantadine is no longer recommended for treatment or prophylaxis of influenza A in children due to high levels of viral resistance, with neuraminidase inhibitors being the preferred antiviral agents for pediatric influenza management. 1

Historical Approved Use

Amantadine was previously FDA-approved for:

• Treatment and prophylaxis of influenza A virus infections in children ≥1 year of age 2
• Dosing for children 1-9 years: 5-8 mg/kg/day as single daily dose or in 2 doses, not to exceed 150 mg/day 3
• Dosing for children 9-12 years: 200 mg/day in 2 doses 3

Mechanism and Limitations

Amantadine works by interfering with the replication cycle of type A influenza viruses through inhibition of the M2 ion channel 1. However, its use is severely limited by:

1. High resistance rates: Approximately 92% of circulating influenza A virus isolates demonstrated resistance to adamantanes by 2008 1
2. Limited spectrum: Only effective against influenza A viruses with no activity against influenza B 1, 4
3. Rapid resistance development: Drug-resistant viruses emerge quickly during therapy, with resistant variants detected in approximately 30% of treated patients within 2-3 days 5
4. Side effects: Higher incidence of adverse central nervous system reactions compared to newer antivirals, including insomnia, decreased concentration, and dizziness in 5-33% of recipients 1, 5

Current Recommendations

The Advisory Committee on Immunization Practices (ACIP) and other authorities have established that:

• Amantadine should only be used for treatment and prophylaxis during winter seasons when a majority of influenza A virus strains are adamantane-susceptible 3
• Neuraminidase inhibitors (oseltamivir and zanamivir) are now preferred for influenza treatment in children due to:
  • Activity against both influenza A and B viruses 3
  • Lower rates of resistance development 1
  • Fewer CNS side effects 1
  • Demonstrated reduction in complications such as otitis media 1

Efficacy Data in Children

Limited studies have shown:

• Amantadine showed prophylactic effect against influenza A infection in children 6
• Efficacy in prevention of serologically confirmed clinical influenza was reported as 70.7% in one study 7
• However, a Cochrane review found insufficient evidence to make definitive conclusions about safety and effectiveness in children 6

Clinical Decision Algorithm

When considering antiviral therapy for influenza in children:

1. First-line agents: Use neuraminidase inhibitors (oseltamivir or zanamivir based on age)

   • Oseltamivir: Approved for treatment in children ≥1 year
   • Zanamivir: Approved for treatment in children ≥7 years

2. When to consider amantadine (rarely):

   • Only if neuraminidase inhibitors are unavailable
   • Only during seasons when surveillance data confirms low resistance rates
   • Only for influenza A (not effective for influenza B)
   • Must be started within 48 hours of symptom onset

3. Contraindications to amantadine:

   • Children <1 year of age
   • Known resistance patterns in circulating strains
   • History of adverse reactions to amantadine
   • Seizure disorders or other CNS conditions

Important Caveats

• Antiviral drugs are an adjunct to vaccination and should not be considered a substitute 3
• Annual influenza vaccination remains the primary strategy for prevention 1
• Treatment with antivirals is most effective when started within 48 hours of symptom onset 1

In conclusion, while amantadine was historically used for influenza A treatment and prophylaxis in children, current guidelines strongly favor neuraminidase inhibitors due to widespread resistance to amantadine and its limited spectrum of activity.