Section 05 · Monograph

Memantine-donepezil

Reviewed Nov 2026FDA label

NamzaricNMDA antagonist + AChE inhibitor

Indications

Treatment of moderate to severe dementia of the Alzheimer's type in patients already stabilized on donepezil hydrochloride 10 mg once dailyFDA-labeled

Fixed-dose combination pairing two complementary, independent mechanisms: donepezil (reversible acetylcholinesterase inhibitor) and memantine (uncompetitive NMDA receptor antagonist)
Intended for patients with moderate-to-severe disease already tolerating donepezil monotherapy, adding memantine's distinct mechanism
No clinically significant pharmacokinetic interaction between the memantine and donepezil components at therapeutic doses

Available as extended-release capsules combining memantine ER 7, 14, 21, or 28 mg with donepezil 10 mg
Only initiate in patients already established and stable on donepezil 10 mg once daily
If not currently taking memantine: start memantine 7 mg/donepezil 10 mg once daily in the evening, then increase the memantine component by 7 mg at intervals of at least 1 week to the target maintenance dose of 28 mg/10 mg once daily
If already taking memantine (IR or XR) plus donepezil 10 mg: switch directly to the strength containing the corresponding total daily memantine dose paired with 10 mg donepezil
Capsules may be swallowed whole or opened and sprinkled on applesauce; beads should not be divided, chewed, or crushed

Severe renal impairment (CrCl 5-29 mL/min): target maintenance dose is 14 mg/10 mg once daily

Known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or any formulation excipients

CYP2D6/CYP3A4 inhibitors (ketoconazole, quinidine, erythromycin) may increase exposure to the donepezil component
Drugs that alkalinize urine reduce renal clearance of the memantine component, risking accumulation
Anticholinergic drugs may antagonize the cholinergic effect of the donepezil component
Succinylcholine: exaggerated muscle relaxation possible via the donepezil component during anesthesia
Other NMDA antagonists (amantadine, ketamine, dextromethorphan): use with caution due to the memantine component

Cardiac conduction status (bradycardia/AV block risk from donepezil component); baseline ECG in at-risk patients
Signs/symptoms of GI bleeding, especially with concurrent NSAID use
Weight and nutritional status
Renal function, which governs dosing of the memantine component
Cognitive and functional status periodically
Dizziness, confusion, and fall risk, particularly during titration

No adequate, well-controlled human pregnancy data for the fixed-dose combination
Component data show developmental toxicity in animal studies only at maternally toxic dose levels
Alzheimer's disease predominantly affects postmenopausal women; use during pregnancy only if potential benefit justifies fetal risk
Unknown whether either component is excreted in human milk; use during breastfeeding not recommended given lack of data