Memantine

Oral
Moderate dementia in Alzheimer's disease, Severe dementia in Alzheimer's disease
Adult: Initially, 5 mg once daily for the 1st wk, increased in wkly increments of 5 mg. Max: 20 mg daily.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
5-29	Max: 10 mg daily.
30-49	10 mg daily (after initial dose of 5 mg daily), if well tolerated for at least 7 days, may increase to 20 mg daily.

May be taken with or without food.

Patient w/ CV disease, epilepsy, history of convulsions or those w/ predisposing factors for epilepsy. Conditions that may increase urinary pH (e.g. drastic dietary changes). Moderate to severe renal and severe hepatic impairment. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery. Monitoring Parameters Monitor cognitive function; periodic ophth examination.

Headache, dizziness, constipation, HTN, somnolence, anxiety, confusion, hallucinations, fatigue, abnormal gait, hypertonia, vomiting, fungal infections, cystitis, thromboembolism, increased libido, psychotic reactions, pancreatitis; agranulocytosis, leucopenia (including neutropenia), thrombocytopenia, pancytopenia, thrombotic thrombocytopenic purpura, CHF, hepatitis, suicidal ideation, acute renal failure (including increased creatinine and renal impairment), Stevens-Johnson syndrome.

Symptoms: Agitation, asthenia, bradycardia, vomiting, dizziness, vertigo, ECG changes, increased BP, visual hallucinations, confusion, lethargy, restlessness, slowed movement, somnolence, stupor, unsteady gait, weakness, loss of consciousness, psychosis, coma. Management: Symptomatic and supportive treatment. May increase elimination by urinary acidification.

Increased risk of adverse effects w/ amantadine, ketamine or dextromethorphan. May decrease the effects of barbiturates and neuroleptics. May increase the effects of L-dopa, dopaminergic agonists and anticholinergics. May alter the effect of antispasmodics (e.g. dantrolene, baclofen). Decreased clearance w/ carbonic anhydrase inhibitors and Na bicarbonate. May potentially increase plasma levels of cimetidine, procainamide, ranitidine, quinidine, quinine, nicotine. May decrease serum level of hydrochlorothiazide.

Memantine, a derivative of amantadine, is a noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist which binds preferentially to NMDA-receptor-operated cation channels. It blocks the action of glutamate, the principal excitatory neurotransmitter in the CNS. Glutamate may contribute to the pathogenesis of Alzheimer's disease by overstimulating various glutamate receptors resulting in excitotoxicity and neuronal cell death.
Absorption: Well absorbed. Absolute bioavailability: Approx 100%. Time to peak plasma concentration: Approx 3-8 hr.
Distribution: Volume of distribution: 9-11 L/kg. Plasma protein binding: Approx 45%.
Metabolism: Undergoes partial hepatic metabolism to main metabolites including N-3,5-dimethyl-gludantan and 1-nitroso-3,5-dimethyl-adamantane.
Excretion: Mainly via urine (approx 57-82% as unchanged drug). Terminal half-life: 60-100 hr.

Oral: Store between 20-25°C.

Neurodegenerative Disease Drugs

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