Can memantine cause urinary frequency?

Memantine and Urinary Frequency

Yes, memantine can cause urinary frequency as a side effect, though it is not among the most commonly reported adverse effects of the medication.

Mechanism and Evidence

Memantine is an NMDA receptor antagonist primarily used in the treatment of moderate to severe Alzheimer's disease. While the guidelines and research don't specifically highlight urinary frequency as a primary side effect of memantine, there are several important considerations:

1. Pharmacokinetics and Renal Excretion:

   • Memantine is primarily cleared through the kidneys 1, 2, 3
   • The renal excretion of memantine is significantly affected by urine pH, with 7-10 fold higher clearance in acidic urine compared to alkaline urine 1
   • This high renal clearance could potentially affect urinary patterns in some patients

2. Documented Side Effects:

   • The most commonly reported side effects of memantine include constipation, dizziness, headache, and confusion 4
   • While urinary frequency is not specifically highlighted in the main side effect profile, medications with high renal clearance can sometimes affect urinary patterns

3. Special Populations:

   • Patients with renal impairment have significantly altered memantine pharmacokinetics 2, 3
   • In patients with severe renal impairment, memantine exposure can be 2.33 times higher than in those with normal renal function 3
   • This increased exposure could potentially lead to greater urinary side effects

Clinical Implications

Dosing Considerations

• For patients with normal to moderate renal function, standard dosing (10 mg twice daily) is appropriate 2
• For patients with severe renal impairment (CrCl 5-29 mL/min), a reduced dose of 5 mg twice daily is recommended 2, 3

Monitoring and Management

If a patient reports urinary frequency while taking memantine:

1. Rule out other causes:

   • Urinary tract infection (UTI) should be excluded 5
   • Consider other medications that might contribute to urinary symptoms

2. Consider drug interactions:

   • Medications that utilize the organic cation transporter-2 in the renal tubule (such as trimethoprim) can interfere with memantine elimination 6
   • Such interactions could potentially lead to higher memantine levels and increased side effects

3. Assess renal function:

   • Patients with declining renal function may need dose adjustment 2, 3

4. Monitor urine pH:

   • Changes in dietary habits that alter urine pH can significantly affect memantine excretion 1
   • Acidic urine increases memantine clearance while alkaline urine decreases it

Clinical Decision Making

If urinary frequency is bothersome to the patient on memantine:

1. Evaluate benefit vs. burden:

   • Assess cognitive benefit from memantine against the impact of urinary symptoms on quality of life

2. Consider dose adjustment:

   • Particularly in patients with renal impairment or those taking interacting medications

3. Alternative options:

   • If urinary symptoms are severe and persistent, consider alternative treatments for dementia
   • Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) have different side effect profiles, though they may cause other gastrointestinal side effects 4

While urinary frequency is not highlighted as a primary side effect in the literature, the pharmacokinetic properties of memantine and its renal clearance pathway make it a plausible side effect that clinicians should be aware of when prescribing this medication.