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

Side 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%)

Mode 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