donepezil transdermal (Rx)

Brand and Other Names:Adlarity

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

transdermal system

  • 5mg/day
  • 10mg/day

Alzheimer Dementia

Indicated for treatment of mild, moderate, and severe Alzheimer dementia

Apply 5 mg/day patch once weekly initially; may increase dosage to 10 mg/day patch once weekly after 4-6 weeks

Doses >10 mg/day have not been evaluated

Dosage Modifications

Renal impairment: No dosage adjustment necessary

Hepatic impairment

  • Patients with stable alcoholic cirrhosis had a decrease in donepezil clearance by 20% compared with 10 healthy age- and sex-matched subjects

Dosing Considerations

Switching to transdermal system from tablets or oral disintegrating tablets

  • Currently on 5 mg/day PO: Switch to once weekly 5 mg/day transdermal system
  • Currently on 5 mg/day PO for at least 4-6 week: May switch immediately to once weekly 10 mg/day transdermal system
  • Currently on 10 mg/day PO: Switch to once weekly 10 mg/day transdermal system
  • Instruct patients or caregivers to apply first transdermal system with last administered oral dose

Safety and efficacy not established

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Interactions

Interaction Checker

and donepezil transdermal

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (1)

              • fexinidazole

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

              Monitor Closely (71)

              • aclidinium

                donepezil transdermal, aclidinium. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • atracurium

                donepezil transdermal and atracurium both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              • atropine

                donepezil transdermal, atropine. Either decreases effects of the other by pharmacodynamic antagonism. Modify Therapy/Monitor Closely.

              • atropine ophthalmic

                donepezil transdermal, atropine ophthalmic. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • brompheniramine

                donepezil transdermal, brompheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • carbinoxamine

                donepezil transdermal, carbinoxamine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • cetirizine

                donepezil transdermal, cetirizine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • chlorpheniramine

                donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • chlorpromazine

                donepezil transdermal, chlorpromazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • cisatracurium

                donepezil transdermal and cisatracurium both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              • clemastine

                donepezil transdermal, clemastine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • cyclobenzaprine

                cyclobenzaprine, donepezil transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • cyproheptadine

                donepezil transdermal, cyproheptadine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • darifenacin

                donepezil transdermal, darifenacin. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • desloratadine

                donepezil transdermal, desloratadine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • dexchlorpheniramine

                donepezil transdermal, dexchlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • dicyclomine

                donepezil transdermal, dicyclomine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • dimenhydrinate

                donepezil transdermal, dimenhydrinate. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • diphenhydramine

                donepezil transdermal, diphenhydramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • fesoterodine

                donepezil transdermal, fesoterodine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • fexofenadine

                donepezil transdermal, fexofenadine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • flavoxate

                donepezil transdermal, flavoxate. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • fluphenazine

                donepezil transdermal, fluphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • glycopyrrolate

                donepezil transdermal, glycopyrrolate. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • glycopyrrolate inhaled

                donepezil transdermal, glycopyrrolate inhaled. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • glycopyrronium tosylate topical

                donepezil transdermal, glycopyrronium tosylate topical. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • haloperidol

                donepezil transdermal, haloperidol. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • homatropine

                donepezil transdermal, homatropine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • hydroxyzine

                donepezil transdermal, hydroxyzine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • hyoscyamine

                donepezil transdermal, hyoscyamine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • hyoscyamine spray

                donepezil transdermal, hyoscyamine spray. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • ipratropium

                donepezil transdermal, ipratropium. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • isocarboxazid

                donepezil transdermal, isocarboxazid. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • levocetirizine

                donepezil transdermal, levocetirizine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • loratadine

                donepezil transdermal, loratadine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • loxapine

                donepezil transdermal, loxapine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • loxapine inhaled

                donepezil transdermal, loxapine inhaled. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • meclizine

                meclizine, donepezil transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • mepenzolate

                donepezil transdermal, mepenzolate. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • methscopolamine

                donepezil transdermal, methscopolamine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • molindone

                donepezil transdermal, molindone. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • oxybutynin

                donepezil transdermal, oxybutynin. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • oxybutynin topical

                donepezil transdermal, oxybutynin topical. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • oxybutynin transdermal

                donepezil transdermal, oxybutynin transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • pancuronium

                donepezil transdermal and pancuronium both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              • perphenazine

                donepezil transdermal, perphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • phenelzine

                donepezil transdermal, phenelzine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • pimozide

                donepezil transdermal, pimozide. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • prochlorperazine

                donepezil transdermal, prochlorperazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • promethazine

                donepezil transdermal, promethazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • propantheline

                donepezil transdermal, propantheline. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • quetiapine

                quetiapine, donepezil transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • quinidine

                quinidine, donepezil transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • revefenacin

                donepezil transdermal, revefenacin. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • ribociclib

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

              • risperidone

                risperidone, donepezil transdermal. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • rocuronium

                donepezil transdermal and rocuronium both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              • scopolamine ophthalmic

                donepezil transdermal, scopolamine ophthalmic. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • solifenacin

                donepezil transdermal, solifenacin. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • succinylcholine

                donepezil transdermal and succinylcholine both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              • thioridazine

                donepezil transdermal, thioridazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • thiothixene

                donepezil transdermal, thiothixene. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • tiotropium

                donepezil transdermal, tiotropium. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • tolterodine

                donepezil transdermal, tolterodine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • tranylcypromine

                donepezil transdermal, tranylcypromine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • trifluoperazine

                donepezil transdermal, trifluoperazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • triprolidine

                donepezil transdermal, triprolidine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • trospium chloride

                donepezil transdermal, trospium chloride. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • umeclidinium bromide

                donepezil transdermal, umeclidinium bromide. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • umeclidinium bromide/vilanterol inhaled

                donepezil transdermal, umeclidinium bromide/vilanterol inhaled. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

              • vecuronium

                donepezil transdermal and vecuronium both increase pharmacodynamic synergism. Use Caution/Monitor. Donepezil transdermal, a cholinesterase inhibitor, may potentiate the effects on muscle relacation during anesthesia.

              Minor (0)

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                Adverse Effects

                Refer to donepezil tablets monograph for adverse reactions

                >10%

                Erythema (64.6%)

                Papules (16%)

                Headache (15%)

                1-10%

                Application site pruritus (9%)

                Muscle spasms (9%)

                Insomnia (7%)

                Abdominal pain (6%)

                Application site dermatitis (6%)

                Constipation (6%)

                Diarrhea (4%)

                Application site pain (4%)

                Dizziness (4%)

                Abnormal dreams (4%)

                Skin laceration (4%)

                <1%

                Edema (0.4%)

                Postmarketing Reports

                Blood and lymphatic system disorders: Hemolytic anemia

                Cardiac disorders: Heart block (all types), QTc prolongation, and torsade de pointes

                Gastrointestinal disorders: Abdominal pain

                Hepatobiliary disorders: Cholecystitis, hepatitis, pancreatitis

                Metabolism and nutritional disorders: Hyponatremia

                Musculoskeletal and connective tissue disorders: Rhabdomyolysis

                Nervous system disorders: Convulsions, neuroleptic malignant syndrome

                Psychiatric disorder: Agitation, aggression, confusion, hallucinations

                Skin and subcutaneous tissue disorders: Rash

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                Warnings

                Contraindications

                Hypersensitivity to donepezil or piperidine derivatives

                History of allergic contact dermatitis with use

                Cautions

                Donepezil may potentiate succinylcholine-type muscle relaxation during anesthesia

                Cholinesterase inhibitors, including donepezil, may have vagotonic effects on sinoatrial and atrioventricular nodes, which may manifest as bradycardia or heart block in patients both with and without known underlying cardiac conduction abnormalities

                May cause diarrhea, nausea, and vomiting; in majority of cases, these effects have been transient, sometimes lasting 1-3 weeks, and resolve with continued use; closely monitor when initiating and after dose increases

                May increase gastric acid secretion due to increased cholinergic activity; closely monitor for symptoms of active or occult gastrointestinal bleeding, especially in patients at increased risk for developing ulcers (eg, history of ulcer disease or concomitant use of nonsteroidal anti-inflammatory drugs [NSAIDs]).

                Although not observed in clinical trials of donepezil tablets or transdermal systems, cholinomimetics, may cause bladder outflow obstruction

                Cholinomimetics are believed to have some potential to cause generalized convulsions; however, seizure activity also may be a manifestation of Alzheimer disease

                Caution with a history of asthma or obstructive pulmonary disease

                Application-site skin reactions

                • Skin application-site reactions have occurred; use may lead to allergic contact dermatitis
                • Allergic contact dermatitis should be suspected if application-site reactions spread beyond the size of the transdermal system, if there is evidence of a more intense local reaction (eg, increasing erythema, edema, papules, vesicles), and if symptoms do not significantly improve within 48 hr after transdermal system removal

                Drug interaction overview

                • Anticholinergics
                  • Owing to mechanism of actions, donepezil transdermal may potentially interfere with activity of anticholinergic medications
                • Cholinomimetics and other cholinesterase inhibitors
                  • Coadministration with succinylcholine, similar neuromuscular blocking agents, or cholinergic agonists (eg, bethanechol) may cause a synergistic effect on muscle relaxation
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                Pregnancy & Lactation

                Pregnancy

                No adequate data are available on developmental risks associated with use in pregnant females

                Animal data

                • Oral donepezil administered to pregnant rats and rabbits during organogenesis resulted in no adverse developmental effect; highest doses (16 and 10 mg/kg/day, respectively) were approximately 16x and 19x, respectively, at the maximum recommended human dose
                • Oral donepezil (1, 3, 10 mg/kg/day) administered to rats during late gestation and throughout lactation to weaning resulted in increased stillbirths and offspring mortality at the highest dose tested

                Lactation

                There are no data on presence of donepezil or its metabolites in human milk, effects on breastfed infants, or on milk production

                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

                Reversible acetylcholinesterase inhibitor; increases acetylcholine concentrations, which in turn enhances cholinergic neurotransmission

                There is no evidence that donepezil alters the course of underlying dementing process

                Absorption

                Steady-state reached at 22 days (after 3 weeks)

                Application to thighs and buttocks showed a 14-18% lower AUCinf and a 21-24% higher peak plasma concentration compared to application on the back

                Mean plasma donepezil concentration profiles showed transitory increases (up to 60% increase in the partial AUC corresponding to heat application periods) during heat sessions compared with control conditions

                Distribution

                Protein bound: 96%; mainly albumin (~75%)

                Vd (steady-state): 12-16 L/kg

                Metabolism

                Metabolized by CYP2D6 and CYP3A4 and undergoes glucuronidation

                Active metabolite: 6-O-desmethyl donepezil reported to inhibit acetylcholinesterase to same extent as donepezil in vitro

                Elimination

                Half-life: 91 hr

                Clearance: 0.12 L/hr/kg

                Excretion: 57% (urine); 15% (feces)

                Pharmacogenomics

                Effect of CYP2D6 genotype in patients with Alzheimer dementia showed differences in clearance values among subgroups

                Poor CYP2D6 metabolizers: 31.5% slower clearance

                Ultra-rapid CYP2D6 metabolizers: 24% faster clearance

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                Administration

                Transdermal Preparation

                Remove 1 transdermal system from refrigerator and allow pouch to reach room temperature before opening; do not use external heat sources to warm

                Do not apply a cold transdermal system

                Use within 24 hr of removing from refrigerator

                Ensure pouch seal has not been broken; discard if damaged, cut, or altered in any way

                Recommended application sites

                • Back (avoiding the spine); if needed, may use upper buttocks or upper outer thigh
                • DO NOT
                  • Use locations that will be rubbed by tight clothing
                  • Use the same location of an application site for at least 2 weeks (14 days) after removing transdermal system from that location
                  • Apply to areas on skin where medication, cream, lotion, or powder have recently been applied
                  • Apply to skin that is red, irritated, or cut
                  • Shave site of application

                Transdermal Administration

                Apply 1 transdermal system to skin once weekly

                Each transdermal system delivers either 5 mg or 10 mg of donepezil daily for 7 days (1 week cycle)

                At end of 7 days, remove used transdermal system and apply a new transdermal system (to different site); apply only 1 transdermal system at a time

                Apply to skin immediately after removing from pouch

                Apply to clean, dry, intact healthy skin with no to minimal hair

                Press down firmly for 30 seconds to ensure good contact with skin at edges of transdermal system.

                Use does not need to be interrupted due to bathing or hot weather.

                Avoid long exposure to external heat sources (eg, excessive sunlight, saunas, solariums, heating pads)

                Instruct patients and caregivers to avoid eye contact and to wash their hands after handling the transdermal system

                If accidental contact with the eyes occurs or if their eyes become red after handling the transdermal system, advise to rinse immediately with plenty of water and to seek medical advice if symptoms do not resolve

                Missed dose

                • If transdermal system falls off or if dose missed, apply new transdermal system immediately and then replace this transdermal system 7 days later to start a new 1-week cycle

                Storage

                Refrigerate at 2-8ºC (36-46ºF); do not freeze

                Use within 24 hr of removing from refrigerator

                Allow pouch to reach room temperature before opening and removing new transdermal system for application

                Keep in individually sealed pouch until use

                Fold used transdermal systems with adhesive surfaces pressed together and discard in trash; do not flush down toilet

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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.
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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.