What is the typical dosing regimen for Amantadine (Amantadine) in the treatment of Parkinson's disease?

Amantadine Dosing in Parkinson's Disease

For Parkinson's disease, start amantadine at 100 mg once daily in patients with serious medical illnesses or those on high-dose antiparkinson drugs, then increase to 100 mg twice daily (200 mg/day total) after 1-2 weeks if needed; patients may require up to 300-400 mg/day in divided doses for optimal benefit, though doses above 200 mg/day require close physician supervision. 1

Standard Adult Dosing

• The typical maintenance dose is 100 mg twice daily (200 mg/day total) when used as monotherapy for Parkinson's disease 1
• Onset of action occurs within 48 hours of initiation 1
• For patients requiring higher doses, increase to 300 mg/day in divided doses if response at 200 mg/day is suboptimal 1, 2
• Some patients may benefit from doses up to 400 mg/day in divided doses, but this requires close physician supervision 1

Initiation Strategy

• Begin with 100 mg once daily in patients with serious associated medical illnesses or those receiving high doses of other antiparkinson drugs 1
• After 1-7 weeks at 100 mg daily, increase to 100 mg twice daily if necessary 1
• This conservative approach minimizes CNS side effects while establishing tolerability 1

Elderly Patients (≥65 Years)

• Reduce the daily dose to 100 mg total (50 mg twice daily or 100 mg once daily) in patients 65 years and older 3
• This reduction accounts for age-related decline in renal function and reduces CNS side effects 3
• Elderly women are at higher risk for side effects due to smaller average body size 4

Renal Impairment Adjustments

Dosing must be adjusted based on creatinine clearance: 1

• CrCl 30-50 mL/min/1.73m²: 200 mg on day 1, then 100 mg daily thereafter 1
• CrCl 15-29 mL/min/1.73m²: 200 mg on day 1, then 100 mg every other day 1
• CrCl <15 mL/min/1.73m²: 200 mg every 7 days 1
• Hemodialysis patients: 200 mg every 7 days 1

The drug package insert should be consulted for creatinine clearance <50 mL/min/1.73m² 4, 3. Plasma amantadine concentrations increase significantly with renal dysfunction, and levels exceeding 3000 ng/mL are associated with myoclonus, hallucinations, and delirium 5.

Concomitant Therapy Considerations

With Levodopa

• When initiating amantadine and levodopa concurrently, hold amantadine constant at 100 mg once or twice daily while gradually increasing levodopa to optimal benefit 1
• When adding amantadine to optimized levodopa therapy, additional benefit may occur, including smoothing out fluctuations in improvement 1

With Anticholinergic Drugs

• Patients not responding to anticholinergic antiparkinson drugs alone may respond to amantadine 1
• Concomitant use may produce additional benefit when each drug provides only marginal benefit alone 1

Managing Loss of Efficacy

Patients commonly experience a fall-off in effectiveness after several months: 1

• Option 1: Increase dose to 300 mg/day in divided doses 1
• Option 2: Temporarily discontinue amantadine for several weeks, then reinitiate—this may restore benefit in some patients 1
• Option 3: Consider adding other antiparkinson drugs 1

Research confirms that 27% of patients stop amantadine within 2 years, often due to loss of efficacy or adverse effects 6.

Primary Indication in Parkinson's Disease

• Amantadine prescription is strongly correlated with the presence of levodopa-induced dyskinesias (OR 7.02) 6
• The drug is typically initiated after a median of 7 years from PD diagnosis 6
• A 38% reduction in dyskinesias has been demonstrated at 300 mg/day 2
• Limited evidence suggests benefit for freezing of gait, with 10 of 11 patients reporting improvement at 100 mg twice daily, though benefit may be transient after 4 months 7

Critical Safety Considerations

CNS Side Effects

• Monitor for nervousness, anxiety, insomnia, difficulty concentrating, and lightheadedness 3
• If sleep disturbances occur, avoid taking the second dose too close to bedtime 3
• Patients with seizure disorders should be observed closely for increased seizure activity 4

Withdrawal Precautions

• Never abruptly discontinue amantadine—severe hyperthermia (39-40°C) can occur 2
• If withdrawal symptoms develop, return to the previous tolerated dose and wait 1-2 weeks for stabilization before resuming a slower taper 3
• Taper over at least 15 days when discontinuing 2

Plasma Concentration Monitoring

• Keep plasma concentrations below 3000 ng/mL to avoid myoclonus, hallucinations, and delirium, particularly in elderly patients 5
• Measure plasma levels 3 hours after morning dose if toxicity is suspected 5

Common Pitfalls to Avoid

• Failing to reduce dose in elderly patients (≥65 years): This population requires 100 mg/day maximum due to age-related renal decline 3
• Not adjusting for renal impairment: Amantadine accumulates significantly with CrCl ≤50 mL/min/1.73m², requiring dose reduction 3, 1
• Abrupt discontinuation: Always taper to avoid severe hyperthermia and withdrawal symptoms 2
• Ignoring loss of efficacy: Consider dose increase, drug holiday, or alternative therapies when benefit diminishes 1