Memantine + Donepezil
Indications
Memantine + Donepezil is used for:
Alzheimer Disease
Adult Dose
Alzheimer Disease
Fixed dose combination product for patients with moderate-to-severe Alzheimer disease currently stabilized on donepezil 10 mg once daily
Recommended dose is 28 mg/10 mg PO qDay
Child Dose
Renal Dose
Severe renal impairment
Severe renal impairment (CrCl 5-29 mL/min, based on the Cockcroft-Gault equation)
Stabilized on donepezil 10 mg/day and not currently on memantine
Recommended starting dose: 7 mg/10 mg PO taken once daily in the evening
The dose should be increased to the recommended maintenance dose of 14 mg/10 mg once daily in the evening after a minimum of 1 week
Stabilized on both donepezil and memantine
Patients on memantine (5 mg BID or 14 mg extended-release qDay) and donepezil 10 mg/day can be switched to Namzaric 14 mg/10 mg, taken once a day in the evening
Administration
May take with or without food
Capsules can be taken intact or may be opened, sprinkled on applesauce, and swallowed without chewing
The entire contents of each capsule should be consumed; the dose should not be divided
Except when opened and sprinkled on applesauce, the capsule should be swallowed capsule whole; do not divide, chew, or crush
Contra Indications
Hypersensitivity to memantine, donepezil, or piperidine derivatives
Precautions
Memantine
Conditions that raise urine pH may decrease urinary elimination and increase plasma levels of memantine
Use caution in cardiovascular disease, seizure disorder, ophthalmic disease, hepatic and/or renal impairment
Donepezil
Risk of GI bleed, especially in patients with history of gastric ulcer or those at increased risk of developing ulcers
Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia
Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block
May cause diarrhea, nausea, and vomiting
May cause anorexia and/or weight loss (dose dependent)
Cholinomimetics may cause bladder outflow obstructions
Cholinomimetics are believed to have some potential to cause generalized convulsions
Cholinesterase inhibitors should be prescribed with care with history of asthma or obstructive
Pregnancy-Lactation
Pregnancy Category: B (memantine); C (donepezil)
Lactation: Unknown if distributed in human breast milk
Interactions
Adverse Effects
Side effects of Memantine + Donepezil :
>10% (donepezil)
Nausea (5-19%)
Diarrhea (8-15%)
Insomnia (5-14%)
Accident (7-13%)
Infection (11%)
1-10% (memantine)
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%)
1-10% (donepezil)
Headache (4-10%)
Vomiting (3-8%)
Cramping (3-8%)
Fatigue (3-8%)
Anorexia (3-7%)
Hypertension (3% )
Abnormal dreams (3%)
Hallucinations (3%)
Confusion (2%)
Syncope (2%)
Mechanism of Action
Memantine: Low- to moderate-affinity uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist that binds preferentially to NMDAR-operated cation channels, blocking receptor only under conditions of excessive stimulation, with no effect on normal neurotransmission
Donepezil: Acetylcholinesterase inhibitor that causes an increase in concentrations of acetylcholine, which in turn enhances cholinergic neurotransmission