Memantine Hydrochloride
Indications
Memantine Hydrochloride is used for:
Alzheimer's dementia.
Adult Dose
Oral
Moderate to severe dementia in Alzheimer's disease
Adult: As hydrochloride: Initially, 5 mg daily in the morning for the 1st wk; increase dose wkly in steps of 5 mg. Max: 20 mg daily. Wait for at least 1 wk between dose changes. Doses >10 mg/day should be given in 2 divided doses.
Suggested titration: 5 mg daily for >1 wk; 5 mg bid for >1 wk; 15 mg daily given in 5- and 10-mg separated doses for >1 wk; then 10 mg bid.
Hepatic impairment
Mild or moderate (Child Pugh A/B): No dosage adjustment required
Severe (Child Pugh C): Caution
Child Dose
Renal Dose
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.
Administration
May be taken with or without food.
Contra Indications
Hypersensitivity to memantine or components of the formulation. Severe renal impairment.
Precautions
Renal impairment; epilepsy. Pregnancy and lactation. Closely monitor patients with recent MI, uncompensated CHF, uncontrolled hypertension. Predisposition to convulsions; conditions that increase urinary pH.
Lactation: Unknown whether drug is excreted into breast milk; use with caution
Pregnancy-Lactation
Pregnancy
There are no adequate data on developmental risk associated with use; adverse developmental effects (decreased body weight, and skeletal ossification) observed in offspring of rats during pregnancy at doses associated with minimal maternal toxicity; doses are higher than used in humans at maximum recommended daily dose
Animal data
Oral administration to rats during period of organogenesis resulted in decreased skeletal ossification in fetuses at highest dose tested; the higher no-effect dose (6 mg/kg/day) was approximately 3 times MRHD on a mg/m² basis
Oral administration of memantine to rabbits during period of organogenesis resulted in no adverse developmental effects; highest dose tested was approximately 30 times the MRHD on a mg/m² basis
Oral administration to rats from late gestation throughout lactation to weaning, resulted in decreased pup weights at highest dose tested; the higher no-effect dose (6 mg/kg/day) is approximately 3 times the MRHD on a mg/ m² basis
Lactation
There are no data on presence of drug in human milk, effects on breastfed infant, or on milk production
Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition
Interactions
May increase effects of antimuscarinics and dopaminergics. May reduce effects of antipsychotics and barbiturates. May alter effects of dantrolene, baclofen. Reduced clearance with carbonic anhydrase inhibitors and sodium bicarbonate.
Potentially Fatal: Increased risk of adverse effects with amantadine, dextromethorphan or ketamine.
Side Effects
Side effects of Memantine Hydrochloride :
1-10%
Dizziness (7%), Confusion (6%), Headache (6%), Constipation (5%), Cough (4%), Hypertension (4%), Backache (3%), Pain (3%), Somnolence (3%), Syncope (3%), Vomiting (3%), Dyspnea (2%), Fatigue (2%)
<1%
Acute renal failure, Cerebral infarction, Cerebrovascular accident, Deep venous thrombosis, Hepatitis, liver failure, Intracranial hemorrhage, Neuroleptic malignant syndrome, Seizure (including grand mal), Stevens-Johnson syndrome, Transient ischemic attack
Mode of Action
Memantine, a derivative of amantadine, is a noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist. It affects transmission of glutamate, the primary 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.