Namenda - Drug Monograph

Introduction

Namenda (memantine hydrochloride) is an N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease. Developed by Merz Pharma and currently marketed by Allergan, it represents a distinct pharmacological approach to dementia management compared to acetylcholinesterase inhibitors.

Mechanism of Action

Memantine exerts its therapeutic effects through non-competitive, voltage-dependent antagonism of NMDA receptors. Under pathological conditions in Alzheimer's disease, excessive glutamate stimulation leads to calcium influx through NMDA receptors, resulting in excitotoxicity and neuronal damage. Memantine preferentially blocks these overactivated receptors while allowing normal synaptic transmission to continue, thereby modulating glutamatergic neurotransmission without completely inhibiting it.

Indications

• Treatment of moderate to severe Alzheimer's disease
• May be used as monotherapy or in combination with acetylcholinesterase inhibitors

Dosage and Administration

• Week 1: 5 mg once daily
• Week 2: 5 mg twice daily
• Week 3: 10 mg morning, 5 mg evening
• Week 4 and maintenance: 10 mg twice daily

• Oral administration with or without food
• Available as tablets, oral solution, and extended-release capsules
• For patients with severe renal impairment (CrCl 5-29 mL/min): Maximum dose 5 mg twice daily

• Renal impairment: Dose adjustment required
• Hepatic impairment: No specific recommendations (use with caution)
• Geriatric: No dosage adjustment necessary based on age alone

Pharmacokinetics

Contraindications

• Hypersensitivity to memantine or any component of the formulation
• Severe renal impairment (CrCl < 5 mL/min) due to inadequate clearance

Warnings and Precautions

• Seizure disorders: Use with caution in patients with epilepsy or conditions that lower seizure threshold
• Cardiac conditions: Caution in patients with recent myocardial infarction, uncompensated congestive heart failure
• Renal impairment: Dose adjustment required for moderate to severe impairment
• Urinary conditions: May increase urine pH; use cautiously in patients with alkaline urine
• Psychiatric symptoms: May cause agitation, hallucinations, or confusion
• Driving and operating machinery: May cause dizziness or somnolence

Drug Interactions

• NMDA antagonists: (amantadine, ketamine, dextromethorphan) - Increased risk of adverse effects
• Urinary alkalinizers: (carbonic anhydrase inhibitors, sodium bicarbonate) - May decrease memantine elimination
• Cimetidine: May increase memantine levels through renal tubular competition
• Hydrochlorothiazide: May increase memantine levels
• Nicotine: May decrease memantine levels

• Donepezil, galantamine, rivastigmine
• Warfarin, digoxin
• CYP450 substrates, inhibitors, or inducers

Adverse Effects

• Dizziness (7% vs 5% placebo)
• Headache (6% vs 4% placebo)
• Constipation (5% vs 3% placebo)
• Confusion (6% vs 5% placebo)
• Somnolence (3% vs 2% placebo)

• Seizures
• Hallucinations
• Psychiatric symptoms
• Hypertension
• Cardiac failure
• Pancreatitis (rare)

Monitoring Parameters

• Cognitive assessment: MMSE or similar tools at baseline and every 3-6 months
• Functional status: ADLs and IADLs assessment
• Behavioral symptoms: Neuropsychiatric Inventory
• Renal function: Serum creatinine and calculated CrCl at baseline and periodically
• Adverse effects: Regular assessment for dizziness, confusion, constipation
• Overall clinical status: Global assessment of change

Patient Education

• Take medication exactly as prescribed; do not exceed recommended dose
• Report any dizziness, confusion, or unusual behaviors to healthcare provider
• Maintain adequate fluid intake to prevent constipation
• Use caution when rising from sitting or lying position due to dizziness risk
• Inform all healthcare providers about memantine use
• Do not stop medication abruptly without consulting prescriber
• Store medication at room temperature away from moisture
• For oral solution: Use provided dosing device; not with other liquids

References

1. FDA Prescribing Information: Namenda (memantine HCl) 2. Reisberg B, et al. Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med. 2003;348(14):1333-1341 3. McShane R, et al. Memantine for dementia. Cochrane Database Syst Rev. 2019;3:CD003154 4. Peskind ER, et al. Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial. Am J Geriatr Psychiatry. 2006;14(8):704-715 5. Tariot PN, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004;291(3):317-324 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Alzheimer's Disease and Other Dementias. 2016 7. Lexicomp Online, Lexi-Drugs. Memantine. Wolters Kluwer Clinical Drug Information, Inc.