Pharmacological Class:
N-methyl-D-aspartate (NMDA) receptor antagonist + acetylcholinesterase inhibitor.
Active Ingredient(s):
Memantine HCl extended-release, donepezil HCl; 14mg/10mg, 28mg/10mg; capsules.
Company
Actavis
Indication(s):
Moderate-to-severe dementia of the Alzheimer's type in patients stabilized on memantine HCl and donepezil HCl.
Pharmacology:
Memantine is postulated to exert its therapeutic effect through its action as a low-to-moderate affinity uncompetitive (open channel) NMDA receptor antagonist which binds preferentially to the NMDA receptor-operated cation channels. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is achieved by increasing the concentration of acetylcholine in the central nervous system through reversible inhibition of its hydrolysis by acetylcholinesterase.
Clinical Trials:
The efficacy of Namzaric as treatment for moderate to severe Alzheimer's disease was shown by its bioequivalence with co-administered memantine HCl ext-rel and donepezil HCl.
The efficacy of memantine HCl ext-rel was eva luated in a randomized, double-blind clinical study (n=677) in patients receiving acetylcholinesterase inhibitor (AChEI) therapy for 3 months prior to screening. Co-primary efficacy parameters of Severe Impairment Battery (SIB) and the Clinician's Interview-Based Impression of Change (CIBIC-Plus) were used. Patients were randomized to memantine HCl ext-rel 28mg/day or placebo, while receiving an AChEI (either donepezil, galantamine, or rivastigmine). At 24 weeks of treatment, the mean difference in the SIB change scores was 2.6 units and the CIBIC-Plus was 0.3 units for memantine HCl ext-rel vs. placebo. Using an LOCF analysis, memantine HCl ext-rel + AChEI was statistically significantly superior to placebo + AChEI.
The efficacy of donepezil HCl was eva luated in a randomized, double-blind, placebo-controlled study (n=248) in patients with severe Alzheimer's disease. A dual outcome assessment strategy eva luated cognitive function using an instrument designed for more impaired patients and overall function through caregiver-rated assessment. At 6 weeks of treatment, the mean difference in the SIB change scores was 5.9 points and the ADCS-ADL-severe change scores was 1.8 points for donepezil HCl treated patients vs. placebo. Donepezil HCl treatment was statistically significantly superior to placebo.
For more clinical trial data, see full labeling.
Legal Classification:
Rx
Adults:
Start the day after last dose of memantine HCl and donepezil HCl given separately. Swallow whole or may open caps and sprinkle on applesauce, then consume entire contents; do not divide doses. Previously stabilized on both components: 28mg/10mg once daily in the evening. Severe renal impairment (CrCl 5–29mL/min): 14mg/10mg once daily.
Children:
Not established.
Warnings/Precautions:
Cardiac conduction abnormalities. Peptic ulcer. Monitor for GI bleeding. GU obstruction. Alkalinized urine (eg, renal tubular acidosis, severe UTI) increases memantine levels. Seizures. Asthma or COPD. Severe hepatic impairment. Pregnancy (Category C). Nursing mothers.
Interaction(s)
Caution with other NMDA antagonists (eg, amantadine, ketamine, dextromethorphan). Memantine plasma levels may be increased by urinary alkalinizers. Donepezil potentiated by CYP3A4 (eg, ketoconazole) and CYP2D6 (eg, quinidine) inhibitors. CYP3A4 inducers (eg, phenytoin, carbamazepine, dexamethasone, rifampin, phenobarbital) may increase the rate of elimination of donepezil. Antagonizes anticholinergics. May potentiate succinylcholine-type muscle relaxants, other cholinesterase inhibitors, cholinergic agonists (eg, bethanechol). Concomitant NSAIDs may increase risk of GI bleed.
Adverse Reaction(s)
Headache, diarrhea, dizziness, anorexia, vomiting, nausea, ecchymosis.
How Supplied:
Caps—30, 90
LAST UPDATED:
7/31/2015
