Amantadine: Use and Dosage
Influenza A Prophylaxis and Treatment
Amantadine is 70-90% effective for preventing influenza A illness and can reduce severity and duration when started within 24-48 hours of symptom onset, but it has NO proven efficacy in preventing serious complications like pneumonia. 1
Standard Adult Dosing for Influenza A
- Treatment and prophylaxis: 200 mg daily (100 mg twice daily or as single dose) 2
- Persons ≥65 years: Maximum 100 mg daily due to declining renal function with age 1
- Split dosing (100 mg twice daily) may reduce CNS side effects compared to once-daily dosing 2
Pediatric Dosing for Influenza A
- Ages 1-9 years: 5 mg/kg/day (not to exceed 150 mg/day) in divided doses 1
- Ages ≥10 years and weight ≥40 kg: 200 mg daily (100 mg twice daily) 1
- Ages ≥10 years but weight <40 kg: 5 mg/kg/day regardless of age 1
- Not adequately studied in children <1 year 2
Treatment Duration and Timing
- Prophylaxis: Continue for at least 10 days after known exposure, or 2-4 weeks after vaccination until protective antibodies develop, or for duration of community influenza activity 2
- Treatment: Discontinue 24-48 hours after symptom resolution, typically 3-5 days total to minimize resistance emergence 1
- Must start treatment within 24-48 hours of symptom onset for efficacy 2
Parkinson's Disease
For Parkinson's disease, amantadine 100 mg twice daily (200 mg/day) is the standard dose, with onset of action typically within 48 hours. 2
Parkinson's Dosing Algorithm
- Initial dose in medically complex patients: 100 mg once daily for 1-several weeks 2
- Standard maintenance: 100 mg twice daily (200 mg/day) 2
- Maximum dose for non-responders: 400 mg daily in divided doses with close physician supervision 2
- For loss of effectiveness after months: Increase to 300 mg daily OR temporarily discontinue for several weeks then reinitiate 2
Concomitant Therapy Considerations
- Can be combined with levodopa or anticholinergic agents when either alone provides marginal benefit 2
- When added to levodopa, may smooth out fluctuations in improvement 2
Drug-Induced Extrapyramidal Reactions
- Standard dose: 100 mg twice daily (200 mg/day) 2
- Maximum for non-responders: 300 mg daily in divided doses 2
Critical Dosing Adjustments
Renal Impairment (Essential for All Indications)
Amantadine is 90% excreted unchanged in urine and accumulates dangerously in renal dysfunction. 3, 4
- CrCl 30-50 mL/min: 200 mg on day 1, then 100 mg daily 2
- CrCl 15-29 mL/min: 200 mg on day 1, then 100 mg every other day 2
- CrCl <15 mL/min: 200 mg every 7 days 2
- Hemodialysis patients: 200 mg every 7 days (hemodialysis removes <5% per session) 2, 3
- Half-life increases from 11.8 hours (normal) to 8.3 days in hemodialysis patients 3
Critical Safety Warnings
CNS Side Effects
- 5-10% of healthy adults experience nervousness, insomnia, impaired concentration, lightheadedness at 200 mg/day 1
- Elderly patients have higher risk of severe CNS effects, dizziness, and ataxia 1
- Dose reduction to ≤100 mg/day reduces CNS effects without compromising prophylactic efficacy 1
Resistance and Transmission
- Resistant strains emerge during treatment, especially after 5-7 days 1, 5
- Infected persons on amantadine must avoid contact with others during treatment and for 2 days after discontinuation, particularly with high-risk uninfected persons 1
- In nursing homes, cohort treated patients separately from those receiving prophylaxis 1
Contraindications and Monitoring
- Requires dose reduction in congestive heart failure, peripheral edema, orthostatic hypotension 2
- Monitor closely in patients with seizure disorders, neuropsychiatric conditions, or on psychotropic drugs 1
- Respiratory failure and ARDS are potential lethal complications of toxicity 4
Current Clinical Context
As of 2005-2006, high levels of adamantane resistance among circulating influenza A strains led to recommendations against using amantadine for influenza, though it remains appropriate for Parkinson's disease. 6