How should amantadine (an antiviral and antiparkinsonian medication) dosage be decreased?

Decreasing Amantadine Dosage

Amantadine should never be discontinued abruptly due to the risk of parkinsonian crisis, neuroleptic malignant syndrome (NMS), and severe withdrawal symptoms including delirium, hallucinations, and agitation; instead, taper gradually while monitoring closely for deterioration. 1

Critical Safety Warning: Abrupt Discontinuation

• Abrupt withdrawal can precipitate parkinsonian crisis (sudden marked clinical deterioration), delirium, agitation, delusions, hallucinations, paranoid reactions, stupor, anxiety, depression, and slurred speech 1
• Sporadic cases of Neuroleptic Malignant Syndrome (NMS) have been reported with dose reduction or withdrawal, characterized by fever, muscle rigidity, altered consciousness, autonomic dysfunction, and elevated creatine phosphokinase 1
• Patients must be observed carefully during any dosage reduction, especially if receiving concurrent neuroleptics 1

Gradual Tapering Approach

When to Reduce Dose

Dose reduction is indicated in the following situations:

• Elderly patients (≥65 years): Maximum daily dose should not exceed 100 mg due to age-related decline in renal function 2, 3
• Renal impairment: Reduce dose when creatinine clearance is ≤50 mL/min/1.73m² 2
• Side effects: If patients experience CNS symptoms (nervousness, anxiety, insomnia, confusion, hallucinations), cardiovascular effects, or other adverse reactions 2, 4
• High plasma concentrations: Serious side effects (behavioral changes, delirium, hallucinations, seizures) are associated with high drug levels, particularly in patients with renal insufficiency, seizure disorders, or psychiatric conditions 2

Tapering Strategy

• Gradual dose reduction is essential - the FDA label explicitly warns against abrupt discontinuation 1
• For patients on 200 mg/day experiencing side effects, reduce to 100 mg/day initially 2
• Monitor carefully after each dose reduction for adverse reactions, and further reduce or discontinue if necessary 2
• If discontinuing completely, taper slowly over days to weeks rather than stopping suddenly 1

Special Population Considerations

Elderly Patients (≥65 years)

• Daily dose should not exceed 100 mg for either prophylaxis or treatment 2, 3
• Some elderly patients may require further dose reduction below 100 mg/day 2
• Elderly nursing home residents should receive only 100 mg/day of amantadine 2

Renal Impairment

• Creatinine clearance <50 mL/min/1.73m²: Consult package insert for specific dosing based on creatinine clearance 2
• Amantadine accumulates in plasma when renal function declines because it is primarily excreted unchanged in urine 1, 5
• Hemodialysis contributes minimally to drug clearance 2
• Observe patients carefully for adverse reactions and adjust dose accordingly 2

Patients with Seizure Disorders or Psychiatric Conditions

• These patients are at higher risk for serious CNS side effects with amantadine 2
• Lower doses and more gradual tapering may be necessary 2
• Close monitoring is essential during any dose adjustment 4

Monitoring During Dose Reduction

Watch for the following warning signs:

• Parkinsonian crisis: Sudden marked worsening of motor symptoms 1
• NMS symptoms: Fever, muscle rigidity, altered consciousness, autonomic instability 1
• Withdrawal symptoms: Delirium, agitation, hallucinations, confusion 1, 6
• Motor deterioration: Worsening tremor, rigidity, bradykinesia 6

Management of Withdrawal Symptoms

• If severe deterioration occurs during tapering, reintroduce amantadine immediately and stabilize the patient 6
• Consider slower tapering schedule or maintaining a lower maintenance dose rather than complete discontinuation 6
• Intensive symptomatic treatment and medical monitoring may be required if NMS develops 1

Common Pitfalls to Avoid

• Never stop amantadine abruptly - this is the most critical error and can lead to life-threatening complications 1
• Do not assume withdrawal effects mean the drug is still helping; withdrawal can occur even when therapeutic benefit has waned 7
• Do not reduce dose too quickly in elderly patients or those with renal impairment who have accumulated drug 2, 1
• Avoid dose reduction without considering concurrent neuroleptic use, which increases NMS risk 1