Memantine and Donepezil (Lexi-Drugs)

Pronunciation

(me MAN teen & doh NEP e zil)

Brand Names: US

Namzaric

Dosing: Adult

Alzheimer dementia (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.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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.

Dosing: Hepatic Impairment: Adult

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).

Use: Labeled Indications

Alzheimer disease (moderate to severe): Treatment of moderate to severe dementia of the Alzheimer type in patients stabilized on donepezil 10 mg once daily.

Clinical Practice Guidelines

American Psychiatric Association, “Treatment of Patients with Alzheimer’s Disease and Other Dementias, Second Edition,” October 2007

“EFNS 2010 Guidelines for the Diagnosis and Management of Alzheimer’s Disease,” March 2010

Administration: 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.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, lack of appetite, muscle cramps, nausea, vomiting, loss of strength and energy, or insomnia. Have patient report immediately to prescriber black, tarry, or bloody stools; difficult urination; severe dizziness; passing out; chills; pharyngitis; difficulty breathing; seizures; severe headache; abdominal pain; heartburn; bradycardia; abnormal heartbeat; bruising; or vomiting blood (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Contraindications

Hypersensitivity to memantine, donepezil, piperidine derivatives, or any component of the formulation

Documentation of allergenic cross-reactivity for cholinesterase inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Warnings/Precautions

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.

• 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. Alzheimer treatment guidelines consider bradycardia to be a relative contraindication for use of centrally active cholinesterase inhibitors (APA [Rabins 2007].

• Peptic ulcer disease: Use with caution in patients at risk of ulcer disease (eg, previous history or NSAID 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 COPD 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]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Geriatric Considerations

See individual agents.

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. See individual agents.

Breast-Feeding Considerations

It is not known if donepezil or memantine are excreted 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.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

See individual agents.

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions 

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: Acetylcholinesterase Inhibitors (Central) may enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. 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. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Risk C: Monitor therapy

Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Exceptions: Brinzolamide; Dorzolamide. 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. Exceptions are discussed in separate monographs. Risk D: Consider therapy modification

Cholinergic Agonists: Acetylcholinesterase Inhibitors may enhance the adverse/toxic effect of Cholinergic Agonists. 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

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

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Risk C: Monitor therapy

Succinylcholine: Acetylcholinesterase Inhibitors may increase the serum concentration of Succinylcholine. Management: Consider alternatives to this combination due to a risk of prolonged neuromuscular blockade. Risk D: Consider therapy modification

Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate’s labeling. Risk D: Consider therapy modification

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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. Memantine may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy

Monitoring Parameters

Mental status; general function (eg, activities of daily living); symptoms of active or occult GI bleeding; symptoms of GI intolerance

Advanced Practitioners Physical Assessment/Monitoring

Assess stage of Alzheimer’s disease and mental status prior to initiation. Assess bladder adequacy prior to treatment. Assess for cholinergic crisis. Monitor pulse.

Nursing Physical Assessment/Monitoring

Monitor for cholinergic crisis (DUMBELS – diarrhea, urination, miosis, bronchospasm/bradycardia, excitability, lacrimation, and salivation/excessive sweating). Monitor pulse. Monitor for disease progression.

Dosage Forms: US

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 brilliant blue fcf (fd&c blue #1), corn starch, fd&c yellow #6 (sunset yellow)]

Capsule Extended Release 24 Hour, Oral:

Namzaric: Memantine hydrochloride 14 mg and donepezil hydrochloride 10 mg [contains brilliant blue fcf (fd&c blue #1)]

Namzaric: Memantine hydrochloride 28 mg and donepezil hydrochloride 10 mg [contains brilliant blue fcf (fd&c blue #1), corn starch]

Namzaric: Memantine hydrochloride 7 mg and donepezil hydrochloride 10 mg [contains brilliant blue fcf (fd&c blue #1), corn starch, 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)]

Anatomic Therapeutic Chemical (ATC) Classification
  • N06DA52
Generic Available (US)

No

Pricing: US

Capsule ER 24 Hour Therapy Pack (Namzaric Oral)

7-10 mg (per each): $18.51

7 & 14 & 21 &28-10 MG (per each): $18.51

14-10 mg (per each): $18.51

21-10 mg (per each): $18.51

28-10 mg (per each): $18.51

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.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

See individual agents.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Index Terms

Donepezil Hydrochloride and Memantine Hydrochloride; Memantine HCl/Donepezil HCl; Namzaric

FDA Approval Date
December 23, 2014
References

Matsumoto T, Kawanishi C, Isojima D, et al. Neuroleptic malignant syndrome induced by donepezil. Int J Neuropsychopharmacol. 2004;7(1):101-103.[PubMed 14731314]

Namzaric (memantine and donepezil) [prescribing information]. Madison, NJ: Allergan USA, Inc; January 2019.

Rabins PV, Blacker D, Rovner BW, et al; APA Work Group on Alzheimer’s Disease and other Dementias. American Psychiatric Association practice guideline for the treatment of patients with Alzheimer’s disease and other dementias. Second edition. Am J Psychiatry. 2007;164(12 suppl):5-56.[PubMed 18340692]

Sahin OZ, Ayaz T, Yuce S, et al. A rare case of acute renal failure secondary to rhabdomyolysis probably induced by donepezil [published online April 27, 2014]. Case Rep Nephrol. 2014;2014:214359. doi: 10.1155/2014/214359.[PubMed 24864216]

Warwick TC, Moningi V, Jami P, et al. Neuroleptic malignant syndrome variant in a patient receiving donepezil and olanzapine [published online January 22, 2008]. Nat Clin Pract Neurol. 2008;4(3):170-174. doi: 10.1038/ncpneuro0728.[PubMed 18212788]

Brand Names: International

Alzil-M (IN); Carrier Plus (AR); Depzil Plus (IN); Neuroplus Dual (AR); Tonibral MD (AR); Valpex Duo (AR)

Memantine and Donepezil (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(me MAN teen & doh NEP e zil)

Brand Names: US

Namzaric

What is this drug used for?
  • It is used to treat dementia in people with Alzheimer’s disease.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to this drug or any part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • This drug may interact with other drugs or health problems.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists.
  • This drug is not a cure for Alzheimer’s disease. Stay under the care of your doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Trouble passing urine.
  • Very bad dizziness or passing out.
  • Fever or chills.
  • Sore throat.
  • Trouble breathing that is new or worse.
  • Seizures.
  • Very bad headache.
  • Belly pain or heartburn.
  • Black, tarry, or bloody stools.
  • Throwing up blood or throw up that looks like coffee grounds.
  • Slow heartbeat.
  • A heartbeat that does not feel normal.
  • Bruising.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
  • Diarrhea.
  • Upset stomach or throwing up.
  • Not hungry.
  • Dizziness.
  • Headache.
  • Muscle cramps.
  • Feeling tired or weak.
  • Not able to sleep.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Take in the evening.
  • Take with or without food.
  • Swallow whole. Do not chew or crush.
  • Do not take any capsules that do not look normal or are damaged.
  • If you cannot swallow this drug whole, you may sprinkle the contents on applesauce. If you do this, swallow the mixture right away without chewing.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
  • Skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in the original container or in another container that protects this drug from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.