A fixed-dose combination (FDC) of two centrally acting agents with complementary mechanisms for the symptomatic treatment of moderate to severe Alzheimer's disease (AD). Donepezil is a reversible, non-competitive acetylcholinesterase inhibitor (AChEI), while Memantine is a low-to-moderate affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. This combination addresses both cholinergic deficit and glutamatergic excitotoxicity, which are key pathological features of AD. The combination has shown superior efficacy in cognition, global function, and activities of daily living compared to monotherapy in clinical trials, and is a recommended therapeutic strategy in Indian and international guidelines for moderate to severe AD.
Adult: One tablet (Donepezil 5mg + Memantine 5mg) orally once daily, preferably at bedtime. For Donepezil component: After 4-6 weeks, the dose may be increased to Donepezil 10mg + Memantine 5mg or 10mg based on clinical response and tolerability. Titration should be done under physician supervision.
Note: Swallow the tablet whole with water, with or without food. Taking it at bedtime may minimize cholinergic side effects like nausea and 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 dual, complementary action on two major neurotransmitter systems implicated in Alzheimer's disease pathology. Donepezil increases synaptic acetylcholine concentration by inhibiting its breakdown, thereby enhancing cholinergic neurotransmission, which is crucial for memory and learning. Memantine modulates glutamatergic transmission by blocking NMDA receptors. It preferentially blocks pathologically overactivated NMDA receptors (associated with excitotoxicity and neuronal damage) while allowing normal physiological activation required for synaptic plasticity. This reduces glutamate-mediated excitotoxicity and may have neuroprotective effects.
Pregnancy: Category C (US FDA). There are no adequate and well-controlled studies in pregnant women. Donepezil and Memantine cross the placenta in animals. Use only if the potential benefit justifies the potential risk to the fetus. Not indicated for women of childbearing potential.
Driving: May cause dizziness, somnolence, blurred vision, or muscle cramps. Patients should be cautioned about operating machinery or driving until they know how the medication affects them.
| Ketoconazole, Itraconazole, Erythromycin | Increase Donepezil plasma levels via CYP3A4/2D6 inhibition, increasing risk of side effects. | Major |
| Carbamazepine, Phenytoin, Rifampicin | Decrease Donepezil plasma levels via CYP450 induction, reducing efficacy. | Moderate |
| Beta-blockers (e.g., Atenolol), Digoxin, Diltiazem | Potentiate bradycardic effects of Donepezil, risk of syncope and falls. | Major |
| Anticholinergic drugs (e.g., Oxybutynin, Amitriptyline) | Counteract the therapeutic effect of Donepezil. | Moderate |
| Cholinergic agonists (e.g., Bethanechol) | Synergistic effect, risk of excessive cholinergic stimulation. | Major |
| Other NMDA antagonists (e.g., Amantadine, Ketamine) | Additive CNS effects with Memantine; increased risk of psychosis, confusion. | Major |
| Drugs that alkalinize urine (e.g., Carbonic Anhydrase Inhibitors, Sodium Bicarbonate) | Decrease renal elimination of Memantine, increasing its levels and toxicity. | Moderate |
| Diuretics (e.g., Hydrochlorothiazide) | May increase Memantine levels. Risk of hyponatremia. | Moderate |
| Antipsychotics (Typical and Atypical) | May antagonize effects of Donepezil. Increased mortality risk in dementia patients. Use with extreme caution. | Major |