Version May 2024
Alzheimer disease (moderate to severe):
Oral:
Patients stabilized on donepezil 10 mg once daily and not currently on memantine: Initial: Memantine extended release (ER) 7 mg/donepezil 10 mg once daily in the evening. Increase dose in increments of memantine ER 7 mg at intervals of ≥1 week to maintenance dose of memantine ER 28 mg/donepezil 10 mg once daily based on patient response and tolerability. Maximum dose: memantine ER 28 mg/ donepezil 10 mg once daily.
Patients stabilized on memantine (10 mg twice daily or 28 mg ER once daily) and donepezil 10 mg: Initial: Memantine ER 28 mg/donepezil 10 mg once daily in the evening. Initiate combination therapy the day after the last dose of memantine and donepezil administered separately.
Discontinuation of therapy: Discontinuation of therapy may result in worsening of cognitive function (Howard 2012). Avoid abrupt discontinuation except in the case of severe adverse drug reaction to minimize withdrawal symptoms (eg, altered mental status, hallucinations, delusions, insomnia, increased anxiety and agitation). In general, cholinesterase inhibitors and memantine should be tapered using a 50% dose reduction or stepwise reduction via available dose formulations every 4 weeks to the lowest dose prior to discontinuation. Consider re-initiation if clear worsening of the condition occurs after withdrawal (Reeve 2019).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to moderate impairment (CrCl 30 to 80 mL/minute): No dosage adjustment necessary.
Severe renal impairment (CrCl 5 to 29 mL/minute):
Patients stabilized on donepezil 10 mg once daily and not currently on memantine: Initial: Memantine ER 7 mg/donepezil 10 mg once daily in the evening. Increase dose in increments of memantine ER 7 mg at intervals of ≥1 week to maintenance dose of memantine ER 14 mg/donepezil 10 mg once daily.
Patients stabilized on memantine (5 mg twice daily or 14 mg ER once daily) and donepezil 10 mg: May switch patients to memantine ER 14 mg/donepezil 10 mg once daily.
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Refer to adult dosing.
See individual agents.
Hypersensitivity to memantine, donepezil, piperidine derivatives, or any component of the formulation
Concerns related to adverse effects:
• Cardiovascular effects: Cholinesterase inhibitors may have vagotonic effects which may cause bradycardia and/or heart block with or without a history of cardiac disease; syncopal episodes have been associated with donepezil. Long-term use (eg, ≥1 year) may cause QT interval prolongation (Kho 2021).
• GI effects: May cause dose-related diarrhea, nausea, and/or vomiting; usually resolves in 1 to 3 weeks.
• Neuroleptic malignant syndrome: Rare cases of neuroleptic malignant syndrome (NMS) have been reported (Matsumoto 2004; Warwick 2008). Discontinuation of donepezil therapy may be necessary in patients presenting with symptoms of NMS (eg, hyperthermia, irregular pulse or blood pressure, cardiac arrhythmia, diaphoresis, muscle rigidity, mental status changes, elevated creatine phosphokinase [CPK], unexplained high fever without additional symptoms).
• Rhabdomyolysis: Rare cases of rhabdomyolysis (including acute renal failure) have been reported after a few months of therapy (Sahin 2014) or in the days following therapy initiation and dose increase (Aricept Canadian product monograph 2014). Use with caution in patients with risk factors for rhabdomyolysis (eg, concomitant medications associated with rhabdomyolysis, history of muscular disorders, uncontrolled hypothyroidism, renal/hepatic impairment). Discontinuation of therapy may be necessary for marked elevation of CPK levels and/or symptoms (eg, muscle pain, tenderness or weakness, malaise, fever, dark urine) suggesting rhabdomyolysis.
Disease-related concerns:
• Cardiac conduction abnormalities: Use with caution in patients with sick-sinus syndrome, bradycardia, or conduction abnormalities.
• Ophthalmic disease: Worsening of corneal condition has been observed in a clinical trial with memantine. Reversible corneal endothelial dysfunction may occur (Feng 2015).
• Peptic ulcer disease: Use with caution in patients at risk of ulcer disease (eg, previous history of ulcer disease or concomitant nonsteroidal anti-inflammatory drug use); cholinesterase inhibitors may increase gastric acid secretion. Monitor for symptoms of bleeding.
• Renal impairment: Use caution in patients with renal impairment; reduce dose in patients with severe renal impairment.
• Respiratory disease: Use with caution in patients with chronic obstructive pulmonary disease and/or asthma.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; cholinomimetics may potentially cause generalized seizures, although seizure activity may also result from Alzheimer disease.
