Memantine

Oral
Moderate dementia in Alzheimer's disease, Severe dementia in Alzheimer's disease

CrCl (mL/min)	Dosage
5-29	As conventional tab or oral solution: Max: 10 mg daily. As extended-release cap: Max: 14 mg once daily.
30-49	As conventional tab or oral solution: 10 mg daily (after initial dose of 5 mg daily); if well tolerated for at least 1 week, may increase up to 20 mg daily based on standard titration scheme.

Severe: Not recommended.

May be taken with or without food.

Patient with epilepsy, history of seizure disorder or predisposing factors for epilepsy; CV disease (e.g. uncontrolled hypertension, recent MI, uncompensated CHF); conditions that may increase urinary pH including drastic dietary changes (e.g. from high-protein to vegetarian diet), renal tubular acidosis, severe UTI, and concomitant use of alkalinising agents (e.g. Na bicarbonate, carbonic anhydrase inhibitors). Avoid concomitant use with other NMDA antagonists (e.g. amantadine, ketamine, dextromethorphan). Renal and severe hepatic impairment. Pregnancy and lactation.

Significant: Hypersensitivity reactions (e.g. Stevens-Johnson syndrome); neuropsychiatric effects (e.g. headache, confusion, dizziness, drowsiness, sleep disturbance, ataxia, falling, impaired or loss of consciousness, agitation, delusion, hallucinations). Rarely, seizures.
Cardiac disorders: Heart failure.
Gastrointestinal disorders: Constipation, diarrhoea, vomiting, pancreatitis.
General disorders and administration site conditions: Fatigue.
Investigations: Elevated LFT.
Hepatobiliary disorders: Hepatitis.
Infections and infestations: Fungal infections.
Musculoskeletal and connective tissue disorders: Back pain.
Nervous system disorders: Abnormal gait, balance disorders.
Psychiatric disorders: Anxiety, depression, psychotic reactions, suicidal ideation.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea.
Vascular disorders: Hypertension, venous thrombosis or thromboembolism.

PO: B

Reassess the dosing and patient's tolerance regularly, preferably within 3 months after start of therapy, then reassess the clinical benefit and patient's tolerance according to latest clinical guidelines. Monitor cognitive function.

Symptoms: Dizziness, drowsiness, vertigo, vomiting, diarrhoea, ECG changes, bradycardia, increased blood pressure, lethargy, weakness, restlessness, unsteady gait, confusion, diplopia, agitation, aggression, visual hallucinations, psychosis, stupor, loss of consciousness, and coma. Management: Symptomatic and supportive treatment. May perform appropriate standard clinical procedures for drug removal including gastric lavage, use of activated charcoal, forced diuresis, and urine acidification (to enhance elimination).

Adverse reactions (primarily CNS-related) may be more pronounced or frequent when used with other NMDA antagonists (e.g. amantadine, ketamine, dextromethorphan). May increase the therapeutic effects of levodopa, dopaminergic agonists and anticholinergics. May decrease the therapeutic effects of barbiturates and neuroleptics. May alter the effects of dantrolene or baclofen. Concomitant use of memantine with drugs that are secreted by the same renal cationic system (e.g. cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine) may alter plasma concentrations of 1 or both drugs. May decrease the serum level of hydrochlorothiazide. Concomitant use with alkalinising drugs (e.g. Na bicarbonate, carbonic anhydrase inhibitors) may potentially decrease memantine clearance, which may result in increased adverse effects.

Description:
Mechanism of Action: Memantine is a voltage-dependent, low- to moderate-affinity uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, which binds to NMDA receptor-operated cation channels. It is thought to act by blocking the actions of glutamate, the primary excitatory neurotransmitter in the CNS. Continuous activation of CNS NMDA receptors by glutamate has been suggested as a potential cause of neurodegeneration observed in different forms of dementia, including dementia of the Alzheimer's type.
Pharmacokinetics:
Absorption: Well absorbed. Absolute bioavailability: Approx 100%. Time to peak plasma concentration: 3-8 hours (conventional forms); 9-12 hours (extended-release cap).
Distribution: Volume of distribution: 9-11 L/kg. Plasma protein binding: Approx 45%.
Metabolism: Undergoes partial metabolism in the liver; primary metabolites include N-3,5-dimethyl-gludantan, the isomeric mixture of 4- and 6-hydroxy-memantine and 1-nitroso-3,5-dimethyl-adamantane.
Excretion: Mainly via urine (74%; approx 48% as unchanged drug). Terminal elimination half-life: 60-100 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4054, Memantine. https://pubchem.ncbi.nlm.nih.gov/compound/Memantine. Accessed Mar. 25, 2024.

Store between 15-30°C.

Neurodegenerative Disease Drugs

N06DX01 - memantine ; Belongs to the class of other anti-dementia drugs.

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Memxa 10 mg Tablet (Medispec [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 14/02/2024.

Memxa 5 mg/0.5 mL Oral Solution (Medispec [M] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 14/02/2024.

Pharmacy Retailing t/a Healthcare Logistics. Ebixa 10 mg Film-coated Tablets data sheet 22 June 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 14/02/2024.