Memantine: English spelling of memantin
Memantine is the internationally used English spelling of the substance memantin. In English summaries of product characteristics, product names and the international literature this form is used throughout (brand names Namenda in the USA, Axura and Ebixa in the EU, generics). In Germany the German spelling memantin is widespread. Pharmacologically the same substance is meant.
Memantin was originally developed in 1968 as a glucose-lowering agent, later recharacterised as a non-competitive NMDA receptor antagonist and approved in the EU in 2002 for moderate to severe Alzheimer's dementia. Memantine thus complements the therapeutic spectrum dominated in early stages by cholinesterase inhibitors such as donepezil, rivastigmine and galantamine.
Mechanism of action
Under normal conditions, the NMDA receptor (N-methyl-D-aspartate receptor) is activated by glutamate and is central to learning, memory and neuronal plasticity. In Alzheimer's and other neurodegenerative diseases, pathologically elevated and chronic glutamate release leads to over-stimulation of the NMDA receptor, resulting in excitotoxicity, calcium influx and neuronal damage.
Memantine is a non-competitive, voltage-dependent NMDA receptor antagonist with moderate affinity and a fast off-rate. It binds in the ion channel of the NMDA receptor and blocks it, mainly under pathological conditions with continuously activated receptor. With normal synaptic activity memantine dissociates fast enough not to impair physiological function.
The result is reduction of pathological over-stimulation without blocking normal NMDA-mediated signalling. Clinically this gives moderate effects on cognition, behaviour and daily function, especially at more advanced stages.
Indications
- Moderate to severe Alzheimer's dementia: approved in the EU and internationally, monotherapy or in combination with a cholinesterase inhibitor
- Off-label uses: vascular dementia, mixed dementia, behavioural symptoms in dementia, aphasia, autism spectrum, neuropathic pain, tinnitus
In mild Alzheimer's dementia memantine is not approved in the EU as studies do not show a clear benefit there.
Dosing and administration
Titration:
- Week 1: 5 mg once daily in the morning
- Week 2: 10 mg per day in two divided doses
- Week 3: 15 mg per day
- From week 4: 20 mg per day (maintenance dose)
Take regardless of meals. Memantine is also available as oral solution which can be dosed more precisely.
Renal impairment: with moderate impairment (CrCl 30 to 49 ml/min) the dose is limited to 10 mg per day; with severe impairment (CrCl 5 to 29 ml/min) to 10 mg, with maintenance 5 mg per day.
With alkaline urine, plasma concentration rises, which may be relevant in vegetarian diet or concomitant therapy with acetazolamide.
Side effects
Common: dizziness, headache, drowsiness, constipation, hypertension, dyspnoea.
Uncommon: fatigue, confusion, hallucinations, fungal infections, vomiting, gait instability, worsening heart failure, venous thromboembolism.
Rare and very rare: seizures, pancreatitis, hepatitis, psychosis, severe skin reactions, allergic reactions.
Important points:
- Memantine is generally well tolerated, severe side effects are rare
- Hallucinations occur mainly with higher doses or rapid titration, hence stepwise titration is important
- Patients with a history of seizures need cautious use
- With acute worsening of cognitive or physical symptoms, side effects or interactions should be considered
Interactions
- Other NMDA antagonists (amantadine, ketamine, dextromethorphan): additive effect, risk of pharmacotoxic psychosis, avoid combination
- L-dopa, dopamine agonists, anticholinergics: potentiation possible
- Barbiturates, neuroleptics: possible antagonistic effect
- Acetazolamide, sodium bicarbonate: elevation of urine pH, reducing renal excretion of memantine, raising levels
- Hydrochlorothiazide: reduced diuretic efficacy
- Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine: theoretical competition for the renal cation transport system
- Warfarin: isolated reports of INR rise
Special considerations
Pregnancy and breastfeeding: not relevant in the dementia indication; in off-label use, individual assessment, since data are limited.
Renal impairment: dose adjustment necessary, regular monitoring of renal function sensible.
Seizures: caution in patients with a history of seizure disorders, since memantine can lower the seizure threshold.
Sleep-wake rhythm: some patients benefit from a morning intake, since insomnia has been observed.
Measure therapy success: the effect of memantine is usually subtle. Clinical assessment with standardised tests (MMSE, ADAS-Cog) and observation of daily function over 3 to 6 months is sensible. If no stabilisation or improvement is seen, discontinuation can be considered.
Family support: dementia is a disease that affects more than just the patient. Relatives benefit from information about realistic therapy expectations, self-help groups and counselling.
Related substances
- Donepezil, cholinesterase inhibitor
- Galantamine, cholinesterase inhibitor with nicotinic modulation
- Donezepil, alternative spelling of donepezil
- Buspirone, anxiolytic for accompanying dementia symptoms
Frequently asked questions
Is the substance called memantine or memantin?
Memantine is the international and English spelling. Memantin is the German form. Both refer to the same substance from the class of NMDA receptor antagonists.
Does memantine cure Alzheimer's?
No. Memantine can temporarily slow the course of moderate to severe Alzheimer's dementia and ease symptoms such as agitation or apathy. A cure or halting of the underlying neurodegeneration is not possible. Realistic expectations help avoid disappointment.
What is the difference between memantine and donepezil?
Donepezil inhibits the enzyme acetylcholinesterase and increases cholinergic signalling. Memantine modulates the glutamatergic system via NMDA receptors. Both can be combined, which is often sensible in moderate to severe dementia. Donepezil is indicated from mild to severe Alzheimer's dementia, while memantine is approved only from the moderate stage.
When should memantine be stopped?
When clinical benefit is absent or the disease has reached a very advanced stage at which no meaningful improvement of quality of life can be achieved. The decision is made together with patients, relatives and the treating physician, taking the individual situation into account.
Sources
- EMA Ebixa (memantine) EPAR
- BfArM Federal Institute for Drugs and Medical Devices
- AWMF S3 dementia guideline
- Gelbe Liste memantin monograph
Legal notice and disclaimer
The information on this page is provided for general information purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Medicines should only be used after a doctor's prescription or pharmacy supply. All information is based on summaries of product characteristics and accepted scientific sources at the time of writing; the current SmPC of the manufacturer is always decisive. Sanoliste accepts no liability for completeness, timeliness or accuracy. In a medical emergency, dial the emergency number 112.