Can amantadine be administered once daily?

Can Amantadine Be Given Once Daily?

Yes, amantadine can be administered once daily, but this is only appropriate for specific populations and formulations—standard immediate-release amantadine requires twice-daily dosing for most patients, while extended-release formulations are specifically designed for once-daily administration.

Standard Immediate-Release Formulation Dosing

Adults Under 65 Years

• Standard dosing is 100 mg twice daily (200 mg total daily dose) for both influenza prophylaxis/treatment and Parkinson's disease 1, 2
• The FDA label explicitly states that while 200 mg can be given as a single daily dose, if CNS side effects develop with once-daily dosing, a split dosage schedule (twice daily) may reduce such complaints 2
• Once-daily dosing at 200 mg has not been demonstrated to be as effective as the standard twice-daily regimen for all indications 2

Adults 65 Years and Older

• The total daily dose should be reduced to 100 mg per day due to age-related decline in renal function 1, 3, 4, 2
• This 100 mg can be given as a single daily dose in elderly patients 2
• The lower dose minimizes CNS side effects while maintaining efficacy 3

Pediatric Patients

• Children require twice-daily dosing 1, 2
• Ages 1-9 years: 5 mg/kg/day divided into two doses (maximum 150 mg/day) 1, 2
• Ages 10-12 years: 100 mg twice daily 1, 2

Extended-Release Formulations

ADS-5102 (Bedtime Dosing)

• ADS-5102 is specifically designed for once-daily administration at bedtime 5, 6
• This formulation provides high amantadine concentrations upon waking and throughout the day, with lower concentrations in the evening 5
• Peak concentration occurs 12-16 hours post-dose, resulting in mid-day peak levels when dyskinesia symptoms are most problematic 5
• Effective doses range from 260-340 mg once daily at bedtime for levodopa-induced dyskinesia 6

OS320 (Morning Dosing)

• OS320 extended-release tablets allow once-daily morning administration 7
• Peak amantadine concentration occurs approximately 7.5 hours post-dose 7
• At steady state, once-daily extended-release dosing is bioequivalent to twice-daily immediate-release dosing at the same total daily dose 7

Renal Impairment Adjustments

Dose reduction is mandatory for renal dysfunction, which may result in effective once-daily dosing:

• Creatinine clearance 30-50 mL/min/1.73m²: 200 mg on day 1, then 100 mg once daily 2
• Creatinine clearance 15-29 mL/min/1.73m²: 200 mg on day 1, then 100 mg every other day 2
• Creatinine clearance <15 mL/min/1.73m²: 200 mg every 7 days 2
• Hemodialysis patients: 200 mg every 7 days 2

Clinical Considerations

When Once-Daily Dosing May Be Appropriate

• Elderly patients (≥65 years) receiving the reduced 100 mg daily dose 1, 2
• Patients with renal impairment requiring dose reduction 2
• Patients using extended-release formulations specifically designed for once-daily administration 5, 7, 6
• Patients experiencing intolerance to 200 mg daily who require dose reduction to 100 mg 2

Important Caveats

• The 100 mg once-daily dose has not been studied for treatment of acute influenza illness and may not be as effective as 200 mg daily for prophylaxis 2
• If sleep disturbances occur with twice-daily dosing, avoid taking the second dose too close to bedtime rather than switching to once-daily dosing 3
• Standard immediate-release formulations given once daily at 200 mg may cause more CNS side effects than split dosing 2
• Extended-release and immediate-release formulations are not bioequivalent and cannot be substituted on a mg-per-mg basis 5