What is the recommended dose of Amantadine (generic name) for various indications, including influenza A and Parkinson's disease, in patients with Impaired renal function (IRF)?

Amantadine Dosing in Patients with Impaired Renal Function

For patients with impaired renal function, amantadine requires dose reduction when creatinine clearance is ≤50 mL/min, with specific adjustments based on the degree of renal impairment as outlined in the package insert, and the daily dose should not exceed 100 mg in elderly patients (≥65 years) regardless of indication. 1

Dosing Algorithm Based on Renal Function

For Influenza A Treatment/Prophylaxis

Creatinine Clearance ≤50 mL/min:

• Dose reduction is mandatory and must follow package insert guidelines based on specific creatinine clearance values 1
• Close monitoring for adverse reactions is essential, as recommended dosages provide only approximations of optimal dosing 1
• Further dose reduction or discontinuation may be necessary if side effects emerge 1

Hemodialysis Patients:

• Hemodialysis contributes minimally (<5% per 4-hour session) to amantadine clearance 1, 2
• The elimination half-life extends dramatically to a mean of 8.3 days (range 7.0-10.3 days) in patients on chronic hemodialysis 2
• Standard hemodialysis does not effectively remove accumulated drug 1, 2

For Parkinson's Disease

Standard Dosing (Normal Renal Function):

• Initial dose: 100 mg once daily for patients with serious medical illnesses or those on high-dose antiparkinson drugs 3
• Maintenance dose: 100 mg twice daily (200 mg/day total) after one to several weeks if tolerated 3
• Maximum dose: Up to 400 mg daily in divided doses for select patients with suboptimal response, but requires close physician supervision 3

Renal Impairment Adjustments:

• The same creatinine clearance-based reductions apply as for influenza indications 1
• Extended-release formulations require dosing intervals of 24,48,72,96,120, or 168 hours depending on degree of renal impairment 4

Age-Specific Considerations

Elderly Patients (≥65 years):

• Maximum daily dose: 100 mg for both prophylaxis and treatment, regardless of indication 1
• Rationale: Renal function declines with age, increasing risk of drug accumulation 1
• Some elderly patients require further dose reduction below 100 mg daily 1
• Elderly women are at higher risk for side effects than elderly men at 100 mg daily due to smaller average body size 1

Pediatric Patients (1-9 years):

• Recommended dose: 5 mg/kg/day (not to exceed 150 mg/day) to reduce toxicity risk 1
• FDA-approved range is 4.4-8.8 mg/kg/day, but the lower end is preferred 1

Pediatric Patients (>10 years):

• Standard dose: 200 mg/day (100 mg twice daily) 1
• For children weighing <40 kg: Use 5 mg/kg/day regardless of age 1

Critical Safety Monitoring

High-Risk Populations Requiring Intensive Monitoring:

• Patients with creatinine clearance ≤50 mL/min 1
• Elderly patients, particularly those ≥65 years 1
• Patients with seizure disorders 1
• Patients with psychiatric disorders 1

Toxic Plasma Concentrations:

• Serious adverse reactions (myoclonus, hallucinations, delirium) occur when plasma concentrations exceed 3000 ng/mL 5
• Recommended therapeutic range: <3000 ng/mL, especially in elderly patients 5
• One case report documented a toxic level of 6200 ng/dL in a patient with end-stage renal disease prescribed normal dosing, resulting in ARDS 6

Pharmacokinetic Impact of Renal Impairment:

• Elimination half-life increases from 11.8 hours (normal function) to 18.5 hours to 33.8 days depending on severity of renal insufficiency 2
• Renal clearance decreases from 10,965 mL/h (normal) to 2,618 mL/h in severe renal impairment 4
• Amantadine is 90% excreted unchanged in urine via glomerular filtration and tubular secretion 1, 6

Common Pitfalls to Avoid

Failure to Adjust for Renal Function:

• This is the most critical error, leading to drug accumulation and severe toxicity 7, 8, 6
• Always calculate creatinine clearance before prescribing, particularly in elderly patients who may have normal serum creatinine despite reduced clearance 1, 7

Inadequate Monitoring After Dose Adjustment:

• Observe patients carefully after any dose reduction, as package insert guidelines provide only approximations 1
• Be prepared to further reduce dose or discontinue if adverse reactions emerge 1

Overlooking Drug Accumulation in Hemodialysis:

• Do not assume hemodialysis will clear accumulated amantadine—it removes <5% per session 1, 2
• Extended dosing intervals (up to weekly) may be necessary 4

Side Effect Profile and Management

Mild CNS Effects (5-14% incidence at 200 mg/day):

• Nervousness, anxiety, insomnia, difficulty concentrating, lightheadedness 1, 7, 8
• Often diminish after the first week despite continued use 1, 8
• Consider splitting daily dose if CNS effects develop with once-daily dosing 3

Severe CNS Effects:

• Marked behavioral changes, delirium, hallucinations, agitation, seizures 1, 7
• Associated with high plasma concentrations, particularly in patients with renal insufficiency taking 200 mg/day 1, 7
• Require immediate dose reduction or discontinuation 1, 7

Gastrointestinal Effects:

• Occur in approximately 3% of patients (vs. 1-2% with placebo) 1
• Nausea and anorexia are most common 1