Usage
Memantine is prescribed for the treatment of moderate to severe dementia of the Alzheimer’s type. It is classified as an NMDA receptor antagonist. Memantine works by regulating the activity of glutamate, a neurotransmitter involved in learning and memory. Overexcitation of NMDA receptors by glutamate is thought to contribute to the symptoms of Alzheimer’s disease. Memantine modulates the effects of glutamate, potentially protecting neurons from damage.
Alternate Names
Memantine hydrochloride is the chemical name. Brand names include Namenda, Ebixa, Nemdatine, and Valios. Namzaric is a brand name for a combination of memantine and donepezil.
How It Works
Pharmacodynamics: Memantine is a low-to-moderate affinity uncompetitive NMDA receptor antagonist. This means it preferentially blocks excessive NMDA receptor activity without disrupting normal neurotransmission. By blocking the effects of excessive glutamate, memantine may protect neurons from excitotoxicity, a process implicated in the progression of Alzheimer’s disease.
Pharmacokinetics: Memantine is well-absorbed after oral administration, reaching peak plasma concentrations in 3-8 hours. It is primarily eliminated by the kidneys, with a half-life of 60-80 hours. Metabolism is minimal, with a small fraction metabolized by the liver. It does not significantly induce or inhibit CYP450 enzymes.
Mode of Action: Memantine binds to the NMDA receptor within the ion channel pore, blocking the excessive influx of calcium ions induced by pathological levels of glutamate. This mechanism helps to prevent excitotoxicity and neuronal dysfunction.
Elimination Pathways: Primarily renal excretion. Minimal hepatic metabolism.
Dosage
Standard Dosage
Adults:
- Immediate-Release Tablets:
- Starting dose: 5 mg once daily.
- Titration: Increase in 5 mg increments weekly (5 mg BID, 5 mg and 10 mg as separate doses) up to a maximum of 20 mg daily (10 mg BID).
- Extended-Release Capsules:
- Starting dose: 7 mg once daily.
- Titration: Increase in 7 mg increments weekly up to a maximum of 28 mg once daily.
Children:
Use of memantine in children is not recommended due to lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Standard dosage adjustments may be applied, with careful monitoring for side effects.
- Patients with Renal Impairment:
- Moderate to severe renal impairment (creatinine clearance 5-29 mL/min): Maximum dose of 10 mg/day (immediate-release) or 14 mg/day (extended-release).
- Patients with Hepatic Dysfunction:
- Mild to moderate hepatic impairment: No dose adjustment required.
- Severe hepatic impairment: Use with caution, and dose reduction may be considered. No data exists for extended-release capsules in this scenario.
- Patients with Comorbid Conditions: Careful monitoring and possible dosage adjustments may be required, particularly in patients with epilepsy, cardiovascular disease, or conditions affecting urine pH.
Clinical Use Cases
Memantine’s indicated use is limited to moderate to severe Alzheimer’s dementia. There are research studies exploring its potential in other conditions (e.g., traumatic brain injury, neuropathic pain, status epilepticus), but these are not established clinical uses. Dosing in these contexts is not standardized.
Dosage Adjustments
Adjustments are necessary in cases of renal or hepatic impairment, as detailed above. Conditions affecting urine pH may require dose modification. Interruptions in treatment may necessitate re-titration. Switching from immediate-release to extended-release should follow specific guidelines.
Side Effects
Common Side Effects
Dizziness, headache, confusion, constipation, and hallucinations.
Rare but Serious Side Effects
Stevens-Johnson syndrome, seizures, acute renal failure, pancreatitis, hepatitis, suicidal ideation.
Long-Term Effects
Potential chronic complications from prolonged use are not fully characterized but may include worsening of cognitive function in certain individuals.
Adverse Drug Reactions (ADR)
Severe hypersensitivity reactions, severe neuropsychiatric events, and significant cardiac or liver dysfunction are ADRs needing immediate attention.
Contraindications
Hypersensitivity to memantine or any of its excipients.
Drug Interactions
Drugs that alkalinize urine (e.g., sodium bicarbonate, carbonic anhydrase inhibitors) can reduce memantine clearance. Concomitant use of other NMDA antagonists (e.g., amantadine, ketamine) may enhance NMDA receptor blockade. Interactions with commonly used drugs like antibiotics, anticoagulants, or antihypertensives are generally not clinically significant, though some caution is required with metformin due to its renal elimination.
Pregnancy and Breastfeeding
The safety of memantine during pregnancy and breastfeeding has not been established. Use only if the potential benefit outweighs the potential risk to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: NMDA receptor antagonist, modulating glutamate activity.
- Side Effects: Dizziness, headache, confusion, constipation, hallucinations; rarely, severe reactions.
- Contraindications: Hypersensitivity to memantine.
- Drug Interactions: Drugs that alkalinize urine, other NMDA antagonists.
- Pregnancy & Breastfeeding: Safety not established.
- Dosage: Refer to detailed section above.
- Monitoring Parameters: Cognitive function, renal function, liver function, psychiatric status.
Popular Combinations
Memantine is sometimes used in combination with cholinesterase inhibitors (e.g., donepezil) in moderate to severe Alzheimer’s disease. The rationale is to target multiple neurotransmitter systems involved in the disease process.
Precautions
Pre-existing conditions such as epilepsy, cardiovascular disease, renal impairment, and hepatic impairment require careful evaluation and monitoring. Conditions impacting urine pH should be considered. Lifestyle advice may include restrictions on driving.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Memantine?
A: The standard adult dosage for immediate-release memantine is 20 mg per day, achieved through weekly titration. The extended-release formulation is dosed at 28 mg per day following titration. Adjustments are necessary for patients with renal impairment. Pediatric use is not recommended.
Q2: How does memantine differ from cholinesterase inhibitors?
A: Memantine is an NMDA receptor antagonist, while cholinesterase inhibitors boost acetylcholine levels. They work through different mechanisms but both aim to improve cognitive function in Alzheimer’s disease.
Q3: What are the most common side effects of memantine?
A: Dizziness, headache, confusion, and constipation are the most common side effects.
Q4: Can memantine be used in mild Alzheimer’s disease?
A: Clinical trials have not shown significant benefit in mild Alzheimer’s disease.
Q5: Are there any contraindications to using memantine?
A: Known hypersensitivity to memantine is a contraindication.
Q6: Does memantine interact with other medications?
A: Drugs that alkalinize urine can reduce memantine clearance. Other NMDA antagonists can have additive effects.
Q7: Can memantine be used during pregnancy or breastfeeding?
A: The safety in pregnancy and breastfeeding has not been established. Use only if the potential benefits outweigh the risks.
Q8: How should memantine be administered?
A: Memantine can be administered orally with or without food. Immediate-release tablets can be divided, but extended-release capsules should be swallowed whole or sprinkled on applesauce.
Q9: How long does it take for memantine to work?
A: The full therapeutic effect of memantine may take several weeks to become apparent, as dosage is titrated gradually.
Q10: What should be monitored in patients taking memantine?
A: Cognitive function, renal and liver function, psychiatric status, and adverse reactions should be monitored.
