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), as specified by FDA labeling. 1
Standard Titration Schedule
The FDA-approved titration follows a structured 4-week escalation:
- Week 1: 5 mg once daily 1
- Week 2: 10 mg daily (5 mg twice daily) 1
- Week 3: 15 mg daily (5 mg morning, 10 mg evening as separate doses) 1
- Week 4 onward: 20 mg daily (10 mg twice daily) - this is the therapeutic target dose 1
The minimum interval between dose increases must be one week to allow adequate assessment of tolerability and minimize adverse effects such as dizziness, confusion, and headache. 1
Formulation Considerations
Immediate-Release (IR) Formulation
- Administered twice daily at target dose of 20 mg/day total 1
- Available as tablets or oral solution (2 mg/mL) 1
- Oral solution should not be mixed with other liquids and requires the supplied dosing syringe 1
Extended-Release (ER) Formulation
- Single daily dose of 28 mg once daily 2
- Provides higher total daily exposure than IR formulation 2
- Capsules can be opened and sprinkled on applesauce for patients with swallowing difficulties 2
- May improve adherence due to once-daily dosing 2
Special Population Adjustments
Severe Renal Impairment
Reduce the target dose to 10 mg daily (5 mg twice daily) in patients with creatinine clearance 5-29 mL/min. 3, 1 This adjustment is critical as memantine is primarily renally eliminated, and accumulation can occur with impaired kidney function. 1
Severe Hepatic Impairment
Administer with caution in severe hepatic impairment, though no specific dose adjustment is mandated by FDA labeling. 1
Conditions Raising Urine pH
Exercise caution in patients with conditions that alkalinize urine (e.g., renal tubular acidosis, severe urinary tract infections), as this decreases urinary elimination and increases plasma memantine levels. 1
Dosing Interruptions
If a patient misses a single dose, do not double the next dose—simply resume the regular schedule. 1
If memantine is discontinued for several days, restart at lower doses and retitrate upward using the standard weekly escalation protocol to minimize the risk of adverse effects upon reintroduction. 1
Administration Guidelines
- Memantine can be taken with or without food 1
- For oral solution: use only the supplied dosing device and slowly squirt into the corner of the patient's mouth 1
- The most common adverse reactions during titration include dizziness, headache, confusion, and constipation (each occurring in ≥5% of patients) 1
Clinical Monitoring
Monitor for tolerability during each weekly dose escalation, particularly watching for:
- Dizziness and falls 1
- Confusion or worsening cognition 1
- Headache 1
- Gastrointestinal symptoms (constipation, diarrhea) 1
The 20 mg/day dose has been demonstrated effective in controlled trials for moderate to severe Alzheimer's disease. 1 Long-term safety data support memantine use for at least one year with good tolerability. 4