Memantine and donepezil

Name: Memantine and donepezil

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Before Using memantine and donepezil

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For memantine and donepezil, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to memantine and donepezil or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of memantine and donepezil combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of memantine and donepezil combination in the elderly.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking memantine and donepezil, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using memantine and donepezil with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Amifampridine
Amisulpride
Bepridil
Cisapride
Dronedarone
Fluconazole
Ketoconazole
Mesoridazine
Pimozide
Piperaquine
Posaconazole
Saquinavir
Sparfloxacin
Terfenadine
Thioridazine
Ziprasidone

Using memantine and donepezil with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abiraterone
Acetazolamide
Acetophenazine
Aclidinium
Acrivastine
Alcaftadine
Alfentanil
Alfuzosin
Amantadine
Ambenonium
Amdinocillin
Amdinocillin Pivoxil
Amineptine
Aminophylline
Amiodarone
Amitriptyline
Amitriptylinoxide
Amoxapine
Amphetamine
Ampicillin
Anagrelide
Anisotropine
Antazoline
Apomorphine
Aripiprazole
Aripiprazole Lauroxil
Arsenic Trioxide
Asenapine
Astemizole
Atazanavir
Atomoxetine
Atropine
Azatadine
Azelastine
Azithromycin
Azlocillin
Bacampicillin
Baclofen
Bedaquiline
Belladonna Alkaloids
Benperidol
Benzphetamine
Bepotastine
Bornaprine
Brinzolamide
Bromodiphenhydramine
Bromperidol
Brompheniramine
Buclizine
Bupivacaine
Buprenorphine
Bupropion
Buserelin
Butorphanol
Butriptyline
Butylscopolamine
Carbenicillin
Carbinoxamine
Chlorambucil
Chloroquine
Chlorotrianisene
Chlorpheniramine
Chlorphenoxamine
Chlorpromazine
Cimetropium
Cinacalcet
Cinnarizine
Ciprofloxacin
Citalopram
Clarithromycin
Clemastine
Clemizole
Clidinium
Clobazam
Clomipramine
Cloxacillin
Clozapine
Cobicistat
Cocaine
Codeine
Conjugated Estrogens
Crizotinib
Cyclacillin
Cyclizine
Cyclobenzaprine
Cyclopentolate
Cyclosporine
Cyproheptadine
Dabrafenib
Darifenacin
Dasatinib
Degarelix
Delamanid
Demecarium
Desipramine
Deslorelin
Desvenlafaxine
Deutetrabenazine
Dexbrompheniramine
Dexchlorpheniramine
Dextroamphetamine
Dextromethorphan
Dibenzepin
Dicloxacillin
Dicyclomine
Dienestrol
Diethylstilbestrol
Difenoxin
Dihydrocodeine
Dimenhydrinate
Dimethindene
Diphenhydramine
Diphenylpyraline
Disopyramide
Distigmine
Dixyrazine
Dofetilide
Dolasetron
Domperidone
Dorzolamide
Dothiepin
Doxepin
Doxylamine
Droperidol
Duloxetine
Ebastine
Echothiophate
Edrophonium
Efavirenz
Eliglustat
Emedastine
Enflurane
Epinastine
Eribulin
Erythromycin
Escitalopram
Esterified Estrogens
Estradiol
Estramustine
Estriol
Estrone
Estropipate
Ethinyl Estradiol
Ethopropazine
Etravirine
Famotidine
Felbamate
Fentanyl
Fesoterodine
Fingolimod
Flavoxate
Flecainide
Floxacillin
Flunarizine
Fluoxetine
Fluphenazine
Fluvoxamine
Formoterol
Foscarnet
Fosphenytoin
Galantamine
Gatifloxacin
Gemifloxacin
Glycopyrrolate
Gonadorelin
Goserelin
Granisetron
Guanidine
Halofantrine
Haloperidol
Hetacillin
Histrelin
Homatropine
Hydrocodone
Hydromorphone
Hydroquinidine
Hydroxyamphetamine
Hydroxychloroquine
Hyoscyamine
Ibutilide
Iloperidone
Imipramine
Indalpine
Iprindole
Isoflurophate
Isoniazid
Isopropamide
Itraconazole
Ivabradine
Ketamine
Ketotifen
Lapatinib
Leuprolide
Levocabastine
Levofloxacin
Levomilnacipran
Levorphanol
Lidocaine
Lindane
Lisdexamfetamine
Lithium
Lofepramine
Loxapine
Lumefantrine
Mebeverine
Mebhydrolin
Meclizine
Mefenamic Acid
Mefloquine
Melitracen
Melperone
Mepenzolate
Meperidine
Mestranol
Methadone
Methamphetamine
Methantheline
Methazolamide
Methdilazine
Methicillin
Methixene
Methotrimeprazine
Methylphenidate
Metopimazine
Metronidazole
Mezlocillin
Mifepristone
Milnacipran
Mizolastine
Moricizine
Morphine
Moxifloxacin
Nafarelin
Nafcillin
Nalbuphine
Nalidixic Acid
Nefazodone
Nelfinavir
Neostigmine
Niaprazine
Nilotinib
Norfloxacin
Nortriptyline
Octreotide
Ofloxacin
Olanzapine
Olopatadine
Ondansetron
Opipramol
Orphenadrine
Oxacillin
Oxatomide
Oxybutynin
Oxycodone
Oxymorphone
Paliperidone
Panobinostat
Paroxetine
Pasireotide
Pazopanib
Peginterferon Alfa-2b
Penicillin G
Penicillin V
Pentamidine
Pentazocine
Perazine
Periciazine
Perphenazine
Phenindamine
Pheniramine
Phenylpropanolamine
Phenyltoloxamine
Physostigmine
Pimavanserin
Pinaverium
Pipamperone
Piperacillin
Pipotiazine
Pirenzepine
Pitolisant
Pivampicillin
Pizotyline
Polyestradiol Phosphate
Probucol
Procainamide
Procaine
Prochlorperazine
Promazine
Promestriene
Promethazine
Propafenone
Propantheline
Propicillin
Propiverine
Propizepine
Propoxyphene
Protriptyline
Pyrilamine
Quetiapine
Quinestrol
Quinidine
Quinine
Ranolazine
Remifentanil
Ribociclib
Rilpivirine
Risperidone
Ritonavir
Rivastigmine
Scopolamine
Sertindole
Sertraline
Sevoflurane
Sibutramine
Sodium Bicarbonate
Sodium Phosphate
Sodium Phosphate, Dibasic
Sodium Phosphate, Monobasic
Solifenacin
Sorafenib
Sotalol
Succinylcholine
Sufentanil
Sulbenicillin
Sulpiride
Sultamicillin
Sunitinib
Tacrine
Tacrolimus
Tamoxifen
Tapentadol
Telaprevir
Telavancin
Telithromycin
Temocillin
Terbinafine
Tetrabenazine
Theophylline
Thiethylperazine
Thiopropazate
Thioproperazine
Thonzylamine
Tianeptine
Tibolone
Ticarcillin
Timiperone
Tiotropium
Tizanidine
Tolterodine
Toremifene
Tramadol
Trazodone
Trifluoperazine
Triflupromazine
Trimeprazine
Trimipramine
Tripelennamine
Triprolidine
Triptorelin
Tropicamide
Trospium
Umeclidinium
Valethamate
Vandetanib
Vardenafil
Vemurafenib
Venlafaxine
Vilanterol
Vinflunine
Voriconazole
Vorinostat
Zuclopenthixol

