Is there an association between Memantine (Namenda) and Chronic Kidney Disease (CKD)?

From the Guidelines

Memantine should be used with caution in patients with chronic kidney disease (CKD) due to its potential to accumulate in the body and increase the risk of side effects. The evidence from high-quality studies, such as those evaluating memantine in patients with Alzheimer's disease and vascular dementia 1, suggests that memantine can be effective in improving cognition and behavior in patients with dementia. However, the studies did not specifically address the use of memantine in patients with CKD.

When considering the use of memantine in patients with CKD, it is essential to take into account the patient's kidney function and adjust the dose accordingly. For patients with mild CKD (GFR 50-80 mL/min), the standard dose of 10 mg twice daily can typically be used. For moderate CKD (GFR 30-49 mL/min), the dose should be reduced to 5 mg twice daily. In severe CKD (GFR 5-29 mL/min), the maximum recommended dose is 5 mg once daily.

Key considerations when using memantine in patients with CKD include:

• Regular monitoring of kidney function to ensure that the dose is appropriate and to minimize the risk of side effects
• Close monitoring for signs of memantine toxicity, such as dizziness, headache, confusion, and hallucinations
• Adjusting the dose as needed if kidney function worsens or if side effects occur
• Consulting with a healthcare provider before starting or adjusting memantine dosing in the context of kidney disease.

Overall, the use of memantine in patients with CKD requires careful consideration of the potential benefits and risks, as well as regular monitoring to ensure safe and effective use.

From the FDA Drug Label

Memantine pharmacokinetics were evaluated following single oral administration of 20 mg memantine HCl in 8 subjects with mild renal impairment (creatinine clearance, CLcr, >50 to 80 mL/min), 8 subjects with moderate renal impairment (CLcr 30 to 49 mL/min), 7 subjects with severe renal impairment (CLcr 5 to 29 mL/min) and 8 healthy subjects (CLcr > 80 mL/min) matched as closely as possible by age, weight and gender to the subjects with renal impairment. Mean AUC0-∞ increased by 4%, 60%, and 115% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects. The terminal elimination half-life increased by 18%, 41%, and 95% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects No dosage adjustment is recommended for patients with mild and moderate renal impairment. Dosage should be reduced in patients with severe renal impairment [see Dosage and Administration (2)]

Memantine and Chronic Kidney Disease:

• Key Points:
  • Memantine is predominantly renally eliminated.
  • Dosage adjustment is needed in patients with severe renal impairment.
  • No dosage adjustment is recommended for patients with mild or moderate renal impairment.
• Clinical Decision: Patients with chronic kidney disease should be monitored closely, and dosage adjustments should be made according to the severity of renal impairment. 2

From the Research

Mementanine and Chronic Kidney Disease

• The effect of renal impairment on the pharmacokinetics of memantine was studied in Japanese subjects with different levels of renal function 3.
• The results showed that exposure to memantine was higher in subjects with mild, moderate, and severe renal impairment compared to those with normal renal function.
• The study suggested that the dose of memantine should be halved in patients with renal impairment 3.
• Another study found that there is a lack of consistency in dosing information for drugs, including memantine, in patients with renal impairment 4.
• The study highlighted the need for an evidence-based approach to drug dosage adjustment in patients with chronic kidney disease 4.

Dosing Adjustments for Mementanine in Chronic Kidney Disease

• A study on the use of newer anticoagulants in patients with chronic kidney disease found that dosing adjustments are necessary for patients with severe renal impairment 5.
• The study suggested that unfractionated heparin is the preferred anticoagulant for use in most patients with severe renal impairment 5.
• Another study emphasized the importance of conducting full pharmacokinetic studies for drugs that are likely to be administered to patients with kidney disease, including those that are not excreted by the kidney 6.
• The study recommended that information on dosing adjustments for impaired kidney function should be clearly stated in the package insert of the drugs 6.

Association between Cholinesterase Inhibitors and Kidney Function Decline

• A recent study found that the use of cholinesterase inhibitors, including memantine, was associated with a lower risk of chronic kidney disease progression and death in patients with Alzheimer's dementia 7.
• The study suggested that the activation of the cholinergic anti-inflammatory pathway may have beneficial effects on the kidney 7.
• However, the study did not specifically investigate the effect of memantine on kidney function decline in patients with chronic kidney disease 7.