Dose Adjustments for Renal Impairment (CrCl 25 mL/min)
With a creatinine clearance of 25 mL/min, you must reduce memantine to 10 mg once daily, while donepezil, brexpiprazole, and valproic acid can remain at their current doses without adjustment.
Memantine - REQUIRES DOSE REDUCTION
- Memantine must be reduced from 20 mg to 10 mg once daily in patients with severe renal impairment (CrCl 5-29 mL/min). 1, 2
- The drug is primarily renally eliminated, and failure to adjust dosing leads to excessive accumulation and increased risk of toxicity including confusion, dizziness, and hallucinations. 1, 3
- This represents a 50% dose reduction from the current regimen, which is standard practice for renally cleared medications in severe renal dysfunction. 1
Donepezil - NO ADJUSTMENT NEEDED
- Donepezil does not require dose adjustment in renal impairment because it undergoes hepatic metabolism via CYP2D6 and CYP3A4 rather than renal elimination. 4
- The current dose of 10 mg once daily can be continued safely. 1
Brexpiprazole - NO ADJUSTMENT NEEDED
- Brexpiprazole is metabolized hepatically by CYP2D6 and CYP3A4, not renally excreted. 4
- While dose adjustments are required for drug interactions or hepatic impairment, renal dysfunction does not necessitate dose modification. 4
- The current dose of 0.5 mg once daily can be maintained. 4
Valproic Acid - NO ADJUSTMENT NEEDED
- Valproic acid is primarily metabolized by the liver with minimal renal excretion of unchanged drug. 1
- The current dose of 500 mg once daily does not require adjustment based solely on renal function. 1, 3
- However, monitor for increased unbound (free) drug levels if hypoalbuminemia is present, as this is common in renal disease and can increase toxicity risk. 1, 3
Critical Monitoring Considerations
- Verify the creatinine clearance calculation using the Cockcroft-Gault equation rather than relying on serum creatinine alone, especially in elderly patients with reduced muscle mass who may have falsely reassuring creatinine values. 5, 2
- Monitor closely for signs of memantine toxicity after dose reduction, including confusion, agitation, dizziness, and hallucinations. 1
- Watch for increased adverse effects from all medications due to potential alterations in protein binding and volume of distribution that occur in renal disease. 1, 3
- The combination of antipsychotic (brexpiprazole) with dementia medications carries increased mortality risk in elderly patients with dementia, regardless of renal function. 4