• Urinary tract obstruction: Use with caution in patients with bladder outlet obstruction or prostatic hyperplasia; cholinomimetics may cause or worsen outflow obstructions, including possible exacerbation of BPH symptoms (APA [Rabins 2007]).
Other warnings/precautions:
• Urine pH: Clearance is significantly reduced by alkaline urine; use caution with medications, dietary changes, or patient conditions which may alter urine pH.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule ER 24 Hour Therapy Pack, Oral:
Namzaric: Memantine hydrochloride 7 mg and donepezil hydrochloride 10 mg (7s) & memantine hydrochloride 14 mg and donepezil hydrochloride 10 mg (7s) & memantine hydrochloride 21 mg and donepezil hydrochloride 10 mg (7s) & memantine hydrochloride 28 mg and donepezil hydrochloride 10 mg (7s) (28 ea) [contains corn starch, fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Capsule Extended Release 24 Hour, Oral:
Namzaric: Memantine hydrochloride 28 mg and donepezil hydrochloride 10 mg [contains corn starch, fd&c blue #1 (brilliant blue)]
Namzaric: Memantine hydrochloride 7 mg and donepezil hydrochloride 10 mg [contains corn starch, fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Namzaric: Memantine hydrochloride 21 mg and donepezil hydrochloride 10 mg [contains corn starch, fd&c yellow #6 (sunset yellow)]
Namzaric: Memantine hydrochloride 14 mg and donepezil hydrochloride 10 mg [contains fd&c blue #1 (brilliant blue)]
No
Capsule ER 24 Hour Therapy Pack (Namzaric Oral)
7-10 mg (per each): $23.62
7 & 14 & 21 &28-10 MG (per each): $23.62
14-10 mg (per each): $23.62
21-10 mg (per each): $23.62
28-10 mg (per each): $23.62
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer in the evening without regard to meals. Swallow capsule whole; do not divide, chew, or crush. May open capsule and sprinkle entire contents on applesauce; swallow immediately. Do not divide contents of capsule into separate doses.
Alzheimer disease (moderate to severe): Treatment of moderate to severe Alzheimer disease in patients stabilized on donepezil 10 mg once daily.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alkalinizing Agents: May increase the serum concentration of Memantine. Risk C: Monitor therapy
Amifampridine: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Amifampridine may enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Risk C: Monitor therapy
Anticholinergic Agents: Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Antipsychotic Agents: Donepezil may enhance the neurotoxic (central) effect of Antipsychotic Agents. Risk C: Monitor therapy
Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Risk C: Monitor therapy
Benperidol: Memantine may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy
Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Risk C: Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification
Chlorprothixene: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Chlorprothixene. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Chlorprothixene. Risk C: Monitor therapy
Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. Specifically, cholinergic effects may be enhanced or increased. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Risk C: Monitor therapy
Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination
Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy
Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
NMDA Receptor Antagonists: May enhance the adverse/toxic effect of Memantine. Risk C: Monitor therapy
Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification
Succinylcholine: Acetylcholinesterase Inhibitors may enhance the neuromuscular-blocking effect of Succinylcholine. Risk C: Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy
Trimethoprim: May enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Risk C: Monitor therapy
Adverse events have been observed in some animal reproduction studies. See individual monographs for additional information.
It is not known if donepezil or memantine are present in breast milk. According to the manufacturer, the decision to breast-feed during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother. See individual agents.
Cognitive function; symptoms of active or occult GI bleeding; symptoms of GI intolerance; weight.
Memantine: Glutamate, the primary excitatory amino acid in the CNS, may contribute to the pathogenesis of Alzheimer disease (AD) by overstimulating various glutamate receptors leading to excitotoxicity and neuronal cell death. Memantine is an uncompetitive antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors, located ubiquitously throughout the brain. Under normal physiologic conditions, the (unstimulated) NMDA receptor ion channel is blocked by magnesium ions, which are displaced after agonist-induced depolarization. Pathologic or excessive receptor activation, as postulated to occur during AD, prevents magnesium from reentering and blocking the channel pore resulting in a chronically open state and excessive calcium influx. Memantine binds to the intra-pore magnesium site, but with longer dwell time, and thus functions as an effective receptor blocker only under conditions of excessive stimulation; memantine does not affect normal neurotransmission.
Donepezil: Alzheimer disease is characterized by cholinergic deficiency in the cortex and basal forebrain, which contributes to cognitive deficits. Donepezil reversibly and noncompetitively inhibits centrally-active acetylcholinesterase, the enzyme responsible for hydrolysis of acetylcholine. This appears to result in increased concentrations of acetylcholine available for synaptic transmission in the central nervous system.
See individual agents.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
