Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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)
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
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
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.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
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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