Memantine Dosing for Alzheimer's Disease
The recommended dose of memantine for moderate to severe Alzheimer's disease is 20 mg/day, achieved through gradual titration starting at 5 mg once daily and increasing by 5 mg increments weekly until reaching the target dose of 10 mg twice daily (20 mg total daily dose). 1
Standard Dosing Regimen
The FDA-approved titration schedule follows a structured 4-week approach 1:
- Week 1: 5 mg once daily
- Week 2: 10 mg/day (5 mg twice daily)
- Week 3: 15 mg/day (5 mg and 10 mg as separate doses)
- Week 4 and beyond: 20 mg/day (10 mg twice daily) - this is the target therapeutic dose 1
The minimum interval between dose increases is one week, and this 20 mg/day dosage has been shown to be effective in controlled clinical trials 1. This target dose demonstrated statistically significant improvements in cognition (measured by ADAS-cog and SIB scales), global function (CIBIC-plus), and quality of life measures across multiple trials 2.
Alternative Extended-Release Formulation
A once-daily extended-release formulation is available at 28 mg once daily, which may improve medication adherence by simplifying the dosing regimen 3. This formulation provides higher total daily exposure than the standard 20 mg/day IR formulation, though the two have not been directly compared in clinical trials 3. The ER capsules can be opened and sprinkled on applesauce for patients with swallowing difficulties 3.
Special Population Adjustments
Severe renal impairment requires dose reduction 1:
- Target dose: 5 mg twice daily (10 mg total daily) for patients with creatinine clearance 5-29 mL/min based on Cockcroft-Gault equation 1
Severe hepatic impairment warrants caution but no specific dose adjustment is mandated, though careful monitoring is advised 1.
Combination Therapy Considerations
When adding memantine to patients already on cholinesterase inhibitors (particularly donepezil), the same 20 mg/day target dose applies 4. A landmark trial demonstrated that memantine 20 mg/day added to stable donepezil therapy produced significant benefits in cognition (SIB), activities of daily living (ADCS-ADL19), and global outcomes (CIBIC-Plus) compared to donepezil alone 4. The American College of Physicians supports this combination approach, with the standard 20 mg/day memantine dose when combined with cholinesterase inhibitors 2, 5.
Critical Dosing Pitfalls to Avoid
Premature discontinuation: If a patient misses several days of memantine, do not resume at the full dose—restart at lower doses and retitrate using the standard weekly increments 1. This prevents adverse effects from abrupt reintroduction at higher doses.
Inadequate titration: Reaching the full 20 mg/day dose is essential for optimal therapeutic benefit unless side effects prevent further titration 5, 6. Studies demonstrating efficacy used this target dose 2.
Urinary alkalinization: Conditions that raise urine pH (severe urinary tract infections, renal tubular acidosis, strict vegetarian diets) decrease urinary elimination of memantine and can increase plasma levels, potentially requiring dose adjustment 1.
Tolerability Profile
Withdrawal rates due to adverse effects are relatively low at 7-12% (compared to 7-13% with placebo), with the most common side effects being headache, dizziness, diarrhea, and agitation 2, 6. Taking memantine with food does not affect absorption, so it can be administered with or without meals 1. The oral solution formulation should not be mixed with other liquids and requires use of the supplied dosing syringe 1.