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Sunday, August 17, 2025

Memantine


Overview

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist used primarily in the management of moderate to severe Alzheimer’s disease. It provides symptomatic relief by modulating glutamatergic neurotransmission, which is thought to play a role in excitotoxicity and neuronal degeneration. Unlike cholinesterase inhibitors (donepezil, rivastigmine, galantamine), which target cholinergic dysfunction, memantine acts on the glutamatergic system.

It does not cure Alzheimer’s disease or stop progression but may stabilize or slow cognitive and functional decline. It is often prescribed alone or in combination with a cholinesterase inhibitor.

Pharmacological Class and Formulations

  • Class: NMDA receptor antagonist (anti-dementia drug)

  • ATC Code: N06DX01

  • Formulations:

    • Oral tablets (5 mg, 10 mg)

    • Oral solution (10 mg/5 mL)

    • Extended-release capsules (7 mg, 14 mg, 21 mg, 28 mg; available in some regions)

Mechanism of Action

  • Glutamatergic dysfunction is implicated in Alzheimer’s disease pathophysiology. Excessive stimulation of NMDA receptors by glutamate leads to excitotoxicity, neuronal calcium overload, and cell death.

  • Memantine binds to NMDA receptor-associated ion channels in a voltage-dependent, uncompetitive manner, preferentially under conditions of excessive glutamate activity.

  • This action helps normalize glutamatergic transmission while preserving physiological activation needed for learning and memory.

Pharmacokinetics

  • Absorption: Oral bioavailability ~100%.

  • Distribution: Widely distributed; low plasma protein binding (~45%).

  • Metabolism: Minimal hepatic metabolism; largely unchanged in plasma.

  • Elimination: Excreted unchanged in urine; renal clearance influenced by urine pH.

  • Half-life: 60–80 hours, supporting once-daily dosing in extended-release formulations.

Clinical Indications

  • Moderate to severe Alzheimer’s disease (monotherapy or in combination with cholinesterase inhibitors).

  • Other potential/off-label uses (under investigation, not routinely recommended):

    • Vascular dementia

    • Parkinson’s disease dementia

    • Dementia with Lewy bodies

    • Neuropathic pain, migraine prophylaxis, autism spectrum disorder (research use)

Contraindications

  • Hypersensitivity to memantine or excipients.

  • Severe uncontrolled epilepsy (use caution).

Precautions

  • Renal impairment: Dose adjustment required for severe impairment (CrCl 5–29 mL/min).

  • Hepatic impairment: Use caution in severe impairment.

  • Seizure disorders: May increase seizure risk.

  • Urinary pH: Alkaline urine (from diet or medications like carbonic anhydrase inhibitors, sodium bicarbonate) reduces clearance, increasing toxicity risk.

  • Combination therapy: Can be combined with cholinesterase inhibitors; monitor for additive side effects (confusion, dizziness).

Adverse Effects

Common

  • Dizziness

  • Headache

  • Confusion

  • Constipation

  • Hypertension

Less Common

  • Fatigue, somnolence

  • Hallucinations

  • Vomiting, abdominal pain

  • Anxiety, depression

Rare but Serious

  • Seizures

  • Hepatic dysfunction

  • Hypersensitivity reactions

Drug Interactions

  • NMDA antagonists (amantadine, ketamine, dextromethorphan): risk of additive adverse effects.

  • Drugs altering urine pH (acetazolamide, sodium bicarbonate): may reduce elimination and increase plasma levels.

  • Anticholinergics, dopaminergics: possible additive CNS effects.

  • Cimetidine, ranitidine, quinidine, nicotine, hydrochlorothiazide: may affect renal clearance.

Dosage

Adults with Alzheimer’s Disease

Immediate-release (IR) tablets/solution

  • Starting dose: 5 mg once daily.

  • Titration: Increase by 5 mg at weekly intervals.

  • Target dose: 20 mg/day, given as 10 mg twice daily.

Extended-release (ER) capsules

  • Starting dose: 7 mg once daily.

  • Titration: Increase by 7 mg at weekly intervals.

  • Target dose: 28 mg once daily.

Renal impairment

  • CrCl 30–49 mL/min: 10–20 mg/day (IR); 14–28 mg/day (ER).

  • CrCl 5–29 mL/min: Max 10 mg/day (IR) or 14 mg/day (ER).

  • CrCl <5 mL/min: Not recommended.

Hepatic impairment

  • Mild to moderate: No adjustment.

  • Severe: Use caution; data limited.

Monitoring

  • Baseline and during treatment:

    • Cognitive and functional status (MMSE or equivalent)

    • Blood pressure

    • Renal function (especially in elderly)

    • Psychiatric symptoms (hallucinations, depression, agitation)

Patient Counseling Points

  • Memantine does not cure Alzheimer’s disease but may slow worsening of symptoms.

  • Take exactly as prescribed; do not stop abruptly without consulting a clinician.

  • Report dizziness, fainting, hallucinations, or severe confusion.

  • Maintain hydration and avoid abrupt dietary changes that significantly alter urinary pH.

  • Family and caregivers should monitor adherence and behavioral changes.




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