Memantine and donepezil hydrochlorides extended-release capsules are a combination of memantine hydrochloride, an NMDA receptor antagonist, and donepezil hydrochloride, an acetylcholinesterase inhibitor. It is indicated for the treatment of moderate to severe Alzheimer’s type dementia in patients who are stabilized on donepezil hydrochloride 10 mg once daily.

7/10 Capsule: Each extended-release capsule contains Memantine Hydrochloride (as extended-release pellets) 7 mg and Donepezil Hydrochloride (as immediate-release pellets) 10 mg.

14/10 Capsule: Each extended-release capsule contains Memantine Hydrochloride 14 mg and Donepezil Hydrochloride 10 mg.

21/10 Capsule: Each extended-release capsule contains Memantine Hydrochloride 21 mg and Donepezil Hydrochloride 10 mg.

28/10 Capsule: Each extended-release capsule contains Memantine Hydrochloride 28 mg and Donepezil Hydrochloride 10 mg.

Memantine and donepezil hydrochlorides extended-release capsules contain two approved medicines: memantine hydrochloride extended-release and donepezil hydrochloride. Each works through a different mechanism in Alzheimer’s disease.

Memantine: Persistent activation of NMDA receptors in the central nervous system by glutamate is thought to contribute to Alzheimer’s disease symptoms. Memantine exerts its effect as a low to moderate affinity uncompetitive NMDA receptor antagonist, binding preferentially to receptor-operated cation channels. There is no evidence that memantine prevents or slows neurodegeneration in Alzheimer’s disease.

Donepezil: Cognitive symptoms of Alzheimer’s disease are partly attributed to reduced cholinergic neurotransmission. Donepezil enhances cholinergic function by reversibly inhibiting acetylcholinesterase, thereby increasing acetylcholine levels in the brain. There is no evidence that donepezil prevents or slows neurodegeneration.

For patients on donepezil hydrochloride 10 mg only, the recommended starting dose of memantine and donepezil hydrochlorides extended-release capsules is 7 mg/10 mg, taken once daily in the evening. The dose should be increased in 7 mg increments to the recommended maintenance dose of 28 mg/10 mg. The minimum recommended interval between dose increases is one week.

Patients on memantine hydrochloride (10 mg twice daily or 28 mg extended-release once daily) and donepezil hydrochloride 10 mg once daily can be switched to memantine and donepezil hydrochlorides extended- release capsules 28 mg/10 mg, taken once daily in the evening.

Memantine and donepezil hydrochlorides extended- release capsules can be taken with or without food, whole or sprinkled on applesauce; do not divide, chew, or crush. Severe renal impairment: the recommended maintenance dose for memantine and donepezil hydrochlorides extended-release capsules is 14 mg/10 mg once daily in the evening.

Combined use with NMDA antagonists should be approached with caution. Memantine and donepezil hydrochlorides extended-release may interfere with anticholinergic drugs. Concomitant use with succinylcholine, other neuromuscular blocking agents, or cholinergic agonists may produce a synergistic effect.

Memantine and donepezil hydrochlorides extended-release capsules are contraindicated in patients with known hypersensitivity to memantine hydrochloride, donepezil hydrochloride, piperidine derivatives, or any excipients in the formulation.

The most common adverse reactions with memantine hydrochloride extended-release 28 mg/day (≥5% and greater than placebo) include headache, diarrhea, and dizziness. Common adverse reactions with donepezil (≥5% and at least twice placebo rate) include diarrhea, anorexia, vomiting, nausea, and ecchymosis.

There are no adequate data on developmental risk associated with memantine and donepezil hydrochlorides extended-release capsules or their active ingredients in pregnant women. There are also no data on their presence in human milk, their effects on the breastfed infant, or their influence on milk production.

• Memantine and donepezil hydrochlorides extended-release may enhance succinylcholine-type muscle relaxation during anesthesia.
• It may produce vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia or heart block.
• Patients should be monitored for signs of gastrointestinal bleeding, especially those at higher risk of ulcers.
• It may cause diarrhea, nausea, and vomiting.
• It may lead to bladder outflow obstruction.
• Conditions that increase urine pH may reduce the elimination of memantine, resulting in higher plasma levels.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
Renal Impairment: No dose adjustment is required in mild to moderate renal impairment.
Hepatic Impairment: No dose adjustment is required in mild to moderate hepatic impairment. It has not been studied in severe hepatic impairment.

Anti-Alzheimer drugs.

Store below 30°C, protected from light and moisture. Keep out of reach of children.