Amantadine: Uses and Dosing
Primary Indications
Amantadine is indicated for prophylaxis and treatment of influenza A virus infections and for management of Parkinson's disease and drug-induced extrapyramidal reactions. 1
Influenza A: Treatment and Prophylaxis
Treatment Dosing
For treatment of acute influenza A, amantadine should be started within 24-48 hours of symptom onset and continued for 24-48 hours after symptoms resolve (typically 3-5 days total). 2
Adults (13-64 years)
- Standard dose: 200 mg daily (100 mg twice daily) 2
- Alternative: 200 mg as single daily dose; if CNS side effects develop, split to 100 mg twice daily 1
- Patients ≥65 years: Maximum 100 mg daily due to age-related renal decline 2, 3
Pediatric Patients
- Ages 1-9 years: 5 mg/kg/day (maximum 150 mg/day) in two divided doses 2, 3
- Ages 10-12 years: 100 mg twice daily 2
- Children <40 kg (88 lb): 5 mg/kg/day regardless of age 2
- Use in children <1 year has not been adequately evaluated 2
Prophylaxis Dosing
Prophylaxis is 70-90% effective in preventing influenza A illness when taken daily throughout the period of viral activity in the community. 2
- Same dosing as treatment for all age groups 2
- Start prophylaxis in anticipation of outbreak or immediately after known exposure 1
- Continue for at least 10 days following known exposure 1
- When used with inactivated influenza vaccine, continue for 2-4 weeks after vaccination until protective antibodies develop 2, 1
- When vaccine is unavailable or contraindicated, continue for duration of influenza A activity in community 1
Critical Limitations for Influenza Use
- Amantadine is only effective against influenza A, not influenza B 2
- No evidence that amantadine prevents serious influenza-related complications 2
- Resistance emerges in approximately 30% of treated patients within 2-3 days of therapy 4, 5
- Infected persons on amantadine should avoid contact with others during treatment and for 2 days after discontinuation to prevent transmission of resistant strains 2
Parkinson's Disease and Drug-Induced Extrapyramidal Reactions
Parkinson's Disease Dosing
Initial dose: 100 mg once daily for patients with serious medical illnesses or those on high-dose antiparkinson drugs; after 1-several weeks, increase to 100 mg twice daily if necessary. 1
- Standard maintenance: 100 mg twice daily (200 mg/day) 1
- Onset of action typically within 48 hours 1
- Some patients may benefit from doses up to 400 mg daily in divided doses, but require close physician supervision 1
- Loss of effectiveness after several months is common; benefit may be regained by increasing to 300 mg daily or temporarily discontinuing for several weeks then reinitiating 1
Drug-Induced Extrapyramidal Reactions
- Standard dose: 100 mg twice daily (200 mg/day) 1
- May increase to 300 mg daily in divided doses for suboptimal responders 1
Concomitant Therapy Considerations
- Can be combined with anticholinergic antiparkinson drugs for additive benefit 1
- When combined with levodopa, hold amantadine constant at 100 mg once or twice daily while titrating levodopa 1
- May smooth out fluctuations in patients on levodopa alone 1
Renal Impairment Dosing
Dose reduction is mandatory for creatinine clearance ≤50 mL/min/1.73m² because amantadine is 90% excreted unchanged in urine. 3, 1, 6
Specific Adjustments
| Creatinine Clearance | Dosing Regimen |
|---|---|
| 30-50 mL/min | 200 mg on day 1, then 100 mg daily [1] |
| 15-29 mL/min | 200 mg on day 1, then 100 mg every other day [1] |
| <15 mL/min | 200 mg every 7 days [1] |
| Hemodialysis | 200 mg every 7 days [1] |
- Hemodialysis removes <5% of amantadine per 4-hour session; half-life during chronic hemodialysis averages 8.3 days (range 7.0-10.3 days) 6
- Close monitoring for adverse reactions is essential as recommended dosages provide only approximations 2, 3
Elderly Patients (≥65 Years)
Maximum daily dose: 100 mg regardless of indication due to age-related decline in renal function. 2, 3, 1
- Elderly women are at higher risk for side effects than elderly men at 100 mg daily due to smaller average body size 3
- CNS side effects (dizziness, ataxia, confusion) occur more frequently and severely in elderly patients 2
- For nursing home residents on rimantadine, dose should not exceed 100 mg daily 2
Side Effects and Safety Monitoring
Common CNS Side Effects (5-14% at 200 mg/day)
- Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness 2, 3
- Gastrointestinal effects: anorexia, nausea 2
- Side effects typically diminish after the first week or upon discontinuation 2
Severe CNS Effects (Associated with High Plasma Concentrations)
- Marked behavioral changes, delirium, hallucinations, agitation, seizures 3
- Particularly in elderly patients, those with renal disease, seizure disorders, or altered mental status 2, 3
- One case report describes acute respiratory distress syndrome (ARDS) in a patient with ESRD prescribed 300 mg/day with serum level of 6200 ng/dL (normal 700-1000 ng/dL) 7
High-Risk Populations Requiring Intensive Monitoring
- Creatinine clearance ≤50 mL/min 2, 3
- Age ≥65 years 2, 3
- Seizure disorders or psychiatric conditions 2, 3
- Congestive heart failure, peripheral edema, orthostatic hypotension 1
Critical Clinical Pitfalls
Dosing Errors in Renal Impairment
The most dangerous error is prescribing standard doses (200 mg/day) to patients with renal insufficiency, leading to severe toxicity including potential ARDS. 7 Always calculate creatinine clearance and adjust accordingly 3, 1.
Resistance Development
Discontinue amantadine as soon as clinically warranted (usually 3-5 days) to minimize emergence of resistant strains. 2 Do not use for prolonged treatment courses 2.
Loss of Efficacy in Parkinson's Disease
Anticipate loss of effectiveness after several months; have a plan to either increase dose to 300 mg daily, temporarily discontinue for several weeks, or add other antiparkinson agents 1.
Sleep Disturbances
If insomnia occurs, avoid taking the second dose too close to bedtime or switch from twice-daily to once-daily dosing 8, 1.