What is the recommended dosage of Memantine (N-methyl-D-aspartate receptor antagonist) for patients with Impaired renal function?

Memantine Dosage in Patients with Impaired Renal Function

For patients with severe renal impairment (creatinine clearance 5-29 mL/min), reduce memantine to 5 mg twice daily (10 mg total daily dose) instead of the standard 10 mg twice daily (20 mg total daily dose). 1

Standard Dosing in Normal Renal Function

• The recommended target dose for memantine in patients with normal renal function is 20 mg/day, administered as 10 mg twice daily 1
• Titration should begin at 5 mg once daily and increase in 5 mg increments weekly until reaching the target dose of 20 mg/day 1
• The minimum interval between dose increases is one week 1

Dose Adjustments for Renal Impairment

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

• No dosage adjustment is necessary - maintain the standard 10 mg twice daily regimen 2
• Pharmacokinetic studies show similar drug exposure compared to patients with normal renal function 2

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

• No dosage adjustment is necessary - maintain the standard 10 mg twice daily regimen 2
• Although drug exposure increases by approximately 60% compared to normal renal function, predicted steady-state concentrations remain within acceptable safety margins 2
• The FDA label supports continuing standard dosing in this population 1

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

• Reduce to 5 mg twice daily (10 mg total daily) 1, 2
• Drug exposure increases by approximately 115% at standard dosing, necessitating dose reduction 2
• This reduced regimen maintains steady-state plasma concentrations comparable to those achieved with standard dosing in patients with normal renal function 2
• An illustrative case from clinical practice demonstrates this principle: a patient with estimated creatinine clearance of approximately 30 mL/min had memantine reduced from 10 mg twice daily to 10 mg once daily 3

Practical Implementation

• Calculate creatinine clearance using the Cockcroft-Gault equation to determine appropriate dosing 1
• When initiating therapy in patients with severe renal impairment, start at 5 mg once daily and titrate to 5 mg twice daily over one week 1
• Memantine can be taken with or without food 1
• If doses are missed for several days, resume at lower doses and retitrate 1

Common Pitfalls to Avoid

• Do not use standard 20 mg/day dosing in severe renal impairment - this results in drug accumulation with plasma levels more than double those in patients with normal renal function 2
• Do not assume all renally impaired patients need dose reduction - only severe impairment (CrCl <30 mL/min) requires adjustment 1, 2
• Hemodialysis does not significantly contribute to memantine clearance, so timing relative to dialysis is not critical 1
• Monitor elderly patients carefully as renal function naturally declines with age, potentially requiring dose adjustment even without documented renal disease 3

Hepatic Impairment Considerations

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