What is the recommended dosage of memantine?

Memantine Dosing for Alzheimer's Disease

The recommended dosage of memantine for moderate to severe Alzheimer's disease is 20 mg/day (10 mg twice daily) for the immediate-release formulation, or 28 mg once daily for the extended-release formulation, with dose reductions required for severe renal impairment. 1

Standard Dosing Regimen

Immediate-Release Formulation

Memantine should be initiated at 5 mg once daily and titrated upward in 5 mg increments at weekly intervals to the target dose of 20 mg/day (10 mg twice daily). 1 The specific titration schedule is:

• Week 1: 5 mg once daily 1
• Week 2: 10 mg/day (5 mg twice daily) 1
• Week 3: 15 mg/day (5 mg and 10 mg as separate doses) 1
• Week 4 and beyond: 20 mg/day (10 mg twice daily) 1

The 20 mg/day dose has been shown to be effective in controlled clinical trials for moderate to severe Alzheimer's disease. 1, 2

Extended-Release Formulation

Memantine ER 28 mg once daily is an alternative formulation that may improve medication adherence through simplified dosing. 3 This formulation provides higher total daily exposure compared to the immediate-release 20 mg/day regimen, though the clinical implications of this difference remain unclear as direct comparative trials have not been conducted. 3

Dose Adjustments for Renal Impairment

For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the target dose should be reduced to 5 mg twice daily (10 mg/day total). 1 This is critical because memantine is primarily eliminated renally, and accumulation can occur with declining kidney function. 4

• Mild to moderate renal impairment: No dose adjustment required 1
• Severe renal impairment (CrCl 5-29 mL/min): Reduce to 5 mg twice daily 1
• Elderly patients: Monitor carefully as renal function naturally declines with age, potentially requiring dose adjustment even without documented renal disease 4

Hepatic Impairment

Memantine should be administered with caution to patients with severe hepatic impairment, though specific dose adjustments are not provided. 1

Combination Therapy

Memantine can be safely combined with cholinesterase inhibitors (such as donepezil) in patients with moderate to severe Alzheimer's disease. 2 A landmark randomized controlled trial demonstrated that adding memantine 20 mg/day to stable donepezil therapy resulted in significantly better outcomes on cognition (SIB), activities of daily living (ADCS-ADL19), and global function (CIBIC-Plus) compared to donepezil alone (all P≤0.03). 2

Administration Considerations

• Memantine can be taken with or without food 1
• If a single dose is missed, do not double the next dose 1
• If multiple doses are missed, resume at lower doses and retitrate upward 1
• For patients with swallowing difficulties, the extended-release capsules can be opened and sprinkled on applesauce 3

Common Pitfalls to Avoid

• Do not use standard 20 mg/day dosing in patients with severe renal impairment (CrCl <30 mL/min), as this increases risk of adverse effects due to drug accumulation 1
• Do not escalate doses faster than weekly intervals, as this may increase the risk of adverse events 1
• Conditions that raise urine pH (such as renal tubular acidosis or severe urinary tract infections) can decrease urinary elimination of memantine, resulting in increased plasma levels 1