Using memantine and donepezil with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Ramelteon

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using memantine and donepezil with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use memantine and donepezil, or give you special instructions about the use of food, alcohol, or tobacco.

Bitter Orange
Grapefruit Juice

If OVERDOSE is suspected

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.

Brand Names U.S.

Namzaric

Storage

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.

Drug Interactions

Alkalinizing Agents: May increase the serum concentration of Memantine. Monitor therapy

Amifampridine: May enhance the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase inhibitor side effects may also be increased. Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Amifampridine. Amifampridine side effects may also be increased. Monitor therapy

Anticholinergic Agents: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Monitor therapy

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

Benoxinate: Acetylcholinesterase Inhibitors may enhance the therapeutic effect of Benoxinate. Specifically, the effects of benoxinate may be prolonged. Monitor therapy

Benperidol: Memantine may diminish the therapeutic effect of Benperidol. Monitor therapy

Beta-Blockers: Acetylcholinesterase Inhibitors may enhance the bradycardic effect of Beta-Blockers. Exceptions: Levobunolol; Metipranolol. Monitor therapy

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

BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy

Carbonic Anhydrase Inhibitors: May increase the serum concentration of Memantine. Exceptions: Brinzolamide; Dorzolamide. 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. Avoid combination

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

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Dipyridamole: May diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Acetylcholinesterase Inhibitors may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy

NMDA Receptor Antagonists: May enhance the adverse/toxic effect of Memantine. 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. 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. Consider therapy modification

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. 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. Monitor therapy

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.

Monitoring Parameters

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

Pregnancy Considerations

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

Patient Education

• 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.