From the Guidelines
Amantadine is not effectively dialyzable in patients with impaired renal function.
Key Points
- A reduction in dosage is recommended for patients with creatinine clearance <50 mL/min/1.73m2 1.
- Hemodialysis contributes minimally to amantadine clearance, as stated in multiple studies 1.
- Amantadine is excreted unchanged in the urine by glomerular filtration and tubular secretion, and its renal clearance is reduced substantially in persons with renal insufficiency 1.
- Guidelines for amantadine dosage based on creatinine clearance are found in the package insert, but patients should be observed carefully for adverse reactions 1.
Clinical Implications
- Patients with impaired renal function should be closely monitored for adverse reactions when taking amantadine.
- Dosage adjustments may be necessary to prevent adverse effects in patients with creatinine clearance <50 mL/min/1.73m2.
- Hemodialysis is not an effective method for removing amantadine from the body, and alternative treatment strategies may be necessary in patients with severe renal impairment.
From the FDA Drug Label
Amantadine hydrochloride is removed in negligible amounts by hemodialysis. The elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 mL/min/1. 73 m and averages eight days in patients on chronic maintenance hemodialysis.
- Amantadine is not significantly dialyzable in patients with impaired renal function, as it is removed in negligible amounts by hemodialysis 2.
- The elimination half-life is increased in patients with renal insufficiency, indicating that the drug accumulates in the body when renal function declines 2.
From the Research
Amantadine Dialyzability in Patients with Impaired Renal Function
- Amantadine is poorly dialyzable in patients with impaired renal function, with less than 5% of the dose removed by each 4-hour hemodialysis 3.
- The amount of amantadine removed by dialysis is small, and frequently repeated dialysis may be required to remove the drug 4, 5.
- Amantadine has a large volume of distribution and is poorly excreted in patients on hemodialysis, with a mean half-life of 24.3 hours in patients receiving maintenance hemodialysis 5.
- Renal impairment is associated with reduced amantadine clearance, and dose regimens may need to be adjusted to provide systemic amantadine exposure similar to patients with normal renal function 6.
- Amantadine tends to accumulate in patients with impaired renal function, and high serum concentrations can lead to toxicity, including neurological manifestations and respiratory failure 7.