Memanto

Approved Indications:

• Moderate to Severe Alzheimer’s Disease: Indicated for the treatment of moderate to severe dementia of the Alzheimer’s type. Can be used as monotherapy or in combination with acetylcholinesterase inhibitors (e.g., donepezil).

Clinically Accepted Off-label Uses:

• Mild Alzheimer’s Disease: Occasionally used, although evidence is limited for efficacy in mild stages.
• Vascular Dementia: Used in selected patients with cognitive impairment of cerebrovascular origin.
• Parkinson’s Disease Dementia: Considered in patients with cognitive deficits not adequately controlled with standard therapy.
• Dementia with Lewy Bodies: Employed cautiously to manage cognitive and behavioral symptoms.
• HIV-associated Neurocognitive Disorders (HAND): Investigational use to attenuate glutamate-mediated excitotoxicity.
• Autism Spectrum Disorder (ASD): Studied as adjunct therapy for irritability and behavioral dysregulation.
• Cognitive Impairment in Multiple Sclerosis: Explored off-label for attention and memory enhancement.

Route of Administration: Oral
Available Forms: Immediate-release tablets, oral solution, extended-release capsules

Adults (Moderate to Severe Alzheimer’s Disease)

Immediate-Release Tablets:

• Starting Dose: 5 mg once daily
• Titration: Increase by 5 mg weekly in divided doses
• Maintenance Dose: 10 mg twice daily (20 mg/day)

Extended-Release Capsules:

• Starting Dose: 7 mg once daily
• Titration: Increase by 7 mg weekly
• Maximum Dose: 28 mg once daily

Oral Solution:

• Dosage equivalent to tablet; use accurate measuring device.

Elderly:

• Same as adult dosage; monitor for increased sensitivity.

Pediatric Population:

• Not approved for use in children or adolescents under 18 years.

Renal Impairment:

• CrCl ≥50 mL/min: No dose adjustment
• CrCl 30–49 mL/min:
• IR: Max 10 mg twice daily
• ER: Max 14 mg once daily
• CrCl <30 mL/min:
• IR: Max 5 mg twice daily
• ER: Max 14 mg once daily

Hepatic Impairment:

• Mild to Moderate: Use with caution; no specific adjustment required
• Severe: Use not recommended due to limited data

Memantine is an uncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist that selectively binds to NMDA receptor-operated cation channels. In Alzheimer’s disease, excessive glutamate release leads to persistent activation of NMDA receptors, causing sustained calcium influx and excitotoxic neuronal injury. Memantine inhibits this pathological activation without interfering with normal synaptic transmission, thus offering neuroprotective effects while preserving cognitive and functional abilities.

• Absorption: Rapidly absorbed; oral bioavailability ~100%
• Time to Peak Concentration: 3–8 hours (IR), 9–12 hours (ER)
• Distribution: Widely distributed; volume of distribution 9–11 L/kg
• Plasma Protein Binding: ~45%
• Metabolism: Minimal hepatic metabolism; primarily through hydroxylation and conjugation
• Active Metabolites: No significant active metabolites
• Half-life: 60–80 hours
• Excretion: Mainly via kidneys (unchanged); involves active tubular secretion
• Clearance: Reduced in renal impairment

Pregnancy:

• FDA Category: C (prior classification)
• Narrative Summary: Animal studies show adverse fetal effects. There are no adequate human studies. Use only if the potential benefit outweighs the risk.

Lactation:

• Excretion in human milk is unknown. Animal data suggest excretion in breast milk. Due to the potential for adverse effects in the nursing infant, breastfeeding is not recommended during treatment.

• Primary Class: Anti-dementia agent
• Subclass: NMDA receptor antagonist
• Category: Central Nervous System (CNS) drug

• Known hypersensitivity to memantine or any component of the formulation
• Use in severe renal impairment without appropriate dose adjustment
• Concurrent use with other NMDA antagonists (e.g., amantadine, ketamine) without clinical oversight

• Seizure Risk: Use with caution in patients with history of seizures
• Renal Dysfunction: Dose adjustment required; monitor renal function
• Urinary Alkalinization: May increase drug levels by reducing excretion
• Neuropsychiatric Symptoms: Can cause agitation, confusion, or hallucinations
• Falls: May increase fall risk due to dizziness or hypotension
• Driving or Operating Machinery: Use caution until individual response is known
• Severe Hepatic Impairment: Use not recommended due to insufficient data

Common (≥5%):

• Nervous System: Dizziness, headache, confusion
• Gastrointestinal: Constipation
• Psychiatric: Hallucinations, agitation
• General: Hypertension, fatigue

Less Common (<5%):

• Vomiting, somnolence, anxiety, weight loss, urinary incontinence

Serious or Rare:

• Seizures
• Stevens-Johnson syndrome
• Hepatic dysfunction
• Rhabdomyolysis
• Bradycardia or syncope

Timing & Severity: Adverse effects are generally mild and dose-dependent; more likely during initiation or dose escalation.

Pharmacodynamic Interactions:

• Other NMDA Antagonists (amantadine, ketamine, dextromethorphan): Increased risk of CNS toxicity
• Carbonic Anhydrase Inhibitors & Sodium Bicarbonate: Can alkalinize urine, decreasing drug excretion and increasing systemic levels

Pharmacokinetic Considerations:

• Not significantly metabolized by CYP enzymes; minimal CYP450 involvement
• No major enzyme inhibition or induction expected

Food Interactions:

• No significant food effects; may be taken with or without food

Alcohol:

• May potentiate CNS depressant effects such as dizziness and confusion

• FDA/EMA (2023–2024): No recent updates to memantine labeling
• NICE Guidelines: Continue recommending memantine for moderate-to-severe Alzheimer’s, alone or in combination with acetylcholinesterase inhibitors
• Clinical Use: Ongoing research into benefits in other neurodegenerative conditions, but no new approved indications

• Temperature: Store at 20°C to 25°C (68°F to 77°F); allowable range 15°C to 30°C
• Humidity & Light: Protect from moisture and light
• Oral Solution: Shake well before use; use calibrated measuring device
• Handling Precautions: Do not freeze; store in original container
• Reconstitution/Refrigeration: Not required