Dosing and uses of Namzaric (memantine/donepezil)
Adult dosage forms and strengths
memantine extended-release/donepeziL
capsule
- 7mg/10mg
- 14mg/10mg
- 21mg/10mg
- 28mg/10mg
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
Stabilized on donepezil and not currently on memantine
- Starting dose is 7 mg/10 mg PO, taken once a day in the evening
- Increase dose in 7 mg increments based on the memantine component to the recommended maintenance dose of 28 mg/10 mg once daily
- The minimum recommended interval between dose increases is 1 week
- Only increase if the previous dose is well tolerated
- Maximum dose: 28 mg/10 mg qDay
Stabilized on both donepezil and memantine
- Patients on memantine (10 mg BID or 28 mg extended-release qDay) and donepezil 10 mg/day can be switched to Namzaric 28 mg/10 mg PO, taken once a day in the evening
- Initiate the day following the last dose of memantine and donepezil administered separately
Dosage modifications
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
Pediatric dosage forms and strengths
Not indicated
Namzaric (memantine/donepezil) adverse (side) effects
>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%)
Warnings
Contraindications
Hypersensitivity to memantine, donepezil, or piperidine derivatives
Cautions
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 and lactation
Pregnancy category: B (memantine); C (donepezil)
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Namzaric (memantine/donepezil)
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
Absorption
Peak plasma time (memantine ER): 18 hr (with food); 25 hr (fasting)
Distribution
Protein bound (memantine ER): 45%
Vd (memantine ER): 9-11 L/kg
Metabolism
Memantine: Undergoes partial hepatic metabolism; CYP450 enzyme system does not play a significant role
Elimination
Half-life (memantine): 60-80 hr
Excretion (memantine): Predominantly in urine (48% unchanged); renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption
Administration
Oral 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
