Amantadine Administration Timing
Do not administer standard immediate-release amantadine at bedtime due to the high risk of insomnia and CNS stimulation; however, the extended-release formulation (ADS-5102/GOCOVRI) is specifically designed for bedtime dosing.
Immediate-Release Amantadine: Avoid Bedtime Dosing
- Standard immediate-release amantadine should NOT be given at bedtime because insomnia is one of the most common CNS side effects, occurring in approximately 5-10% of patients 1
- The ACIP guidelines specifically recommend avoiding taking the second dose too close to bedtime if sleep disturbances occur 2
- Common CNS side effects that would be problematic at bedtime include nervousness, anxiety, insomnia, difficulty concentrating, and lightheadedness 1
- For immediate-release formulations, the standard dosing is divided into two doses during the day (e.g., 100 mg twice daily for adults), not at bedtime 1
Extended-Release Amantadine: Specifically Designed for Bedtime
- Extended-release amantadine (ADS-5102) at 274 mg is FDA-approved for once-daily administration at bedtime for treatment of levodopa-induced dyskinesia in Parkinson's disease 3
- This formulation is engineered to provide a slow initial rise in plasma concentration with delayed time to peak (12-16 hours), resulting in high concentrations upon waking and throughout the day when dyskinesia is most problematic 4
- Bedtime dosing of extended-release amantadine achieves 1.4- to 2.0-fold higher plasma concentrations during daytime hours compared to immediate-release formulations, while maintaining lower concentrations in the evening 4
- Clinical trials demonstrated that once-daily bedtime dosing of extended-release amantadine (274 mg) significantly reduced dyskinesia by 27% and increased ON time without troublesome dyskinesia 5
Clinical Algorithm for Timing Decision
If prescribing immediate-release amantadine:
- Administer in divided doses during waking hours (typically morning and early afternoon) 1
- For elderly patients (≥65 years), use 100 mg total daily dose, which can be given as 50 mg twice daily during the day 2
- Avoid late afternoon or evening dosing to minimize insomnia risk 2
If prescribing extended-release amantadine:
- Administer 274 mg once daily at bedtime 3, 4
- This is the only amantadine formulation appropriate for bedtime administration 3
Common Pitfall to Avoid
The critical error is confusing immediate-release and extended-release formulations—never give immediate-release amantadine at bedtime, as this will likely cause insomnia and other CNS stimulation effects that interfere with sleep 1, 2. Only the extended-release formulation is designed for bedtime dosing 3, 4.