Memantine Titration Protocol
Start memantine at 5 mg once daily and increase by 5 mg increments weekly until reaching the target dose of 20 mg daily (10 mg twice daily), with dose reductions required for severe renal impairment. 1
Standard Titration Schedule
The FDA-approved titration protocol follows a structured 4-week escalation 1:
- Week 1: 5 mg once daily 1
- Week 2: 10 mg daily (5 mg twice daily) 1
- Week 3: 15 mg daily (5 mg in morning, 10 mg in evening as separate doses) 1
- Week 4 and beyond: 20 mg daily (10 mg twice daily) - this is the target therapeutic dose 1
The minimum interval between dose increases must be one week to allow for adequate assessment of tolerability and therapeutic response 1. This weekly titration schedule has been validated in multiple clinical trials and represents the standard of care 2.
Administration Guidelines
- Memantine can be taken with or without food 1
- If a single dose is missed, do not double the next dose - simply resume the regular schedule 1
- If multiple days are missed, restart at lower doses and re-titrate from the beginning rather than resuming at the full dose 1
Special Population Adjustments
Severe Renal Impairment
For patients with creatinine clearance 5-29 mL/min, reduce the target dose to 5 mg twice daily (10 mg total daily) 1. The American Geriatrics Society case example demonstrates this principle, recommending dose reduction from 20 mg to 10 mg daily in a patient with estimated creatinine clearance of approximately 30 mL/min 3.
Severe Hepatic Impairment
Administer with caution in severe hepatic impairment, though specific dose adjustments are not definitively established 1.
Alternative Extended-Release Formulation
A 28 mg once-daily extended-release formulation is available, which provides higher total daily exposure than the standard 20 mg IR formulation 4. However, the immediate-release formulation with twice-daily dosing at 20 mg total remains the standard evidence-based regimen 1, 2.
Tolerability and Safety Monitoring
The gradual weekly titration minimizes adverse effects 2. Common side effects during titration include dizziness, headache, and confusion, but discontinuation rates due to adverse events are low (approximately 6.7% in long-term studies) 2. Once-daily dosing during titration has been shown to be well-tolerated with completion rates exceeding 90% 2.
The pharmacokinetic profile shows a long half-life of approximately 60-67 hours, supporting the gradual titration approach and explaining why steady-state is not achieved until after multiple doses 5.