memantine/donepezil (Rx)

Brand and Other Names:Namzaric

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

memantine/donepezil

capsule ER

  • 7mg/10mg
  • 14mg/10mg
  • 21mg/10mg
  • 28mg/10mg

Alzheimer Disease

Fixed dose combination product for patients with moderate-to-severe Alzheimer disease currently stabilized on donepezil 10 mg once daily

Recommended dose is 28 mg/10 mg PO qDay

Stabilized on donepezil and not currently on memantine

  • Starting dose is 7 mg/10 mg PO, taken once a day in the evening
  • Increase dose in 7 mg increments based on the memantine component to the recommended maintenance dose of 28 mg/10 mg once daily
  • The minimum recommended interval between dose increases is 1 week
  • Only increase if the previous dose is well tolerated
  • Maximum dose: 28 mg/10 mg qDay

Stabilized on both donepezil and memantine

  • Patients on memantine (10 mg BID or 28 mg extended-release qDay) and donepezil 10 mg/day can be switched to Namzaric 28 mg/10 mg PO, taken once a day in the evening
  • Initiate the day following the last dose of memantine and donepezil administered separately

Dosage Modifications

Severe renal impairment

  • Severe renal impairment (CrCl 5-29 mL/min, based on the Cockcroft-Gault equation)
  • Stabilized on donepezil 10 mg/day and not currently on memantine
    • Recommended starting dose: 7 mg/10 mg PO taken once daily in the evening
    • The dose should be increased to the recommended maintenance dose of 14 mg/10 mg once daily in the evening after a minimum of 1 week
  • Stabilized on both donepezil and memantine
    • Patients on memantine (5 mg BID or 14 mg extended-release qDay) and donepezil 10 mg/day can be switched to Namzaric 14 mg/10 mg, taken once a day in the evening

Not indicated

Next:

Interactions

Interaction Checker

and memantine/donepezil

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            Contraindicated (2)

            • dronedarone

              donepezil and dronedarone both increase QTc interval. Contraindicated.

            • thioridazine

              donepezil and thioridazine both increase QTc interval. Contraindicated.

            Serious - Use Alternative (86)

            • amiodarone

              donepezil and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amisulpride

              donepezil and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

            • amoxapine

              donepezil and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

            • anagrelide

              donepezil and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.

            • arsenic trioxide

              donepezil and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              donepezil and artemether both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              donepezil and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine

              donepezil and asenapine both increase QTc interval. Avoid or Use Alternate Drug.

            • asenapine transdermal

              asenapine transdermal and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • azithromycin

              donepezil and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • bedaquiline

              donepezil and bedaquiline both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine

              donepezil and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine buccal

              buprenorphine buccal and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine subdermal implant

              buprenorphine subdermal implant and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine transdermal

              buprenorphine transdermal and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • ceritinib

              donepezil and ceritinib both increase QTc interval. Avoid or Use Alternate Drug.

            • chloroquine

              donepezil and chloroquine both increase QTc interval. Avoid or Use Alternate Drug.

            • chlorpromazine

              donepezil and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              donepezil and citalopram both increase QTc interval. Avoid or Use Alternate Drug.

            • clarithromycin

              donepezil and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • crizotinib

              donepezil and crizotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • dextromethorphan

              memantine, dextromethorphan. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • disopyramide

              donepezil and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

            • dofetilide

              donepezil and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

            • droperidol

              donepezil and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • encorafenib

              donepezil and encorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • entrectinib

              donepezil and entrectinib both increase QTc interval. Avoid or Use Alternate Drug.

            • eribulin

              donepezil and eribulin both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin base

              donepezil and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              donepezil and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              donepezil and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              donepezil and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole and donepezil both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

            • flecainide

              donepezil and flecainide both increase QTc interval. Avoid or Use Alternate Drug.

            • foscarnet

              donepezil and foscarnet both increase QTc interval. Avoid or Use Alternate Drug.

            • glasdegib

              donepezil and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.

            • histrelin

              donepezil and histrelin both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              donepezil and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.

            • ibutilide

              donepezil and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

            • iloperidone

              donepezil and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • inotuzumab

              donepezil and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.

            • isoflurane

              donepezil and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • ivosidenib

              donepezil and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

            • ketamine

              memantine, ketamine. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated.

            • lefamulin

              lefamulin and donepezil both increase QTc interval. Avoid or Use Alternate Drug.

            • lenvatinib

              donepezil and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • lithium

              donepezil and lithium both increase QTc interval. Avoid or Use Alternate Drug.

            • lofexidine

              donepezil and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.

            • lopinavir

              donepezil and lopinavir both increase QTc interval. Avoid or Use Alternate Drug.

            • macimorelin

              donepezil and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.

            • methadone

              donepezil and methadone both increase QTc interval. Avoid or Use Alternate Drug.

            • midostaurin

              donepezil and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.

            • mobocertinib

              donepezil and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.

            • moxifloxacin

              donepezil and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • nilotinib

              donepezil and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • ondansetron

              donepezil and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.

            • osimertinib

              donepezil and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.

            • oxaliplatin

              donepezil and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.

            • ozanimod

              donepezil and ozanimod both increase QTc interval. Avoid or Use Alternate Drug.

            • paliperidone

              donepezil and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.

            • pazopanib

              donepezil and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.

            • pentamidine

              donepezil and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.

            • pimavanserin

              donepezil and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.

            • pimozide

              donepezil and pimozide both increase QTc interval. Contraindicated.

            • pitolisant

              donepezil and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.

            • ponesimod

              ponesimod, donepezil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.

              donepezil and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.

            • procainamide

              donepezil and procainamide both increase QTc interval. Avoid or Use Alternate Drug.

            • propafenone

              donepezil and propafenone both increase QTc interval. Avoid or Use Alternate Drug.

            • quetiapine

              donepezil and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.

            • quinidine

              donepezil and quinidine both increase QTc interval. Contraindicated.

            • quinine

              donepezil and quinine both increase QTc interval. Avoid or Use Alternate Drug.

            • ribociclib

              ribociclib will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              donepezil and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.

            • selpercatinib

              donepezil and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.

            • sevoflurane

              donepezil and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.

            • siponimod

              donepezil and siponimod both increase QTc interval. Avoid or Use Alternate Drug.

            • solifenacin

              donepezil and solifenacin both increase QTc interval. Avoid or Use Alternate Drug.

            • sorafenib

              donepezil and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.

            • sotalol

              donepezil and sotalol both increase QTc interval. Avoid or Use Alternate Drug.

            • tafenoquine

              tafenoquine will increase the level or effect of memantine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

            • tetrabenazine

              donepezil and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.

            • toremifene

              donepezil and toremifene both increase QTc interval. Avoid or Use Alternate Drug.

            • trazodone

              donepezil and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

            • triamcinolone acetonide injectable suspension

              triamcinolone acetonide injectable suspension, donepezil. unspecified interaction mechanism. Avoid or Use Alternate Drug. Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase agents at least 24 hours before initiating corticosteroid therapy.

            • trilaciclib

              trilaciclib will decrease the level or effect of memantine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

            • trimipramine

              donepezil and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (167)

            • acetazolamide

              acetazolamide will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • aclidinium

              donepezil increases and aclidinium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • albuterol

              donepezil and albuterol both increase QTc interval. Use Caution/Monitor.

            • alfuzosin

              donepezil and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • aluminum hydroxide

              aluminum hydroxide will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • amantadine

              memantine, amantadine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Combination may lead to additive adverse effects. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.

            • amifampridine

              amifampridine and donepezil both increase cholinergic effects/transmission. Use Caution/Monitor.

            • amiodarone

              amiodarone will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • amitriptyline

              donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

              donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • amoxapine

              donepezil increases and amoxapine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • anticholinergic/sedative combos

              donepezil increases and anticholinergic/sedative combos decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • apomorphine

              donepezil and apomorphine both increase QTc interval. Use Caution/Monitor.

            • arformoterol

              donepezil and arformoterol both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

              donepezil and aripiprazole both increase QTc interval. Use Caution/Monitor.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • atomoxetine

              donepezil and atomoxetine both increase QTc interval. Use Caution/Monitor.

            • atracurium

              donepezil increases and atracurium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atropine

              donepezil increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atropine IV/IM

              donepezil increases and atropine IV/IM decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • belladonna alkaloids

              donepezil increases and belladonna alkaloids decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • belladonna and opium

              donepezil increases and belladonna and opium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benztropine

              donepezil decreases effects of benztropine by pharmacodynamic antagonism. Use Caution/Monitor.

            • bethanechol

              bethanechol and donepezil both increase cholinergic effects/transmission. Use Caution/Monitor.

            • calcium carbonate

              calcium carbonate will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • carbachol

              carbachol and donepezil both increase cholinergic effects/transmission. Use Caution/Monitor.

            • carbamazepine

              carbamazepine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cevimeline

              cevimeline and donepezil both increase cholinergic effects/transmission. Use Caution/Monitor.

            • cimetidine

              cimetidine will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

              cimetidine will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ciprofloxacin

              donepezil and ciprofloxacin both increase QTc interval. Use Caution/Monitor.

            • digoxin

              digoxin will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • cisapride

              donepezil and cisapride both increase QTc interval. Use Caution/Monitor.

            • cisatracurium

              donepezil increases and cisatracurium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clomipramine

              donepezil increases and clomipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and clomipramine both increase QTc interval. Use Caution/Monitor.

            • clozapine

              donepezil and clozapine both increase QTc interval. Use Caution/Monitor.

            • cyclizine

              donepezil increases and cyclizine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cyclobenzaprine

              donepezil increases and cyclobenzaprine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • darifenacin

              donepezil increases and darifenacin decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dasatinib

              donepezil and dasatinib both increase QTc interval. Use Caution/Monitor.

            • degarelix

              donepezil and degarelix both increase QTc interval. Use Caution/Monitor.

            • desipramine

              donepezil and desipramine both increase QTc interval. Use Caution/Monitor.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • deutetrabenazine

              donepezil and deutetrabenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

            • dichlorphenamide

              dichlorphenamide and donepezil both decrease serum potassium. Use Caution/Monitor.

            • dicyclomine

              donepezil increases and dicyclomine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diphenhydramine

              donepezil increases and diphenhydramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dofetilide

              dofetilide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • dolasetron

              donepezil and dolasetron both increase QTc interval. Use Caution/Monitor.

            • dosulepin

              donepezil increases and dosulepin decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • doxepin

              donepezil increases and doxepin decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and doxepin both increase QTc interval. Use Caution/Monitor.

            • echothiophate iodide

              donepezil and echothiophate iodide both increase cholinergic effects/transmission. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eliglustat

              donepezil and eliglustat both increase QTc interval. Use Caution/Monitor.

            • erdafitinib

              memantine increases levels of erdafitinib by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

            • erythromycin base

              erythromycin base will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • escitalopram

              donepezil and escitalopram both increase QTc interval. Use Caution/Monitor.

            • fesoterodine

              donepezil increases and fesoterodine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fingolimod

              fingolimod and donepezil both increase QTc interval. Use Caution/Monitor.

            • flavoxate

              donepezil increases and flavoxate decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fluconazole

              donepezil and fluconazole both increase QTc interval. Use Caution/Monitor.

            • fluoxetine

              fluoxetine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              donepezil and fluoxetine both increase QTc interval. Use Caution/Monitor.

            • fluphenazine

              donepezil and fluphenazine both increase QTc interval. Use Caution/Monitor.

            • fluvoxamine

              donepezil and fluvoxamine both increase QTc interval. Use Caution/Monitor.

            • formoterol

              donepezil and formoterol both increase QTc interval. Use Caution/Monitor.

            • fostemsavir

              donepezil and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • galantamine

              donepezil and galantamine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • gemifloxacin

              donepezil and gemifloxacin both increase QTc interval. Use Caution/Monitor.

            • gemtuzumab

              donepezil and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

              donepezil and gilteritinib both increase QTc interval. Use Caution/Monitor.

            • glycopyrrolate

              donepezil increases and glycopyrrolate decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • glycopyrrolate inhaled

              donepezil increases and glycopyrrolate inhaled decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • goserelin

              donepezil and goserelin both increase QTc interval. Use Caution/Monitor.

            • granisetron

              donepezil and granisetron both increase QTc interval. Use Caution/Monitor.

            • haloperidol

              donepezil and haloperidol both increase QTc interval. Use Caution/Monitor.

            • henbane

              donepezil increases and henbane decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • homatropine

              donepezil increases and homatropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • huperzine A

              donepezil and huperzine A both increase cholinergic effects/transmission. Use Caution/Monitor.

            • hydroxyzine

              donepezil and hydroxyzine both increase QTc interval. Use Caution/Monitor.

            • hyoscyamine

              donepezil increases and hyoscyamine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hyoscyamine spray

              donepezil increases and hyoscyamine spray decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • imipramine

              donepezil increases and imipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and imipramine both increase QTc interval. Use Caution/Monitor.

            • indacaterol, inhaled

              donepezil and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.

            • ipratropium

              donepezil increases and ipratropium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • itraconazole

              donepezil and itraconazole both increase QTc interval. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lapatinib

              donepezil and lapatinib both increase QTc interval. Use Caution/Monitor.

            • letermovir

              letermovir increases levels of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • leuprolide

              donepezil and leuprolide both increase QTc interval. Use Caution/Monitor.

            • levalbuterol

              donepezil and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levofloxacin

              donepezil and levofloxacin both increase QTc interval. Use Caution/Monitor.

            • levoketoconazole

              levoketoconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lofepramine

              donepezil increases and lofepramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • loperamide

              donepezil and loperamide both increase QTc interval. Use Caution/Monitor.

            • lumefantrine

              lumefantrine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • maprotiline

              donepezil increases and maprotiline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and maprotiline both increase QTc interval. Use Caution/Monitor.

            • meclizine

              donepezil increases and meclizine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mefloquine

              donepezil and mefloquine both increase QTc interval. Use Caution/Monitor.

            • methscopolamine

              donepezil increases and methscopolamine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mifepristone

              donepezil and mifepristone both increase QTc interval. Use Caution/Monitor.

            • mirtazapine

              donepezil and mirtazapine both increase QTc interval. Use Caution/Monitor.

            • neostigmine

              donepezil and neostigmine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • nortriptyline

              donepezil increases and nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and nortriptyline both increase QTc interval. Use Caution/Monitor.

            • octreotide

              donepezil and octreotide both increase QTc interval. Use Caution/Monitor.

            • ofloxacin

              donepezil and ofloxacin both increase QTc interval. Use Caution/Monitor.

            • olanzapine

              donepezil and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • olodaterol inhaled

              donepezil and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.

            • onabotulinumtoxinA

              donepezil increases and onabotulinumtoxinA decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • orphenadrine

              donepezil increases and orphenadrine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and donepezil both increase QTc interval. Use Caution/Monitor.

            • oxybutynin

              donepezil increases and oxybutynin decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oxybutynin topical

              donepezil increases and oxybutynin topical decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • oxybutynin transdermal

              donepezil increases and oxybutynin transdermal decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pancuronium

              donepezil increases and pancuronium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • paroxetine

              paroxetine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              donepezil and paroxetine both increase QTc interval. Use Caution/Monitor.

            • pasireotide

              donepezil and pasireotide both increase QTc interval. Use Caution/Monitor.

            • perphenazine

              donepezil and perphenazine both increase QTc interval. Use Caution/Monitor.

            • physostigmine

              donepezil and physostigmine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • pilocarpine

              donepezil and pilocarpine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • posaconazole

              donepezil and posaconazole both increase QTc interval. Use Caution/Monitor.

            • pralidoxime

              donepezil increases and pralidoxime decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • primaquine

              donepezil and primaquine both increase QTc interval. Use Caution/Monitor.

            • procainamide

              memantine will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • prochlorperazine

              donepezil and prochlorperazine both decrease QTc interval. Use Caution/Monitor.

            • promethazine

              donepezil and promethazine both decrease QTc interval. Use Caution/Monitor.

            • propantheline

              donepezil increases and propantheline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              donepezil increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              donepezil and protriptyline both increase QTc interval. Use Caution/Monitor.

            • pyridostigmine

              donepezil and pyridostigmine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • quinidine

              quinidine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              quinidine will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • ramelteon

              donepezil will increase the level or effect of ramelteon by unspecified interaction mechanism. Use Caution/Monitor. AUC and Cmax increased by 100% and 87% respectively.

            • sodium bicarbonate

              sodium bicarbonate will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • ranolazine

              donepezil and ranolazine both increase QTc interval. Use Caution/Monitor.

            • rapacuronium

              donepezil increases and rapacuronium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • rifabutin

              rifabutin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rilpivirine

              donepezil and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • risperidone

              donepezil and risperidone both increase QTc interval. Use Caution/Monitor.

            • rivastigmine

              donepezil and rivastigmine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • rocuronium

              donepezil increases and rocuronium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • romidepsin

              donepezil and romidepsin both increase QTc interval. Use Caution/Monitor.

            • salmeterol

              donepezil and salmeterol both increase QTc interval. Use Caution/Monitor.

            • scopolamine

              donepezil increases and scopolamine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sertraline

              donepezil and sertraline both increase QTc interval. Use Caution/Monitor.

            • sodium citrate/citric acid

              sodium citrate/citric acid will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • sodium lactate

              sodium lactate will increase the level or effect of memantine by passive renal tubular reabsorption - basic urine. Use Caution/Monitor.

            • solifenacin

              donepezil increases and solifenacin decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • St John's Wort

              St John's Wort will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • succinylcholine

              donepezil and succinylcholine both increase cholinergic effects/transmission. Use Caution/Monitor.

            • sunitinib

              donepezil and sunitinib both increase QTc interval. Use Caution/Monitor.

            • tacrolimus

              donepezil and tacrolimus both increase QTc interval. Use Caution/Monitor.

            • telavancin

              donepezil and telavancin both increase QTc interval. Use Caution/Monitor.

            • tenofovir DF

              tenofovir DF increases levels of memantine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • tiotropium

              donepezil increases and tiotropium decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tolterodine

              donepezil increases and tolterodine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triclabendazole

              donepezil and triclabendazole both increase QTc interval. Use Caution/Monitor.

            • trifluoperazine

              donepezil and trifluoperazine both decrease QTc interval. Use Caution/Monitor.

            • trihexyphenidyl

              donepezil decreases effects of trihexyphenidyl by pharmacodynamic antagonism. Use Caution/Monitor.

            • trimipramine

              donepezil increases and trimipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • triptorelin

              donepezil and triptorelin both increase QTc interval. Use Caution/Monitor.

            • trospium chloride

              donepezil increases and trospium chloride decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • umeclidinium bromide/vilanterol inhaled

              donepezil and umeclidinium bromide/vilanterol inhaled both decrease QTc interval. Use Caution/Monitor.

            • valbenazine

              valbenazine and donepezil both increase QTc interval. Use Caution/Monitor.

            • vandetanib

              vandetanib increases levels of memantine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

            • vardenafil

              donepezil and vardenafil both increase QTc interval. Use Caution/Monitor.

            Minor (141)

            • aclidinium

              donepezil decreases effects of aclidinium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • amiodarone

              amiodarone will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • amobarbital

              amobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anticholinergic/sedative combos

              donepezil decreases effects of anticholinergic/sedative combos by pharmacodynamic antagonism. Minor/Significance Unknown.

            • aprepitant

              aprepitant will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • armodafinil

              armodafinil will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • asenapine

              asenapine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • atazanavir

              atazanavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atracurium

              donepezil decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • atropine

              donepezil decreases effects of atropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • atropine IV/IM

              donepezil decreases effects of atropine IV/IM by pharmacodynamic antagonism. Minor/Significance Unknown.

            • belladonna alkaloids

              donepezil decreases effects of belladonna alkaloids by pharmacodynamic antagonism. Minor/Significance Unknown.

            • belladonna and opium

              donepezil decreases effects of belladonna and opium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • bethanechol

              donepezil increases effects of bethanechol by pharmacodynamic synergism. Minor/Significance Unknown.

            • bosentan

              bosentan will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • budesonide

              budesonide will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • bupropion

              bupropion will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • butabarbital

              butabarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • butalbital

              butalbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • carbachol

              donepezil increases effects of carbachol by pharmacodynamic synergism. Minor/Significance Unknown.

            • celecoxib

              celecoxib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cevimeline

              donepezil increases effects of cevimeline by pharmacodynamic synergism. Minor/Significance Unknown.

            • chloroquine

              chloroquine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • cisatracurium

              donepezil decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • conivaptan

              conivaptan will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cortisone

              cortisone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclizine

              donepezil decreases effects of cyclizine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • cyclobenzaprine

              donepezil decreases effects of cyclobenzaprine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • cyclosporine

              cyclosporine will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • darifenacin

              darifenacin will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              darifenacin will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              donepezil decreases effects of darifenacin by pharmacodynamic antagonism. Minor/Significance Unknown.

            • darunavir

              darunavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dasatinib

              dasatinib will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • deferasirox

              deferasirox will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desipramine

              donepezil increases and desipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • dexamethasone

              dexamethasone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dicyclomine

              donepezil decreases effects of dicyclomine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • diphenhydramine

              diphenhydramine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              donepezil decreases effects of diphenhydramine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • dronedarone

              dronedarone will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              dronedarone will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • duloxetine

              duloxetine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • echothiophate iodide

              donepezil increases effects of echothiophate iodide by pharmacodynamic synergism. Minor/Significance Unknown.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • etravirine

              etravirine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fesoterodine

              donepezil decreases effects of fesoterodine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • flavoxate

              donepezil decreases effects of flavoxate by pharmacodynamic antagonism. Minor/Significance Unknown.

            • fluconazole

              fluconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fosamprenavir

              fosamprenavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fosaprepitant

              fosaprepitant will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • galantamine

              donepezil increases effects of galantamine by pharmacodynamic synergism. Minor/Significance Unknown.

            • glycopyrrolate

              donepezil decreases effects of glycopyrrolate by pharmacodynamic antagonism. Minor/Significance Unknown.

            • glycopyrrolate inhaled

              donepezil decreases effects of glycopyrrolate inhaled by pharmacodynamic antagonism. Minor/Significance Unknown.

            • grapefruit

              grapefruit will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • griseofulvin

              griseofulvin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • haloperidol

              haloperidol will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • henbane

              donepezil decreases effects of henbane by pharmacodynamic antagonism. Minor/Significance Unknown.

            • homatropine

              donepezil decreases effects of homatropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • huperzine A

              donepezil increases effects of huperzine A by pharmacodynamic synergism. Minor/Significance Unknown.

            • hydrochlorothiazide

              hydrochlorothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hyoscyamine

              donepezil decreases effects of hyoscyamine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • hyoscyamine spray

              donepezil decreases effects of hyoscyamine spray by pharmacodynamic antagonism. Minor/Significance Unknown.

            • imatinib

              imatinib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • indinavir

              indinavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ipratropium

              donepezil decreases effects of ipratropium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of memantine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

            • isoniazid

              isoniazid will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lapatinib

              lapatinib will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lumefantrine

              lumefantrine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • maraviroc

              maraviroc will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              marijuana will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • meclizine

              donepezil decreases effects of meclizine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • metformin

              memantine will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methscopolamine

              donepezil decreases effects of methscopolamine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • methyclothiazide

              methyclothiazide will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • midodrine

              memantine will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • nefazodone

              nefazodone will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nelfinavir

              nelfinavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • neostigmine

              donepezil increases effects of neostigmine by pharmacodynamic synergism. Minor/Significance Unknown.

            • nevirapine

              nevirapine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              nifedipine will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              nilotinib will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ofloxacin

              memantine will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • onabotulinumtoxinA

              donepezil decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxybutynin

              donepezil decreases effects of oxybutynin by pharmacodynamic antagonism. Minor/Significance Unknown.

            • oxybutynin topical

              donepezil decreases effects of oxybutynin topical by pharmacodynamic antagonism. Minor/Significance Unknown.

            • oxybutynin transdermal

              donepezil decreases effects of oxybutynin transdermal by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pancuronium

              donepezil decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pantothenic acid

              pantothenic acid, donepezil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • phenobarbital

              phenobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • phenytoin

              phenytoin will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • physostigmine

              donepezil increases effects of physostigmine by pharmacodynamic synergism. Minor/Significance Unknown.

            • pilocarpine

              donepezil increases effects of pilocarpine by pharmacodynamic synergism. Minor/Significance Unknown.

            • posaconazole

              posaconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pralidoxime

              donepezil decreases effects of pralidoxime by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pramipexole

              memantine will increase the level or effect of pramipexole by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • prednisone

              prednisone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • procainamide

              procainamide decreases effects of donepezil by pharmacodynamic antagonism. Minor/Significance Unknown.

            • propafenone

              propafenone will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • propantheline

              donepezil decreases effects of propantheline by pharmacodynamic antagonism. Minor/Significance Unknown.

            • pyridostigmine

              donepezil increases effects of pyridostigmine by pharmacodynamic synergism. Minor/Significance Unknown.

            • quinacrine

              quinacrine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • quinine

              memantine will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • rapacuronium

              donepezil decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • rifapentine

              rifapentine will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ritonavir

              ritonavir will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              ritonavir will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rocuronium

              donepezil decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • rufinamide

              rufinamide will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • scopolamine

              donepezil decreases effects of scopolamine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sertraline

              sertraline will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • solifenacin

              donepezil decreases effects of solifenacin by pharmacodynamic antagonism. Minor/Significance Unknown.

            • succinylcholine

              donepezil increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • thioridazine

              thioridazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tiotropium

              donepezil decreases effects of tiotropium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • tipranavir

              tipranavir will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tolterodine

              donepezil decreases effects of tolterodine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • topiramate

              topiramate will decrease the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • trazodone

              donepezil increases and trazodone decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

            • triamterene

              memantine will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • trimethoprim

              memantine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • trospium chloride

              donepezil decreases effects of trospium chloride by pharmacodynamic antagonism. Minor/Significance Unknown.

            • vecuronium

              donepezil decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

            • venlafaxine

              venlafaxine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • verapamil

              verapamil will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              memantine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • voriconazole

              voriconazole will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zafirlukast

              zafirlukast will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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            Adverse Effects

            >10% (donepezil)

            Nausea (5-19%)

            Diarrhea (8-15%)

            Insomnia (5-14%)

            Accident (7-13%)

            Infection (11%)

            1-10% (memantine)

            Dizziness (7%)

            Confusion (6%)

            Headache (6%)

            Constipation (5%)

            Cough (4%)

            Hypertension (4%)

            Backache (3%)

            Pain (3%)

            Somnolence (3%)

            Syncope (3%)

            Vomiting (3%)

            Dyspnea (2%)

            Fatigue (2%)

            1-10% (donepezil)

            Headache (4-10%)

            Vomiting (3-8%)

            Cramping (3-8%)

            Fatigue (3-8%)

            Anorexia (3-7%)

            Hypertension (3% )

            Abnormal dreams (3%)

            Hallucinations (3%)

            Confusion (2%)

            Syncope (2%)

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            Warnings

            Contraindications

            Hypersensitivity to memantine, donepezil, or piperidine derivatives

            Cautions

            Memantine

            • Conditions that raise urine pH may decrease urinary elimination and increase plasma levels of memantine
            • Use caution in cardiovascular disease, seizure disorder, ophthalmic disease, hepatic and/or renal impairment

            Donepezil

            • Risk of GI bleed: Patients receiving therapy should be monitored closely for symptoms of active or occult gastrointestinal bleeding, especially those at increased risk for developing ulcers, eg, those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs)
            • Cholinesterase inhibitors are likely to exaggerate succinylcholine-type muscle relaxation during anesthesia
            • Syncopal episodes reported in association with use of donepezil
            • Cholinesterase inhibitors may have vagotonic effects on the sinoatrial and atrioventricular nodes manifesting as bradycardia or heart block
            • May cause diarrhea, nausea, and vomiting; effects have been mild and transient, sometimes lasting one to three weeks, and have resolved during continued use of donepezil hydrochloride; observe patients closely at the initiating of therapy
            • May cause anorexia and/or weight loss (dose dependent)
            • Cholinomimetics may cause bladder outflow obstructions
            • Cholinomimetics are believed to have some potential to cause generalized convulsions
            • Cholinesterase inhibitors should be prescribed with care with history of asthma or obstructive pulmonary disease
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            Pregnancy & Lactation

            Pregnancy Category: B (memantine); C (donepezil)

            Lactation: Unknown if distributed in human breast milk

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Memantine: Low- to moderate-affinity uncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist that binds preferentially to NMDAR-operated cation channels, blocking receptor only under conditions of excessive stimulation, with no effect on normal neurotransmission

            Donepezil: Acetylcholinesterase inhibitor that causes an increase in concentrations of acetylcholine, which in turn enhances cholinergic neurotransmission

            Absorption

            Peak plasma time (memantine ER): 18 hr (with food); 25 hr (fasting)

            Distribution

            Protein bound (memantine ER): 45%

            Vd (memantine ER): 9-11 L/kg

            Metabolism

            Memantine: Undergoes partial hepatic metabolism; CYP450 enzyme system does not play a significant role

            Elimination

            Half-life (memantine): 60-80 hr

            Excretion (memantine): Predominantly in urine (48% unchanged); renal clearance involves active tubular secretion moderated by pH dependent tubular reabsorption

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            Administration

            Oral Administration

            May take with or without food

            Capsules can be taken intact or may be opened, sprinkled on applesauce, and swallowed without chewing

            The entire contents of each capsule should be consumed; the dose should not be divided

            Except when opened and sprinkled on applesauce, the capsule should be swallowed capsule whole; do not divide, chew, or crush

            Missed dose: If patient misses a single dose, the next dose should be taken as scheduled, without doubling up the dose

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.