Amantadine Dosing Recommendations
For Gocovri (extended-release amantadine) in adults with Parkinson's disease and dyskinesia, start with 137 mg once daily at bedtime for one week, then increase to the target dose of 274 mg once daily at bedtime. 1
Standard Dosing for Gocovri (Extended-Release)
The FDA-approved Gocovri formulation provides a delayed-release/extended-release profile designed for bedtime administration, achieving high plasma concentrations throughout the day when dyskinesia is most problematic 2. This formulation is specifically approved for levodopa-induced dyskinesia in Parkinson's disease.
- Initial dose: 137 mg once daily at bedtime for 1 week
- Target dose: 274 mg once daily at bedtime
- Timing: Must be taken at bedtime to optimize daytime drug levels 1
Renal Impairment Dose Adjustments
Gocovri requires substantial dose reduction in renal impairment because amantadine is primarily eliminated by the kidneys 1:
Moderate Renal Impairment (CrCl 30-59 mL/min/1.73 m²)
- Initial dose: 68.5 mg once daily at bedtime for 1 week
- Maximum dose: 137 mg once daily at bedtime (50% dose reduction) 1
Severe Renal Impairment (CrCl 15-29 mL/min/1.73 m²)
- Dose: 68.5 mg once daily at bedtime (both initial and maximum dose) 1
End-Stage Renal Disease (CrCl <15 mL/min/1.73 m²)
- Contraindicated - do not use Gocovri 1
Important caveat: Creatinine clearance should be estimated using the MDRD method 1. Hemodialysis contributes minimally to amantadine clearance, so supplemental dosing post-dialysis is not beneficial 3.
Immediate-Release Amantadine Dosing
For immediate-release formulations (used for influenza or off-label Parkinson's disease treatment), dosing differs significantly:
Standard Adult Dosing
- Typical dose: 100 mg twice daily or 200 mg once daily 3
Elderly Patients (>65 years)
- Maximum dose: 100 mg daily (not to exceed) due to age-related decline in renal function 3
- Rationale: Even with normal creatinine, elderly patients have reduced renal clearance and higher risk of CNS adverse effects
Renal Impairment (Immediate-Release)
- CrCl <50 mL/min/1.73 m²: Dose reduction required; consult package insert for specific creatinine clearance-based dosing 3
- CrCl <10 mL/min: Reduce to 100 mg daily 3
Critical Safety Considerations
Monitor elderly patients closely regardless of formulation - they experience higher rates of hallucinations and falls, particularly those ≥65 years 1. While no age-based dose adjustment is required for Gocovri, renal function monitoring is essential since elderly patients are more likely to have decreased renal function 1.
The extended-release and immediate-release formulations are NOT interchangeable - they have different pharmacokinetic profiles and are not bioequivalent 2. Gocovri achieves 1.4- to 2.0-fold higher daytime plasma concentrations compared to immediate-release formulations 2.
Common adverse events with Gocovri include hallucinations, dizziness, dry mouth, and peripheral edema, occurring in >15% of patients 4. These are typically transient and mild-to-moderate in severity.