What is the recommended dosing and prescribing guidelines for Namenda (memantine) in patients with Alzheimer's disease?

Namenda (Memantine) Prescribing Guidelines for Alzheimer's Disease

Memantine is indicated for the treatment of moderate to severe dementia of the Alzheimer's type, with a recommended dosing regimen starting at 5 mg once daily and titrating to a target dose of 20 mg/day divided into two doses. 1

Dosing Protocol

Initial Dosing and Titration

• Start with 5 mg (2.5 mL) once daily
• Increase dose in 5 mg increments according to this schedule:
  • Week 1: 5 mg once daily
  • Week 2: 10 mg/day (5 mg twice daily)
  • Week 3: 15 mg/day (5 mg and 10 mg as separate doses)
  • Week 4: 20 mg/day (10 mg twice daily) - maintenance dose 1

Administration Guidelines

• Can be taken with or without food
• Minimum interval between dose increases should be one week
• If doses are missed for several days, restart at lower dose and retitrate
• For oral solution: use provided syringe to administer; do not mix with other liquids 1

Special Populations

Renal Impairment

• For severe renal impairment (creatinine clearance 5-29 mL/min): reduce target dose to 5 mg twice daily 1

Hepatic Impairment

• Administer with caution in patients with severe hepatic impairment 1

Extended-Release Formulation

• Namenda XR (memantine extended-release) is available as a 28 mg once-daily capsule
• Offers convenience of once-daily dosing which may improve adherence
• Capsules may be opened and contents sprinkled on applesauce for patients with difficulty swallowing 2

Efficacy and Clinical Use

Indications

• FDA-approved for moderate to severe Alzheimer's disease 1
• Evidence supports use as monotherapy or in combination with cholinesterase inhibitors 3

Efficacy Evidence

• Memantine shows statistically significant improvement in cognition for moderate to severe Alzheimer's disease 4
• When added to stable donepezil treatment, memantine demonstrates significant benefits in cognition, activities of daily living, global outcomes, and behavior compared to placebo 3
• Studies show memantine is well-tolerated for at least one year of treatment 5

Monitoring and Discontinuation

Monitoring

• Assess response after 6-12 months of treatment
• Look for stabilization or slowing of cognitive decline, improvement in functional abilities, and changes in behavior 6

Discontinuation Criteria

Consider discontinuing memantine after >12 months if:

• Clinically meaningful worsening of dementia over past 6 months not attributable to other causes
• No observed clinical benefit during treatment
• Development of severe or end-stage dementia
• Intolerable side effects (confusion, dizziness, falls)
• Poor medication adherence 4

Discontinuation Protocol

• Reduce dose gradually: decrease by 50% every 4 weeks until reaching initial starting dose
• After 4 weeks at starting dose, discontinue completely
• Consider reinitiating treatment if patient shows clinically meaningful worsening after discontinuation 4

Common Adverse Effects

• Most common adverse events (≥5% and greater than placebo): dizziness, headache, confusion, and constipation 1
• Withdrawal rates due to adverse effects range from 9-12% 4
• Caution: conditions that raise urine pH may decrease memantine elimination, resulting in increased plasma levels 1

Important Clinical Considerations

• Do not discontinue memantine in patients with clinically meaningful psychotic symptoms, agitation, or aggression until these symptoms have stabilized 4
• Continue treatment in patients who have shown reduction in neuropsychiatric symptoms even if cognitive and functional decline is evident 4
• Memantine should be discontinued for patients with mild cognitive impairment 4

By following these evidence-based guidelines for memantine prescribing, clinicians can optimize treatment outcomes while minimizing adverse effects in patients with moderate to severe Alzheimer's disease.