A fixed-dose combination (FDC) therapy for moderate to severe Alzheimer's disease. Donepezil is a centrally acting, reversible acetylcholinesterase inhibitor, while Memantine is a low-affinity, voltage-dependent, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. This combination provides dual neurochemical modulation, addressing both cholinergic deficit and glutamatergic excitotoxicity, which are key pathological features of Alzheimer's disease. It is a cornerstone of symptomatic management in the Indian context, aiming to improve cognition, function, and behavior.
Adult: One tablet (Donepezil 5mg + Memantine 10mg) orally once daily, preferably at bedtime. For initiation in patients new to memantine, a titration schedule is recommended (start with memantine 5mg alone, then increase to 10mg, then switch to this FDC).
Note: Administer orally, with or without food. Swallow whole with a glass of water. Bedtime administration may improve tolerability of initial cholinergic side effects (like nausea, diarrhea). Do not crush or chew. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not double the dose.
The combination exerts a synergistic effect by targeting two distinct pathological pathways in Alzheimer's disease. Donepezil increases acetylcholine concentration in the synaptic cleft by inhibiting its breakdown, thereby enhancing cholinergic neurotransmission, which is crucial for memory and learning. Memantine modulates glutamatergic transmission by blocking NMDA receptors, preventing pathological, chronic calcium influx into neurons (excitotoxicity) while allowing physiological, transient activation required for normal synaptic plasticity.
Pregnancy: Category C (US FDA). Donepezil and Memantine. Animal studies have shown adverse effects. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus. Not indicated for this population.
Driving: May cause dizziness, somnolence, and blurred vision. Patients should be cautioned about operating machinery or driving until they are certain the medication does not affect them adversely.
| Ketoconazole, Itraconazole, Erythromycin | Inhibit CYP3A4, increasing Donepezil plasma levels, risk of toxicity. | Major |
| Rifampicin, Carbamazepine, Phenytoin | Induce CYP3A4, decreasing Donepezil plasma levels, reducing efficacy. | Major |
| Paroxetine, Fluoxetine (Strong CYP2D6 inhibitors) | Increase Donepezil plasma levels. | Moderate |
| Cholinergic agents (Bethanechol, Pilocarpine) | Additive cholinergic effects, risk of syncope, bradycardia. | Major |
| Anticholinergic agents (Oxybutynin, Tolterodine, Tricyclic Antidepressants) | Antagonize Donepezil's therapeutic effect. | Moderate |
| Succinylcholine, similar neuromuscular blocking agents | Donepezil may prolong muscle paralysis. | Major |
| Hydrochlorothiazide, Cimetidine, Ranitidine, Quinidine | Alkalinize urine, reducing renal excretion of Memantine, increasing levels. | Moderate |
| Other NMDA antagonists (Amantadine, Dextromethorphan, Ketamine) | Additive CNS effects, risk of psychosis, confusion. | Major |
| Beta-blockers, Digoxin, Diltiazem, Verapamil | Increased risk of bradycardia and heart block with Donepezil. | Major |
Same composition (Donepezil (5mg) + Memantine (10mg)), different brands: