What is the maximum recommended dose of memantine (N-methyl-D-aspartate receptor antagonist) for patients with impaired renal function?

Maximum Dose of Memantine in Renal Impairment

For patients with severe renal impairment (creatinine clearance 5-29 mL/min), the maximum recommended dose of memantine is 5 mg twice daily (10 mg total daily dose), which is half the standard maximum dose used in patients with normal renal function. 1

Standard Dosing in Normal Renal Function

• The maximum recommended dose of memantine in patients with normal renal function is 20 mg/day, administered as 10 mg twice daily 1
• An extended-release formulation allows for 28 mg once daily dosing, though this is not the standard immediate-release regimen 2
• Dose titration should occur in 5 mg increments over at least one week intervals, starting from 5 mg once daily 1

Dose Adjustments for Renal Impairment

Severe Renal Impairment (CrCl 5-29 mL/min)

• Maximum dose: 5 mg twice daily (10 mg/day total) 1
• This represents a 50% dose reduction from the standard maximum dose 1
• Pharmacokinetic studies demonstrate that severe renal impairment increases memantine exposure (AUC) by 115% compared to normal renal function, necessitating dose reduction 3
• Simulations predict that 5 mg twice daily in severe renal impairment achieves steady-state concentrations (84 ng/mL) comparable to 10 mg twice daily in patients with normal renal function 3

Moderate Renal Impairment (CrCl 30-49 mL/min)

• No dose adjustment required - standard maximum of 20 mg/day (10 mg twice daily) can be used 1, 3
• Despite a 60% increase in AUC, predicted steady-state concentrations remain within acceptable ranges 3

Mild Renal Impairment (CrCl 50-80 mL/min)

• No dose adjustment required - standard maximum of 20 mg/day (10 mg twice daily) 1, 3
• Pharmacokinetic parameters are similar to those with normal renal function 3

Clinical Rationale for Dose Reduction

The dose reduction in severe renal impairment is based on memantine's elimination profile:

• Approximately 48% of memantine is excreted unchanged in urine via active tubular secretion 1
• Terminal elimination half-life increases by 95% in severe renal impairment compared to normal function 1, 3
• Renal clearance involves pH-dependent tubular reabsorption, making it particularly sensitive to renal function 1

Important Considerations

• Elderly patients warrant careful monitoring as renal function naturally declines with age, potentially requiring dose adjustment even without documented severe renal disease 4
• Conditions that raise urine pH (such as renal tubular acidosis or severe urinary tract infections) may further decrease urinary elimination of memantine, potentially increasing plasma levels 1
• The dose reduction recommendation is based on creatinine clearance calculated using the Cockcroft-Gault equation 1

Common Pitfalls to Avoid

• Do not use standard 20 mg/day dosing in severe renal impairment - this doubles the appropriate exposure and increases risk of adverse effects 1, 3
• Do not assume elderly patients have normal renal function - calculate creatinine clearance rather than relying on serum creatinine alone, as age-related decline may not be reflected in serum values 4
• Monitor for drug interactions with other renally eliminated cationic drugs (hydrochlorothiazide, metformin, cimetidine) that may compete for tubular secretion and alter memantine levels 1