1. Clinical Overview
Memantine is a low to moderate affinity, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. It is a disease-modifying agent used for the symptomatic treatment of moderate to severe Alzheimer's disease (AD) in the Indian context. It works by regulating glutamate activity, which is implicated in neuronal excitotoxicity and cognitive decline. Unlike acetylcholinesterase inhibitors, it acts on the glutamatergic system and is often used as monotherapy or in combination with donepezil.
| Onset | Duration | Bioavailability |
|---|---|---|
| Clinical improvement in cognition and global function may be observed within 4-12 weeks of initiating therapy. | The pharmacological effect correlates with its plasma half-life of approximately 60-80 hours, allowing for once-daily dosing. Therapeutic benefits are sustained with continuous treatment. | Approximately 100%. |
2. Mechanism of Action
Memantine acts as a low-to-moderate affinity, voltage-dependent, non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Under pathological conditions in Alzheimer's disease, chronic glutamate-mediated excitotoxicity via overactivation of NMDA receptors leads to neuronal damage and cell death. Memantine preferentially blocks NMDA receptor channels during prolonged, low-level activation (pathological tone) while allowing for normal physiological neurotransmission required for learning and memory.
3. Indications & Uses
- Moderate to Severe Alzheimer's Disease (as per DCGI approval in India)
4. Dosage & Administration
Adult Dosage: For Alzheimer's Disease: Start at 5 mg once daily. Increase dose in 5 mg increments weekly to the target maintenance dose of 20 mg/day. Recommended titration: Week 1: 5 mg/day; Week 2: 10 mg/day (5 mg twice daily); Week 3: 15 mg/day (10 mg AM, 5 mg PM); Week 4 and maintenance: 20 mg/day (10 mg twice daily).
Administration: Can be taken with or without food. Tablet should be swallowed whole with water. For patients on 20 mg/day, administer as 10 mg twice daily to minimize potential side effects. If a dose is missed, do not double the next dose. Resume the regular dosing schedule.
5. Side Effects
Common side effects may include:
- Dizziness
- Headache
- Constipation
- Somnolence (drowsiness)
- Hypertension
- Confusion (transient)
- Cough
- Back pain
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Drugs that alkalinize urine (e.g., Sodium Bicarbonate, Acetazolamide, Thiazides) | Increased plasma levels of memantine due to decreased renal elimination. | Moderate |
| NMDA Antagonists (e.g., Amantadine, Ketamine, Dextromethorphan) | Additive CNS and psychiatric side effects (dizziness, confusion, hallucinations). | Moderate |
| Cholinergic Agents (e.g., Donepezil, Rivastigmine, Galantamine, Bethanechol) | Pharmacodynamic synergy. Generally safe and used in combination, but may increase cholinergic side effects. | Mild |
| Drugs eliminated via renal tubular secretion (e.g., Cimetidine, Ranitidine, Quinidine, Nicotine) | Potential competition for excretion, may increase memantine levels. | Mild to Moderate |
| Levodopa, Dopaminergic Agonists | Potential increased dopaminergic effects and side effects. | Mild |
| Antipsychotics (Typical and Atypical) | May potentiate extrapyramidal symptoms (EPS) and other CNS effects. | Moderate |
| Barbiturates, Neuroleptics, Anticonvulsants, Alcohol | Additive sedative and CNS depressant effects. | Moderate |
7. Patient Counselling
- DO take the medicine exactly as prescribed by your doctor.
- DO follow the weekly dose increase schedule if you are just starting.
- DO inform all your doctors and dentists that you are taking memantine.
- DO keep a regular follow-up schedule with your neurologist/psychiatrist.
- DONT stop taking the medicine suddenly without consulting your doctor.
- DONT double the dose if you miss one. Skip it and take the next dose at the regular time.
- DONT crush or chew the tablets. Swallow whole with water.
- DONT take over-the-counter medicines (especially for cold/cough containing dextromethorphan) without consulting your doctor or pharmacist.
8. Toxicology & Storage
Overdose: Symptoms may include: restlessness, psychosis, visual hallucinations, somnolence, stupor, loss of consciousness, dizziness, agitation, aggression, diarrhea, confusion, syncope, weakness, bradycardia, hypertension, and seizures. Doses up to 200 mg have been reported with mostly mild symptoms.
Storage: Store at room temperature (15°C to 30°C). Protect from light and moisture. Keep in the original blister pack or container. Keep out of reach of children. Do not use after the expiry date printed on the pack.